breast cancer awareness research paper

• Open access
• Published: 02 October 2017

Awareness and current knowledge of breast cancer

• Muhammad Akram 1 ,
• Mehwish Iqbal 2 ,
• Muhammad Daniyal 2 &
• Asmat Ullah Khan 3 , 4  

Biological Research volume  50 , Article number:  33 ( 2017 ) Cite this article

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Breast cancer remains a worldwide public health dilemma and is currently the most common tumour in the globe. Awareness of breast cancer, public attentiveness, and advancement in breast imaging has made a positive impact on recognition and screening of breast cancer. Breast cancer is life-threatening disease in females and the leading cause of mortality among women population. For the previous two decades, studies related to the breast cancer has guided to astonishing advancement in our understanding of the breast cancer, resulting in further proficient treatments. Amongst all the malignant diseases, breast cancer is considered as one of the leading cause of death in post menopausal women accounting for 23% of all cancer deaths. It is a global issue now, but still it is diagnosed in their advanced stages due to the negligence of women regarding the self inspection and clinical examination of the breast. This review addresses anatomy of the breast, risk factors, epidemiology of breast cancer, pathogenesis of breast cancer, stages of breast cancer, diagnostic investigations and treatment including chemotherapy, surgery, targeted therapies, hormone replacement therapy, radiation therapy, complementary therapies, gene therapy and stem-cell therapy etc for breast cancer.

Breast cancer is the most common cancer and also the primary cause of mortality due to cancer in female around the World. About 1.38 million new breast cancer cases were diagnosed in 2008 with almost 50% of all breast cancer patients and approximately 60% of deaths occurring in developing countries. There is a huge difference in breast cancer survival rates worldwide, with an estimated 5-year survival of 80% in developed countries to below 40% for developing countries [ 1 ]. Developing countries face resource and infrastructure constraints that challenge the objective of improving breast cancer outcomes by timely recognition, diagnosis and management [ 2 ]. In developed countries like the United States, about 232,340 female will be diagnosed and death of 39,620 female will occur due to breast cancer in 2013 [ 3 ]. The lifetime risk of developing breast cancer in an American female is 12.38% [ 3 ]. The significant decline in morality due to breast cancer in the United States from 1975 to 2000 is attributed to constant enhancement in both screening mammography and management [ 4 ]. According to the World Health Organization (WHO), enhancing breast cancer outcome and survival by early detection remains the foundation of breast cancer regulations. Different modern medicines are prescribed to treat breast cancer. Medical therapy of breast cancer with antiestrogens such as raloxifene or tamoxifen might avoid breast cancer in individuals who are at increased possibility of developing it [ 5 ]. Surgery of both breasts is an added preventative measure in some increased probability of developing cancer in female. In patients who have been identified with breast tumor, different strategies of management are used such as targeted therapy, hormonal therapy, radiation therapy, surgery and chemotherapy. In individuals with distant metastasis, managements are typically aimed at enhancing life quality and survival rate [ 6 ]. The unpleasant side effects of breast cancer treatment are one of the most motivating factors to find some alternative methods. The use of herbs for treating the patients having breast cancer is considered a natural alternative, because some plants may contain properties that naturally have the ability to treat breast cancer [ 7 , 8 , 9 , 10 , 11 ].

Epidemiology

Currently, one in twelve females in Britain between age of 1 and 85 years gets breast cancer. With one million new cases of cancers reported in the World, breast cancer is common in females and comprises 18% of all women cancer. Incidence of breast cancer is predicted to increase to 85 per 100,000 women by 2021 [ 12 ]. In 2012, 1.67 million new cases of breast cancer were diagnosed that is 25% of all cancers among women. Ferlay et al. [ 13 ] stated that 883,000 cases are in less developed countries and 794,000 in most developed countries. According to the data, 145.2 women in Belgium and 66.3 in Poland between 100,000 suffer from breast cancer [ 14 ]. Incidence of breast cancer in the United States is one out of eight women and In Asia one woman suffers from breast cancer out of 35. In Iran, there are 10 cases in 100,000 populations and 7000 new cases have been reported annually [ 15 ]. Prevalence of breast cancer is increasing in Pakistan [ 16 , 17 , 18 ]. Breast cancer is found mostly in highly populated areas of South Asian developing counties [ 19 , 20 ]. Breast cancers in males have been detected in Northern areas of Pakistan [ 21 ]. Yang et al. [ 22 ] stated that new cases of breast cancer in China were 168,013 in 2005 and 121,269 in 2000.

Anatomy of breast

Both males and females have breasts [ 23 ]. The breast is made up of fatty tissue called adipose tissue [ 24 ]. The female’s breasts usually contain more glandular tissue than that of the males [ 25 ]. Female breasts contain 12–20 lobes which are further divided into smaller lobules [ 26 ]. These lobes and lobules are connected via milk ducts. The adipose tissue of the breast is supplied by a network of nerves, blood vessels, lymph vessels, lymph nodes, and is also composed of fibrous connective tissue and ligaments [ 27 ]. The female breast is designed to provide optimal nourishment for babies and to provide sexual pleasure for the female herself. The breasts are glandular organs that are very sensitive to hormonal changes in the body [ 28 ]. They adopt cyclic changes in synchrony with the menstrual cycle. They are closely associated with the genital system of females. Nipple stimulation enhances secretion of prolactin from the pituitary gland. This hormone also affects the uterus and can cause contractions. Lymph node draining the breast tissues is also found in the armpits. After a female has had a baby and her milk comes in, mother may develop striking swelling under arms from engorgement of the breast tissue in that region. Breasts come in all sizes and shapes, as do nipples. Most female possess one breast that slightly smaller than the other [ 29 ]. The epidermis of the areola and nipple is very much pigmented and to some extent wrinkled, and the nipple skin contains several apocrine and sebaceous sweat glands and somewhat small hair. The 15–25 milk ducts go into the base of the nipple, wherever they expand to synthesize the milk sinuses. These milk ducts functions as the carriers of milk towards the nipples [ 30 ]. Slightly under the surface of nipple, these sinuses end in cone-shaped ampullae. The spherical areola is present around the nipple and is between 15 and 60 mm in diameter. Sebaceous glands, sweat glands and lanugo hairs are present on its skin, Montgomery’s glands, are big, modified sebaceous glands with tiny milk ducts that open into Morgagni’s tubercles in the areola epidermis. Deep in the nipple and areola, several smooth muscle fibers are set circularly and radially in the dense connective tissue and longitudinally alongside the lactiferous ducts that lengthen up into the nipple. These muscle fibers are cause emptying of milk sinuses, nipple erection and contraction of areola. The greater part of the breast parenchyma expand inferiorly from the point of the 2nd or 3rd rib to the inframammary fold, which is at about the point of the 6th or 7th rib, and crossways from the border of the sternum to the anterior axillary line. The mammary tissue also expands erratically into the axilla as the glandular tail of spence. The posterior surface of the breast rests on segment of the fasciae of the pectoralis major, rectus abdominis muscles, external abdominal oblique and serratus anterior.

A global prospective

Globalization, which thus greatly characterizes our period, was primarily linked with commercial-related actions, consequently with ecological concerns, and especially in recent times with the dark truth of terrorism. Up till now the “globalization” of numerous human being actions, together with health care, has been departing on for several decades, enhancing in step with improvement in information machinery. Correctly or incorrectly, and whether planned or not, numerous clinicians in developing countries keep an eye on what Americans are achieving, or are alleged to be achieving, as “state of the art” and recent most excellent performance that ought to be copied. The actions reviewed and our current narration with transplantation of bone marrow recommends that present “standard of care” United States described interventions are inappropriate to global utilization. Unluckily, extensive deficiency of community wellbeing strategies to breast cancer has made understanding of such rights for females not viable. Impractical, deadly, and extremely expensive treatments for breast cancer cannot assist the huge number of females in the earth at danger for or who develop breast cancer [ 31 ].

Types of breast cancer

According to site, it is divided into invasive and non-invasive breast cancers

Non-invasive breast cancer

It is a cancer that has not extended away from the lobule or ducts where it situated [ 32 ]. An example of a kind of non-invasive breast cancer is ductal carcinoma in situ. Ductal carcinoma in situ appears when atypical cells develop within the milk ducts, however have not extended to close proximity of tissue or outside. The word “in situ” describes “in place.” Even though the atypical cells have not extended to tissues outer the lobules or ducts, they can progress and grow into invasive breast cancer. The normal background of every scientific unit is demonstrated and a biological understanding of the accessible information is presented. Lobular carcinoma in-situ is understood merely a risky sign moderately than a predecessor for the successive growth of invasive cancer, so that one time the judgment is made, additional operative involvement is avoidable and sequential follow-up only is suggested. The management of ductal carcinoma in-situ should be kept in mind that breast-preserving treatment is at the present considered best therapy of breast cancer, the illness we are attempting to stop [ 33 ]. The pitfalls of suggested management based on retrospective statistics are have been taken into account and the requirement to conduct clinical studies intended to establish the best possible beneficial treatment of non-invasive breast cancer is affirmed [ 34 ].

Lobular carcinoma in situ (LCIS)

This type of breast cancer develops into breast lobules [ 35 ]. The breast cancer has not extended exterior to the lobules into the breast tissue [ 36 ]. Lobular carcinoma in situ is usually identified as non-invasive breast cancer [ 37 ].

Ductal carcinoma in situ

It is the most general kind of non-invasive breast cancer, is limited to the breast duct. Example of ductal carcinoma in situ is ductal comedocarcinoma [ 38 ].

Invasive breast cancer

It exists when abnormal cells from within the lobules or milk ducts split out into close proximity of breast tissue [ 39 ]. Cancer cells can pass through the breast to different parts of the body through immune system or the systemic circulation [ 40 ]. They may move early in the development when the tumor is a minute or afterward when the tumor is huge Invasive breast cancer is most occurring general carcinoma in females. The regions of elevated threat are the prosperous populations of Australia and Europe wherever 6% of females suffer from invasive breast cancer prior to 75 years of age. The prevalence of breast cancer enhances quickly with increasing age [ 41 ]. Invasive breast cancer that extends to different organs of the body is also recognized as metastatic breast cancer [ 42 ]. Most common organ to which these cells spread are brain, bones, lungs and liver. These cells once more segregate and expand irregularly and produce new cancers. The new forming cells are developing in different part of the body, it is still breast cancer [ 43 ].

Infiltrating lobular carcinoma (ILC)

Infiltrating lobular carcinoma is also recognized as invasive lobular carcinoma. ILC originates in the milk glands (lobules) of the breast, but frequently extends to other areas of the body [ 44 ].

Infiltrating ductal carcinoma

Infiltrating ductal carcinoma is also recognized as invasive ductal carcinoma. IDC originates in the milk ducts of the breast and extends to the duct wall, invading the breast fatty tissues and probably other parts of the body [ 45 ].

Medullary carcinoma

Medullary carcinoma is an invasive breast cancer that designs a discrete margin normal tissue and medullary tissue [ 46 ].

Mucinous carcinoma

It is recognized as colloid carcinoma , mutinous carcinoma is a uncommon breast cancer created by the mucus-forming cancer cells. Females with mutinous carcinoma usually have an improved prediction than females with additional general kinds of invasive carcinoma [ 47 ].

Tubular carcinoma

Tubular carcinomas are a particular kind of invasive breast carcinoma. Females with tubular carcinoma usually have an improved prospects than women with additional general kinds of invasive carcinoma [ 48 ].

Inflammatory breast cancer

Inflammatory breast cancer is the form of swollen breasts (red and warm) with dimples and/or broad ridges due to cancer cells blocking lymph vessels or channels in the skin over the breast. Though inflammatory breast cancer is uncommon and is tremendously fast-growing [ 49 ]. Treatment involves vigilant synchronization of all multidisciplinary strategies, including radiation therapy, surgery, chemotherapy and imaging. The administration of neoadjuvant chemotherapy has accorded considerably to enhancement in general survival from the time when the earliest report of this matter and has performed the function of locoregional treatment such as radiation and surgery significant to sustained improvements in this ailment [ 50 ].

Paget’s disease of the breast

It is the uncommon type of breast cancer that usually shows visible changes to the nipple of the breast [ 51 ]. Its symptoms include red itchy rashes involving the nipple and then it can sometime spread to the normal skin as well. However it resembles with the other skin conditions such as eczema and psoriasis but it can be differentiated as the other skin conditions usually affects both the breasts and can start from the areola rather than the nipple of the breast however Paget’s disease of the breast most often affects only one breast and starts with the nipple of the breast instead of areola (breastcancercare.org.uk) Nearly 1–3% of all the breast cancers are Paget’s disease and can affect both men as well as women. The actual theory behind the pathogenesis or development of Paget’s disease of the breast isn’t clear yet however there are few theories supporting it’s pathogenesis. Their warning signs include bleeding and oozing of discharge from the nipple, flattening or inversion of nipple, lump found in the breast etc. It can be diagnosed by using punch biopsy. It’s prognosis is good if it remains within the nipple or in ducts of the breast [ 52 ].

Phyllodes tumor

Phyllodes tumors are can be either benign or malignant [ 53 ]. Phyllodes tumors develop in the connective tissues of the breast and may be treated by surgical removal [ 54 ]. Phylloides tumors are extremely uncommon; fewer than 10 females die of this kind of breast cancer every year in the United States [ 55 ].

Triple-negative breast cancer

Breast cancer is at the present extensively documented that is a heterogeneous disorder with special sub-forms, distinguished by means of their dissimilar clinico-pathological characteristics, prevision and responses to management. Triple-negative breast cancer is described by the deficiency of progesterone receptor, human epidermal growth factor receptor 2 and estrogen receptor expression [ 56 ]. This type is mainly destructive, commonly observed in premenopausal females, and is responsible for 10–15% of cases in white females, with a elevated occurrence [ 57 ].

Pathogenesis of breast cancer

The breast is a complex tubulo-alveolar organ fixed within an asymmetrical connective tissue [ 58 ], that go through a chain of alteration from child bearing age to senility. The changes seen with every menstrual cycle and pregnancy guided us to assume the occurrence of precursor cells in the mature tissue that is able of synthesizing novel duct-lobular units [ 59 ]. The typical breast architecture contains a stratified epithelium bordered by a basement membrane and fixed in a template of blood vessels, lymphatic and stromal cells [ 60 ]. In the usual breast, the stratified epithelium comprised of two dissimilar cell populations, myoepithelial and epithelial, which can be distinguished by way of immunohistochemical staining with antibodies against myosin and CK, correspondingly. It has been postulated that the creation of cellular heterogeneity in breast disorders depends on the primary developmental series of the usual breast. This heterogenicity of the breast carcinoma might happen from the neoplastic change of either myoepithelial or epithelial cell, or yet from a stem cell that has the ability to develop into myoepithelial or epithelial cells [ 61 ]. According to the oncology of breast cancer, neoplastic cells differ from the normal body cells. Normal tissues of the body have limited growth promotion and regulation which helps to keep the structure and functions of tissues usual. However, cancerous cells have prolonged and chronic proliferation without any external stimuli [ 62 ]. Cancer cells overcome the growth suppressor genes [ 63 ]. Breast cancer is a malignant disease that initiates in the breast cells. Like other malignant tumors, there are numerous causes that can increase the possibility of developing breast cancer. Injure to the deoxyribonucleic acid (DNA) and hereditary alteration can guide to breast cancer have been associated with the exposure of estrogen. Some patients inherit fault in the deoxyribonucleic acid (DNA) and genes like the P53, BRCA1 and BRCA2 among others. The patients with a family history of breast or ovarian cancer have possibility of developing breast cancer [ 64 ]. Neoplastic cells require considerable potential to multiply and convert into a massive tumor [ 65 ]. The immune system usually tries to find out cancer cells and cells with injured deoxyribonucleic acid (DNA) and demolish them. Breast cancer might be outcome of malfunction of such an useful immune defence and surveillance. Breast cancer commonly occurs due to an association between genetic and environmental factors. RAS/MEK/ERK pathway and PI3K/AKT pathway defend normal cells from cell suicide. When mutation occurs in genes that are involved in encoding of these protective pathways, the cells become unable of committing suicide when they are no longer required which then leads to development of cancer. These mutations were confirmed to be experimentally associated with estrogen exposure [ 66 ]. It was recommended that deformity in the growth factors signaling can assist growth of malignant cells. Over expression of leptinin breast adipose tissue enhances proliferation of cell and cancer [ 67 ]. These are numerous growth factors signaling and other factors that interrelate between epithelial cells and stromal cells. Interruption in these might result in development of breast cancer. In cancer cells, enzyme telomerase turns away the chromosomal shortening and allows the extensive replication of cells [ 68 ]. Tumor cells get their nutrients and oxygen supply by angiogenesis [ 69 ]. Cancer cells break their boundaries and can enter into the blood, lymphatic tissues and other tissues of the body to produce a secondary tumor [ 70 ].

Causative factors and associated risks of breast carcinoma

Breast cancer is the leading cause of death among British females who are 40–55 years of age. Breast cancer is more common in single women than in married women [ 71 , 72 ]. The breast is an estrogen sensitive organ. Many females who have been on birth control pills or estrogen replacement have found that the medications result in enlarged and often tender breasts. The activity of this medication, combined with the standard western high fat, low fiber diet, which over-stimulates breast tissue, could be a trigger for breast cancer. Incidence of breast cancer is higher in women above 50 years of age and 2 cases per 1000 are reported in this age group. Epidemiological investigations have also suggested that those women who have many children possess lower risk of breast cancer than those women who have fewer children. Incidence of breast cancer is 10.04% among all cancers and, most commonly occurs in 40–50 aged women. Mean age of breast cancer in Iranian women is 48 years [ 73 ]. An association of clinic pathological characteristic and breast cancer subtypes has been determined in Iranian women [ 74 ]. Breast cancer mostly occurs in obese women [ 75 ]. Depression is most commonly found in women with breast cancer [ 76 ]. Andsoy et al. [ 77 ] conducted a study to investigate knowledge of colorectal, cervical and breast cancer. For this study 226 working nurses were screened. It is very interesting that certain epidemiological studies have claimed that women who give birth to their child before they attain the age of 20 years are known to have decreased risk of breast cancer than those women who have not given birth to any child or who have given birth to their first child after the age of 30 years. The risk increases with age rapidly during premenopausal and slowly during post-menopausal life. Breast feeding decreases the risk of breast cancer [ 78 ]. Menopause resulting from surgical removal of ovaries (oophorectomy) decreases the risk [ 79 ]. Presence of certain kinds of benign tumours in breast increases the risk of malignancy [ 80 ]. The ovaries stop producing the female hormones once the menopause sets in, but in obese women the fatty tissue can provide the estrogen as it is capable of producing it. This increase in hormone production seems to increase the risk of breast cancer in obese post menopausal women. Deficiency of vitamin D and lack of sun exposure is considered to be the important cause of breast cancer [ 81 ]. It is found to be more in women than men [ 82 ]. The risk of breast cancer increases with age however rarely found before the age of 20 years [ 83 ]. Carcinoma in one breast can increase the risk by four times in another breast. While the patients that have the history of ovarian, endometrial or colon cancer have 1–2 times increased risk to develop breast carcinoma [ 84 ]. A female who has had breast cancer has an enhanced danger of occurring breast cancer in the other breast [ 85 ]. The minimal role of the gene has been established in the development of breast cancer. BRCA-1 (breast cancer susceptibility gene) is considered to be the cause of 5–10% of breast cancer that is transferred from either father or mother to the next generation. The study indicates that right environmental conditions are required for cancer promoting gene for expression. Certain families have been recognized with a genetically higher incidence of early onset breast cancer. If some individuals of the female’s family have had a specific kind of cancer, female may have an enhanced danger risk of breast cancer [ 86 ]. The danger is maximum if the affected family member had breast cancer at a juvenile period, had cancer in both breasts, or if female is a close family member. First-degree family members such as daughter, sister and mother are mainly significant in estimating threat. Numerous second-degree relatives such as an aunt and grandmother with breast cancer might also enhance threat. Breast cancer in a male enhances the danger for the entire close female relatives. Women who have a positive family history of breast carcinoma are 2–4 times more likely to develop the cancer, especially the females who are the carriers of BRCA1 or BRCA2 genes have the significant chance to develop carcinoma of breast [ 87 ]. Breast cancer affects both male and females; though, the prevalence is more in female as compared to male. Generally, females are at 100-fold increased danger of breast cancer than male [ 88 ]. Early menarche, nulli parity, pregnancy after the age of 30, oral contraceptives or hormone replacement therapy all these factors can increase the risk of breast cancer [ 83 ]. Steroid hormones include androgens, progesterone and estrogen, which belong to a cluster of structurally connected hormones known as sex hormones that are released into the blood by the gonads and adrenal glands. They are synthesized from single general precursor, cholesterol through a reaction catalyzed by numerous enzymes to make a large diversity of hormones for diverse target organs and tissues [ 89 ]. This procedure is well regulated and the discharge of these hormones into the systemic circulation. These hormones cross the plasma membrane to reach the target cells and bind to specific receptors called steroid hormone receptors to exert their activity [ 90 ]. Oestrogens have important activities on differentiation, growth and performance of several tissues, including urogenital system of man and women, cardiovascular system, brain, uterus and breast [ 89 ]. In accordance with this, Kato et al. [ 91 ], reported that the progression of reproductive organ cancer like prostate and breast cancer frequently occurs because of the androgens, progesterone and estrogen, which exert numerous biological activities in normal as well as abnormal cells. The study indicates that the development of normal and abnormal epithelial cells of the breast can be modulated by stromal cells of the breast and can release growth factors after stimulation by the endogenous hormones. An aromatase enzyme is found in adipose tissues, which makes estradiol from the precursor molecule, cholesterol. Fat cells are found in excess amount in breast of aged females; therefore, the quantity of estradiol is higher in breast tissues of post menopausal female than their plasma level [ 92 ]. This most likely is responsible for the increasing occurrence of breast cancer in aged female and assists the action of steroid hormones in breast cancer pathogenesis. Benign tumors and proliferative lesions without or with atypia can increase the risk of breast cancer [ 85 ]. Breast cancer has been linked with high level of dietary fats and low level of certain nutrients for various years [ 93 ]. Animal fat stimulates colonal bacterial to form estrogen from cholesterol found in the diet, thus increasing level of estrogen in the body. The body fat is also involved in synthesis of oestrone, a type of estrogen. Obesity, increased fat consumption, radiation therapy [ 94 ]. Evidence is accumulating that certain environmental pollutants contribute to estrogenic activity and may contribute to the prevalence of breast problems in the industrialized world. Alcohol consumption is linked with breast cancer risk. This association was felt to be secondary to the fact that consumption of alcohol enhances level of hormones in the blood [ 95 ].

BRCA1 and BRCA2

These are two genes that have been recognized as possessing the firm relationship with breast cancer. Both emerge to contain comparable biological activities such as DNA damage repair and, in their variant kind, they enhance the danger of breast cancer and other ovarian cancers. The preeminent knowledge accessible to date is based on a joint investigation of 22 researches, 11 which established that the prevalence of breast cancer is 65% at 70 years of age in women who acquired a BRCA1 gene and 45% in those women who are carriers of BRCA2 genes. The prevalence of breast cancer in carrier of these genes is 10–30 times more than those females that have no inherited gene variants. In spite of the big boost in breast cancer danger linked with BRCA1 and BRCA2 genes, they are responsible approximately 5% of all breast cancers, as merely 1 in 1000 females have acquired one of them. There are several tribal Subgroups in which BRCA1 and BRCA2 genes are more possible to be innate (e.g. approximately 1% of females of Ashkenazi Jewish descent have acquired increased risk BRCA1 or BRCA2 genes; analogous variants are moreover familiar in women belong to Iceland and different Scandinavian countries). Individual risk indicator as an outcome of hereditary testing for BRCA1 and BRCA2 remains a demanding experience. Almost 2000 variants have been found in the two genes (BRCA1 and BRCA2) and, for numerous; it is yet not recognized whether or not they enhance prevalence of breast cancer. One possible sign is the site of the variant in the gene; it indicates that variants in few parts of the genes might cause bigger threat of breast cancer than others [ 96 , 97 ]. Even though all females who acquire a BRCA1 or BRCA2 variant do not essentially cause breast cancer, it is uncertain what other determinants such as genetic or environmental persuade the risk of breast. There is also promising data that determinants for breast cancer might perform in a different way for carriers of BRCA1 or BRCA2 variants than for females lacking hereditary vulnerability because of these genes [ 98 ]. Literature review also recommends that high-risk genes other than BRCA1 and BRCA2 possibly enhance the risk of developing breast cancer, mainly for younger females.

Fifth most common cause of cancer death is breast cancer. The mortality and age standardized prevalence of breast cancer is higher in the United States compared to world. In Poland, seventeen percent of disease cases occur due to cancer and 14% deaths occur due to cancerous changes. Worldwide death due to breast cancer calculated in 2004 was 519,000 [ 99 ]. In the United States alone, approximately 1,208,000 cancer cases are reported per year and that some 538,000 people die from the previous manifestation of this disease condition, representing about one fifth of the total annual deaths from all causes [ 74 ].

Stages of breast cancer

According to the report of breast cancer.org Stages of the breast cancer depends upon the size and type of tumor and how much the tumor cells have been penetrated in the breast tissues [ 100 ]. Whereas stage 0 describes the non invasive and stage 4 describes the invasive kind of tumor. Descriptions of those tumor stages are:

This is the non invasive stage of tumour which indicates that both cancerous and non cancerous cells are within the boundaries of that part of the breast in which the tumor begins to grow and no evidence found of their invasion in the surrounding tissues of that part, the example of this tumour stage is ductal cell carcinoma in situ (DCIS) [ 101 ].

This stage describes as the invasive breast carcinoma and microscopic invasion is possible in this stage. It has two categories that are 1A and 1B stage. The category 1A describes the tumor which measures up to 2 cm and none of the lymph nodes are involved in it while stage 1B describes that small group of cancer cells larger than 0.2 mm founds in lymph node [ 102 ].

Stage 2 also has two categories 2A and 2B. Stage 2A describes that the tumour is found in axillary lymph nodes or in sentinel lymph nodes but no tumor found in breast. The tumor can be smaller or larger than 2 cm but not more than 5 cm. However stage 2B describes that the tumor could be larger than 5 cm but can’t reach to the axillary lymph nodes [ 103 ].

It has been divided into three sub categories that are 3A, 3B and 3C. Amongst which stage 3A describes that no tumor is found in breast but it can be found in 4–9 axillary lymph nodes or in sentinel lymph nodes while stage 3B describes that the tumour can be of any size but have caused swelling or ulcer on the skin of the breast and can have spread up to 9 axillary lymph nodes or to sentinel lymph nodes stage 3B can be considered as inflammatory breast cancer which includes red, warm and swollen skin of the breast. However stage 3C describes the spread of tumor up to 10 or more than 10 axillary lymph nodes and it also have involved the lymph nodes above and below the clavicle [ 104 ].

This is the advanced and metastatic stage of cancer and this stage describes the spread to other organs of the body that is lungs, bones, liver brain etc [ 105 ].

History and physical examination

The clinical history of patients with breast cancer is aimed at investigating cancer threat and demonstrating the occurrence or lack of manifestations indicative of breast illness [ 106 ]. It must comprise age at menarche, menopausal condition, earlier pregnancies and utilization of hormone replacement therapy after menopause or utilization of oral contraceptives. Personal history as well as family history should be carried out in detail. Personal history includes age at diagnosis of breast cancer, previous breast biopsies and treatment of other cancer with use of radiations. Family history includes history of ovarian cancers and breast cancer in first degree relatives. Patents should be examined for particular manifestations such as breast pain, weight loss, pain in bone, tiredness and nipple discharge [ 107 ]. Physical examination includes inspection of breasts, area around neck and collarbone, and armpits (axillae) carried out by clinicians [ 108 ]. Breasts are observed for any deformities such as lumps or other manifestations of breast cancer. Lymph nodes are also examined that are usually enlarged in patients with breast cancer.

Self examination

Usefulness of the breast self-examination is contentious because the advantage in conditions of reduced deaths has not been established [ 109 ]. Most physicians educate females to carry out monthly BSE to become recognizable with their usual structure and authorize them with reference to their own healthcare [ 110 ]. Women are guided for self examination of the breast cancer. Women can find abnormalities in size and shape of breast on self examination [ 111 , 112 , 113 ]. Alipour et al. [ 114 ] conducted a study to investigate the the SMS based and paper based paper learner’s satisfaction and learning effect. Gynecologists gave printed materials and text messages regarding facts of breast cancer and breast cancer tests. Doctors found higher motivation and better effects in the SMS group than the printed material group. Sreedharan et al. conducted a study in United Arab States hospitals. Self administered structured questionnaire was used to investigate practices of self examination and knowledge. Satisfactory results were found from this study [ 115 ]. Ozkan et al. [ 116 ] investigated the level of knowledge regarding self examination of the breast cancer among 113 midwifery and nursing students. These researches have shown that continuous education program about breast cancer can raise the awareness among the population. Ceber et al. [ 117 ] conducted studies on breast self examination and health beliefs of Turkish women and stated that physical illnesses and early death can be prevented by early diagnosis of breast cancer. He further stated that one out of seven patients with breast cancer is diagnosed in time. Beydag and Karaoglan [ 118 ] investigated the awareness about breast self examination in 1st and 4th years students and concluded that 4th years students have more knowledge about breast examination than the 1st years students.

Ultrasound breast imaging

There are numerous researches behind the application of adjunctive screening ultrasound in elevated hazard women with thick breast tissue, which reveals a significant but established figure of false positives [ 119 , 120 ]. There is no randomized clinical study conducted for investigation of impact of screening ultrasonography on mortality rates of breast cancer. Entire breast ultrasound might permit the Physicians to display for breast tumors not measured by long-established mammography, particularly in thick breasts wherever mammography sensitivity is lesser [ 121 ]. Ultrasound breast imaging shows the size and position of tumour whether it is filled with fluid or is solid and needs to be biopsied to rule out cancer. This examination is quickly becoming a routine procedure for diagnosing lumps in young women [ 122 , 123 ].

Nuclear medicine

It is a type of molecular imaging wherever a radioactive substance (radiopharmaceutical) is introduced to an individual and the radiation from the radiopharmaceutical is displayed by perceptive emission detectors including gamma cameras and PET detectors and gamma Cameras located exterior to the body of patient. Combination of CT and gamma camera and the combination of CT and PET is a main progress in enhancing recognition and vicinity of disease.

Single photon emission computerised tomography (SPECT)

This procedure utilizes solitary photon radionuclides including gallium-67, iodine-131 and technicium-99 m that discharge gamma rays. It is a efficient scan and is precise for organ of curiosity. It can also be employed to the entire body, is comparatively secure in expressions of radiation quantity and is fine in recognition of primary and metastatic cancers. Iodine-131 is together indicative and remedial for cancer of thyroid [ 124 ].

Positron emission tomography (PET/CT)

In expressions of radiation quantity, PET/CT is also comparatively secure and utilizes positron emitting radionuclides including oxygen-15, flouoride-18 and carbon-11. The frequently utilized tracer in positron emission tomography is a radioactive type of glucose such as [18F]fluoro-2-deoxy- d -glucose. Tissues with enhanced metabolic requirements including developing cancer cells, demonstrate increased uptake of the tracer and displays on the scan. With combination of CT and PET, significant information regarding numerous situations affecting the different organs of the body is simply mapped. PET/CT is extremely perceptive and precise for predicating occult and different areas of loco-regional lymph nodal extent and/or far-away metastases not obvious by regular imaging, therefore altering staging in up to 25% of the patients. This procedure is employed for the management planning by describing spread of primary illness. It is also employed in re-staging after management ailment relapse and treatment follow up [ 125 ].

Tumor markers

Porika et al. [ 126 ] stated that tumour markers should be measured in all stages of the breast cancer including metastasis prediction, treatment, diagnosis and screening. Thirteen verities of tumor markers of breast cancer are measured, six out of 13 are novel for the guideline. The different varieties displayed proof of clinical use and are suggested for utilization in practice [ 127 ]. It is particularly significant that the comparative autonomy of the markers in reference to other accessible markers to demonstrated so as to evade the gratuitous price and expenditure of redundancy [ 128 ]. Furthermore, it is significant that the physician be attentive of the restrictions in together specificity and sensitivity of every marker so because not to specificity and sensitivity of every marker so since not to over- or under-interpret the prognostic worth of a few investigation. With these caveats in intelligence, trial submission of tissue, germ-line and soluble tumor markers can recover medical care of individuals at threat for and with breast cancer.

It can be employed for monitoring of patients with breast cancer. High blood levels are seen in <10% of patients in the beginning of breast cancer and in approximately 70% of patients with advanced stage of breast cancer. The levels of CA 15-3 typically fall after successful management. However CA 15-3 can also be high in other types of cancers and in few non-cancerous conditions including hepatitis and benign breast conditions.

It is another marker for monitoring of patients with breast cancer. This test does not seem to be any better to identify early or advanced stage of breast cancer. This tumor marker is seen in other types of cancers and in few non-cancerous disorders.

Estrogen and progesterone receptors

For the identification of breast cancer, breast cancer tissues are investigated for estrogen and progesterone receptors including HER2 antigen. These tests give information regarding the aggressiveness of cancer and response of certain drugs used for treatment of breast cancer.

Immunohistochemistry

Immunohistochemistry (IHC) has grown to be an essential component of pathology. Although eosin and hematoxylin stain is the primary foundation for diagnostic pathology of the breast, Immunohistochemistry stains give valuable and sometimes very important information. Furthermore, taking into consideration the part of hormonal treatment in hormone receptor–positive breast tumors, as well as the accessibility of targeted chemotherapeutic drugs for HER2-positive patients, Immunohistochemistry knowledge indicates a key element of workups. Careful use of Immunohistochemistry stains in combination with E & H test assists determine mainly diagnostic matters encountered by clinicians during their routine practice. Clinicians should be well-known to utilize the each immunostain and its restrictions to evade errors in interpretation. Immunohistochemistry stains assists in differential diagnosis of challenging epithelial disorders of the breast. They should be selectively and sensibly utilized and their results must be understood with the differential diagnoses in consideration and with an understanding of potential drawback [ 129 ].

MRI and breast cancer

Mammography has been considered as an appropriate screening method for breast cancer detection for many years [ 130 ] but it can’t distinguish between the solid and cystic masses and can miss up to 10–15% of the cases however MRI provides more accurate results and clear benefit to the women who are developing breast cancer due to the BRCA1 and BRAC2 genetic mutation and are present with the axillary lymph adenopathy [ 131 ].

Breast biopsy

Breast biopsy is the simply best technique for diagnosing breast cancer [ 132 ]. There are numerous different types of breast biopsies. To enhance diagnostic precision and get rid of as many false negative results as possible, breast imaging, clinical breast examination and biopsy are performed concurrently (triple test).

Fine needle aspiration

A thin prickle is employed to get cells from the abnormal area or a breast lump [ 133 ]. Ultrasound can be used to assist direct the prickle. A restricted anesthetic might be used to anesthetize the region where the prickle will be inserted [ 134 ].

Core biopsy

A wider prickle is to get a portion of tissue (a core) from the abnormal area or breast lump [ 135 ]. It is typically made under restricted anesthetic, thus breast is insensitive, while patient may experience little hurt or uneasiness at what time the anesthetic is given [ 136 ]. MRI, ultrasound and mammogram can be used to guide the prickle for the duration of core biopsy [ 137 ].

Vacuum-assisted stereotactic core biopsy

In this core biopsy, different tiny tissue samples are taken via single tiny incision in the skin with a prickle and a suction-type device [ 138 ]. It is carried out using local anaesthetic. MRI, ultrasound or a mammogram may be employed to direct the prickle into position. The patient may experience little uneasiness during the process [ 139 ].

Surgical biopsy

If the abnormal vicinity is too minute to be biopsied by another procedure or the biopsy outcome is not apparent, a surgical biopsy is carried out. Prior to the biopsy, a guide wire may be placed into the breast to assist the medical doctor locate the abnormal tissue. Local anesthetic can be used and the physician may use MRI, ultrasound and mammogram to direct the wire into position. The biopsy is after that carried out under a general anesthetic. Little area close to breast tissue and lump are detached, alongside the wire [ 140 , 141 ].

Digital mammography

It helps to find lumps in dense tissue. The image can also be easily stored and transmitted to another radiologist for a second opinion [ 142 , 143 , 144 ]. Tarhan et al. [ 12 ] stated mammography may give false negative and false positive results in patients with dense breast tissues. Kanaga et al. [ 145 ] stated that the practice of mammography is 19% in Malaysian women as compared to other study which was 10.5%. Lack of health insurance coverage, low income and embracement were the main barriers to mammography as mentioned in earlier studies. Mammography is considered as the gold standard test for early detection of breast cancer [ 146 ] but in case of scarce resources in some areas in breast health awareness program should be promoted for the early detection of breast cancers and the staff should also gets the training of clinical breast examination so that the patient get diagnosed at earlier stage especially in those areas where mammography is unavailable [ 147 ].

PEM and MRI in breast cancer patients

Hence both the positron emission mammography and magnetic resonance imaging have proven breast cancer detection sensitivity, however hormone replacement therapy, post menopausal status and breast tissue density has no influence on the sensitivity of PEM and MRI. Positron emission mammography can be used as an alternative of MRI in patients who don’t want to have an MRI due to multiple reasons such as time issues, limited budgets, lack of interest, claustrophobia (fear of being kept in as small space) [ 148 ]. However, both have the similar sensitivity to detect cancerous lesions comprehending invasive and ductal carcinoma in SITU [ 149 ].

In the management of breast cancer, aim is to preserve quality of life with prolonged life expectancy. The use of bioflavonoids may inhibit estrogen formation [ 150 ]. Effective communication between doctors and patients plays an important role to improve clinical outcome. Oshima et al. [ 151 ] reported that effective communication between doctors and patients is effective. A study conducted in Japan indicates that this communication helps the patients to cope with adverse effects. Doctor patient communication enhances the quality of life of breast cancer patients [ 152 ]. Previous studies have shown that less exposure from radiations, higher family monthly income, long years after diagnosis, higher education, initial stage cancer and younger age were considerably related with better quality of life (QOL) in patients with breast cancer [ 153 ]. Breast cancer is less common in breast feeding women, but the protective effect of this factor is not clearly investigated [ 154 ]. Cancer is a fatal disease affecting humankind in every country. Vinblastine and vincristine was introduced in 1961 as anti cancer drugs. CIPLA has improved the process of isolating vinblastine and vincristine in the World [ 155 ], and India is exporting these alkaloids to European countries and the demand is steadily increasing. The main forms of treatment for cancer in humans are surgery, radiation and chemotherapeutic agents. The drugs can often provide temporary relief of symptoms, lengthening of life and occasionally cures the disease. Many hundreds of chemical drugs of known classes of cancer chemotherapeutic agents have been synthesized [ 156 ]. The activity of these compounds is based on their capacity for biological alkylation. The effective dose of such alkylating agents was almost the same as the toxic dose. Multi-targeted therapy could be more effective, because the recurrence rate of cancer is high and death occurs due to metastasis. Deng et al. [ 157 ] reported that Pemetrexed and Lobaplatin is prescribed in metastatic breast cancer. Huang and Cao [ 158 ] reported that cantharidin sodium injection is effective in the management of breast cancer. Cantharidinate sodium injection is herbal origin and is prepared in China for treatment of breast cancer. Breast cancer management strategies differ depending on the step of the cancer—its mass, place, whether it has extended to other organs of the body and the physical condition of the individual. Present management for breast cancer includes targeted therapies, hormonal treatment, radiation therapy and surgery.

Psychological adjustment to breast cancer

Breast cancer is extremely common and very worrying experience for numerous females every year in developing and developed countries [ 159 ]. Psychological research has given an image of the emotional and community impact of breast cancer on females’ lives, and of factors linked with better versus worse amendment. Psychosocial mediations have been helpful in reducing patients’ grief and improving their life quality. Current study also recommends that psychological aspects might be associated with potentially significant biological ailment linked processes. Additionally, to giving an idea of the psychological aspects in breast cancer, investigation in this vicinity has given a foundation for further studies on adjustment to health-related nervous tension in common [ 160 ].

This is the foremost management strategy for individuals whose breast cancer has not extended to further areas of the body and is also a choice for further complex stages of the illness [ 161 , 162 , 163 ]. The kinds of breast cancer surgery vary in the quantity of tissue that is excised with the cancer; this depends on the cancer’s characteristics, whether it has extended, and the patient’s special feelings. A few of the most familiar kinds of surgery include:

Lumpectomy (breast conserving surgery)

Some patients diagnosed with breast cancer undergo some type of surgery [ 164 ]. According to American cancer society, lumpectomy or partial mastectomy is the procedure of removing the part of the breast that contains malignant tumor along with some healthy tissues and surrounding lymph nodes leaving the major part of the breast intact as possible [ 165 ]. This practice generally experienced in women that are in their initial phase of cancer, however the patient also requires another type of treatment such as radiation therapy, chemotherapy or hormone replacement therapy along with this procedure. Most surgeons and patients prefer lumpectomy initially rather than having the complete breast removal, especially if the patient is more concerned about losing her breast [ 166 ]. However, adverse effects of lumpectomy are tenderness, temporary inflammation, sclerosis and changed appearance of breast, etc [ 167 ].

Mastectomy is done to decrease the risk of development of breast cancer [ 168 ]. Bilateral prophylactic mastectomy decreases the chances of development of breast cancer but does not eliminate the risk of developing cancer completely [ 169 ]. Aromatase and tamoxifen decreases the risk of contra-lateral breast cancer and it is considered more effective than contra lateral prophylactic mastectomy [ 170 ]. Mastectomy is considered the most effective method of dealing with an already diffused case of breast cancer, for which a lumpectomy was not decisive enough. Nevertheless, the loss of breast leads to feeling of asexuality and loss of self-image and consequent depression in most women [ 171 ].

Reconstructive surgery

Females who have a mastectomy might as well have breast renovation, either immediate reconstruction or delayed reconstruction. It is performed to get better the look of the breast following tumor surgery. All females having a mastectomy must be presented the option to converse reconstructive surgical treatment [ 172 ]. Mastectomy is a comparatively simple surgical practice that typically results in stay in hospital for 1–2 days. Deficiency of the breast mass changes the patient’s special look and can create wearing a few forms of clothing difficult. The utilization of an exterior prosthesis to tackle these problems can be awkward and scratchy, particularly for females with huge breasts. Though, the most significant issue of mastectomy is the psychosocial effect of the physical and aesthetic distortion, which can comprise nervousness, sadness, and negative impacts on body figure and on sexual activity [ 173 ]. Breast reconstruction is commonly requested by females with breast cancer who are unable for breast-conserving treatment and females with an increased hereditary danger for breast cancer. Existing breast reconstruction procedures are miscellaneous and might engage the utilization of prosthetic implant or an autologous tissue flap, or both. Despite of the method employed, cancer might relapse in the reconstructed breast; additionally, in autologous tissue flaps reconstructed breasts, little complexity such as fat necrosis may take place. Researches recommend that breast reconstruction restores body representation, proves vigor, femaleness, and sexuality; and optimistically influences the patient’s feelings of comfort and life quality [ 174 ].

Ovarian ablation as adjuvant therapy for breast cancer

Ovarian ablation has been employed as management for breast cancer [ 175 ]. There are numerous techniques of ovarian ablation such as radiation induced ablation, surgical removal of ovaries and chronic utilization of luteinizing hormone-releasing hormone (LHRH) analogs. Additionally, there are few proposals that cytotoxic chemotherapy might perform by inducing ovarian ablation in premenopausal females with breast cancer. Of the abundant case series and clinical studies of ovarian ablation conducted in the earlier period, numerous have been laden with methodologic issues. Meta-analysis of randomized clinical studies demonstrates a momentous enhancement in overall survival and disease-free survival for females whose ovarian ablation were performed as adjuvant treatment compared to those females who did not. Literature review indicates that ovarian ablation may be employed an alternative therapy for breast cancer [ 176 ].

Role of estrogen and progesterone receptors in the management of breast cancer

The estrogen receptor assay has developed into a typical practice in the treatment of complex breast cancer [ 177 ]. Tumors missing estrogen receptor react occasionally to endocrine treatment, while improvement proportions of 50–60% are seen in estrogen receptor positive tumors. Current researches demonstrate that the estrogen receptor condition of the principal cancer is a superior interpreter of the endocrine reliance of metastatic cancers at the moment of clinical deterioration. Additionally, the deficiency of estrogen receptor in the primary cancer is an significant self-regulating predictive display of higher incidence of relapse and shorter survival. Quantitative investigation of estrogen receptor and an analysis for progesterone receptor are two procedures for enhancing the precision of selecting or rejecting individuals for hormonal treatment; cancers with a elevated quantitative estrogen receptor amount or those with a positive progesterone receptor show the maximum response. Initial investigation demonstrates that the existence of progesterone receptor might be a improved indicator of tumor hormone dependence than quantitative estrogen receptor [ 178 ].

Anti-estrogen therapy

It can be used in such types of cancers that are affected by hormones and the tumor has hormone receptors such as estrogen receptors. Clarke et al. [ 179 ] stated that the most common category of drugs that are used in breast cancer is anti estrogen, which includes the agents that are (tamoxifen, raloxifene, toremifene etc). Tamoxifen inhibits the hormone oestrogen from entering into cells of the breast cancer. This mechanism inhibits the breast cancer cells from developing. Tamoxifen can be suggested to treat female of any age group. However tamoxifen is considered as the drug of choice in women that have positive estrogen receptor breast carcinoma. Tamoxifen is a selective estrogen receptor modulator (SERMS) and acts like estrogen on other parts of the body such as uterus. However, it demonstrates anti estrogen properties of breast tissues and competes with estrogen for binding to the estrogen receptors in the breast [ 180 ]. If we have to discuss about the toxic effects of anti estrogen therapy, comparatively there is very least toxicity found in it as compared to other cytotoxic drugs [ 181 ]. While some patients withdraw the treatment before completing the course of drug due to the side effects such as hot flushes, gastro intestinal problems and vaginitis etc. Though, the medical indications for discontinuing antiestrogen therapy include adeno carcinoma, sarcoma and thrombo embolic diseases etc. Any how the American society of clinical oncology recommends Tamoxifen as standard adjuvant therapy for patients with Estrogen positive breast carcinoma [ 182 ]. On the other hand Fulvestrant; Faslodex has entirely anti estrogenic action and is considered as estrogen antagonist it demonstrates anti neo plastic activities in breast tissues without having a positive effect on the uterus and bones, which may lead to certain side effects if taken for a long period of time such as osteoporosis [ 183 ]. Tamoxifen and raloxifene are selective estrogen receptor modulators (SERMs), a set of medicine that selectively prevents or motivates oestrogen-like activity in different tissues, affecting the estrogen receptors [ 184 ]. Tamoxifen exhibits its oestrogen antagonist action in numerous tissues such as uterus, liver, bone and breast [ 185 ]. It was used as adjuvant treatment in estrogen receptor positive patients and tamoxifen was accepted by the United States Food and Drug Administration (FDA) in 1998 for the impediment of breast cancer for females at elevated danger [ 186 ]. This verdict was based on the outcome of a experiment carried out by the United States National Cancer Institute that was interrupted premature as an intervening study indicated that tamoxifen decreased breast cancer prevalence by approximately one half [ 187 , 188 ]. Four big prospective studies have investigated the efficacy of tamoxifen versus placebo for breast cancer danger decline for females at elevated danger of breast cancer [ 189 ]. A summary of these studies demonstrated a 38% general decline in breast cancer occurrence for females at increased danger of breast cancer who administered tamoxifen for the period of 5 years and also indicated that tamoxifen inhibits only estrogen receptor positive breast cancers (RR ~ 50%) with no influence on estrogen receptor negative breast cancer [ 190 ]. A variety of adverse effects have been reported for females taking tamoxifen, such as venous thrombosis, cataract, endometrial cancer, menstrual disorders and hot flushes. A study indicated that the risk decreasing activity of tamoxifen expands beyond the vigorous management phase of 5 years, and remains for minimum 10 years, whereas the majority of adverse reactions do not carry on behind the 5 year management duration [ 191 ]. Raloxifene, has also been revealed to decrease danger of breast cancer, however seems to exert some adverse reactions [ 192 ]. During the precedent periods, clinical studies carried out to investigated the efficacy of raloxifen on fracture and osteoporosis, showed a 44–76% risk decline of breast cancer prevalence in the raloxifen treated patients as compared to the placebo group [ 193 ]. A randomized clinical study of Raloxifen and Tamoxifen was planned for comparing the efficacies of raloxifen and tamoxifen on postmenopausal females with an enhanced 5-year threat of breast cancer as expected by the Gail model [ 194 , 189 ]. The study demonstrated that raloxifen was comparable to the tamoxifen in decreasing the threat of invasive breast cancer and was linked with a minor danger of cataract and thromboembolism than tamoxifen. In 2007, approximately 10 years following the endorsement of tamoxifen, the FDA permitted raloxifen for the impediment of breast cancer for postmenopausal females with osteoporosis and for postmenopausal females at increased danger for breast cancer. In Australia, tamoxifen is prescribed for the treatment of breast cancer and osteoporosis.

Aromatase inhibitors

These are compound designed for decreasing oestrogen formation by targeting aromatase, the enzyme complex accountable for the last stair in the formation of estrogen [ 195 ]. The third-generation aromatase inhibitors including letrozole, exemastane and anastrozole are in present utilization [ 196 ]. Randomized clinical trial conducted for investigation of these agents in the treatment of breast cancer has indicated that these compounds contain an outstanding effectiveness in treating females with advanced disorder. Clinical study indicated that females managed with aromatase inhibitors had a superior contra lateral breast cancer threat decline than females managed with tamoxifen [ 131 ].

Radiation therapy

It is useful for reducing the necessity of mastectomies. A combination of a lumpectomy and radiation therapy is being increasingly used over a mastectomy in the early stages of breast cancer [ 197 ]. A study was conducted in India. For this study 135 women were selected, most of them had undergone mastectomy. At the time of analysis, there was no local recurrence after hypo fractioned radiation therapy and metastatic disease developed in only four patients [ 198 ]. Zhou et al. [ 199 ] reported that radiation therapy is effective in early breast cancer patients. This study was conducted on 143 women who underwent either routine or intra operative radiation therapy after breast conserving surgery. At 54 months of follow up, there was a significant local control of the tumour. High-energy rays from radiation therapy kill cancer cells. This therapy affects only the cells that are treated. Use of radiation therapy may be done after breast cancer surgery to destroy the remaining cells in the chest area.

Brachytherapy

It is a kind of radiotherapy [ 200 ]. It might be recognized as accelerated partial breast irradiation. It directs radiation merely to the area around the vicinity wherever the cancer was. This might replace the requirement to provide radiation to the whole breast. It also decreases the number of management sessions [ 201 ].

• Chemotherapy

The process of killing cancer cells by using certain medicines is termed as chemotherapy [ 202 , 203 ]. It can be given in both situations, before and after surgery, depending upon the condition of the patient. According to the American cancer society the medicines include in chemotherapy are Docetaxel, Paclitaxel, Platinum agents (cisplatin, carboplatin), Vinorelbine (Navelbine), Capecitabine (Xeloda), Liposomal doxorubicin (Doxil), Cyclophosphamide (Cytoxan), Carboplatin (Paraplatin) etc [ 204 ]. However it has various side effects [ 205 ]. Metastatic or secondary breast can is difficult to treat but it can be controlled and sometime for various years [ 206 ]. Chemotherapy can be prescribed to manage metastatic breast cancer to minimize or sluggish its development. It can also be administered to decrease some manifestations. Other treatment option can be initiated prior or alongside chemotherapy.

Taxol is used clinically in the treatment of ovarian cancers and is undergoing clinical trials against metastatic breast cancers [ 207 ]. It may also have potential value for lung, head and neck cancers. Taxotere is a side chain analogue of taxol, which has also been produced by semi synthesis from 10-deacetyl-baccatin III [ 208 ]. It has improved water solubility, and is being clinically tested against ovarian, and breast cancers. It can be used in those where resistance to cisplatin has been observed [ 209 ].

Anthracyclines

Anthracycline are commonly prescribed in the treatment of breast cancer [ 210 ]. They impede with enzymes associated the DNA copying, which is desired for cells to separate to create new cells. Epirubicin and doxorubicin are the most commonly used medicines in breast cancers. There is proof that anthracyclines functions better than various other chemotherapy medicines [ 211 ]. However these have adverse reactions such as damage to the heart and loss of hair [ 212 , 213 ]. Prior to start of medicines, patient should converse with clinician any probable adverse reactions of drugs used and how these medicines might influence life quality.

Thermochemotherapy

Medifocus heat management in combination with chemotherapy enhanced the shrinkage of median cancer in the thermochemotherapy arm to 88.4%, whereas for chemotherapy alone the shrinkage of median cancer was 58.8%. For the thermo-chemotherapy management arm, approximately 80% of breast cancers had a cancer size decrease of 80% or more, compared to merely 20% for the chemotherapy alone [ 214 ].

Complementary therapies

Women with breast cancer occasionally desire to use complementary therapies along with their medical therapy [ 215 ]. These therapies are usually not investigated in randomized clinical trials [ 216 ]. Some female believe that they have benefited from a number of these treatments [ 217 ]. Vitamins, nutritional supplements, yoga, meditation, visualization, traditional medicines and acupuncture are included in complementary therapies.

Medicinal plants

Screening of plant extracts for anticancer activity started in 1961 by National cancer institute in the USA, and up to 1981 (20 years) about 1,14,045 plants had been screened of which only 3.4% (representing about 3400 different species) have been observed to be active in one or more biological systems.

Ganoderma lucidum (Polyporaceae)

It contains ganoderic acid, ganoderic acid G, ergosta, ergosterol peroxide ganoderic acid G, ergosta, ergosterol peroxide, methyl ganoderate A, B, ganoderic acid C2. It is an anticancer [ 218 ]. Jiang et al. [ 219 ] reported that the Ganoderma lucidum suppresses growth of breast cancer cells through the inhibition of Akt/NF-kappa B signaling. It is used to treat cancer cells. It inhibits the transcription factor NF-kappa B and inhibits the invasive behavior of breast cancer cells. The exact mechanism for inhibition of cancer cells is not understood. The study showed that the proliferation of breast cancer MDA-MB-231 cells is inhibited and Akt/NF-kappa B signaling is suppressed. Phosphorylation of Akt at Ser473 is suppressed by this plant and expression of Akt is suppressed, as a result NF-kappa B activity in MDA-MB-231 cells is inhibited.

Momordica charantia (Cucurbitaceae)

The parts used are fruits, leaves and seeds. It contains glucoside, albuminoids, fatty acids, non polar lipid, linolinic acid, palmitic acid, myrtenol, hexenol, benzyl alcohol, acylglycosylsterols and glycoproteins [ 220 ]. It is hepatoprotective, tonic, stimulant, emetic, laxative, stomachic and cancer [ 221 ]. It is used to treat gout and rheumatism. Ray et al. [ 222 ] reported that Momordica charantia extract inhibits breast cancer by modulating cell cycle regulatory genes. This study was conducted in vitro models. An extract of this plant was investigated in human breast cancer cells, MCF-7 and MDA-MB-231, and primary human mammary epithelial cells. This extract was able to decrease cell proliferation and apoptotic cell death was induced. Survivin and claspin expression was inhibited by this extract.

Carthamus tinctorius (Asteraceae)

The parts used are flowers and seeds. It contains palmitic acid, hexadecanolenin, coumaric acid, daucosterol, apigenin, kaempferol, trans-3-tridecene-5, 7, 9, 11-tetrayne-1, 2-diol, trans-trans-3, 11-tridecadiene -5, 7, 9-triyne -1, 2-diol [ 223 ]. It is used in colds, flu, fevers, hysteria, anemia, and diabetes mellitus. It is an antioxidant [ 224 ] and alpha glucosidase inhibitor [ 225 ]. Loo et al. [ 226 ] reported the efficacy of this plant in breast cancer. MDA-MB-231 breast cancer cell and normal human mammary gland cell were treated with a compound that contains Carthamus tinctorius. This compound observed inhibition of cell proliferation. Inhibition of cell proliferation was dose dependent. Its cytotoxic activity was more than commonly used cytotoxic drugs.

Viscum album (Viscaceae)

Part used are leaves and stem. It contains sinapylflavanone, glucopyranoside, flavanone, hydroxy flavanone and viscin [ 227 ]. It is antioxidant, cardiac tonic, and anti-cancer [ 228 ]. It is used in palpitation, vascular spasms, asthma, dizziness, vertigo and headaches. Gunver et al. [ 229 ] reported the efficacy of this plant in breast cancer.

Calendula officinalis (Asteraceae)

The parts used are leaves. It contains triterpene, calendula glycoside, butyl ester, flavonol glycosides, and carotenoids [ 230 ]. It is anti-inflammatory and anti-cancer [ 231 ]. It is used in carcinoma of the vagina, and cervix. Pommier et al. [ 232 ] reported the efficacy of Calendula officinalis for the prevention of acute dermatitis during irradiation for breast cancer.

Citrullus colocynthis (Cucurbitaceae)

The parts used are seeds and fruit. It contains phytosterol, flavones C-glycosides, saponins, aspartic acid, arginine, colocynthin, colocynthitin and cucurbitacin glycosides [ 233 ]. It is used in constipation and carcinoma of the breast [ 234 ]. It is an emmenagogue, ecbolic, cathartic, hydragogue and antioxidant [ 235 ]. This plant has growth inhibitory activity. Cucurbitacin glucosides have been isolated from this plant. These glycosides prevent human breast cancer cells [ 234 ].

Indole-3-Carbinol (13C)

A compound known as indole-3-carbinol, which is a plant chemical derived from cruciferous vegetables such as Brussels sprouts and cabbage, changes the way estrogen is metabolized. This compound predictably alters the endogenous estrogen metabolism towards increased catechol estrogen production and may thereby provide a novel dietary means for decreasing risk of breast cancer [ 236 ].

Silibinin and Chrysin

Previous research indicates that chrysin and silibinin function synergistically and possess significant anti-cancer activities against T47D breast cells [ 187 , 188 ]. It shows potential that the synergistic efficacy is based, at least in part, by down-regulation of hTERT and cyclin D1. Their potential activities in the established synergism among Chrysin and Silibinin should be verified by additional in vitro or in vivo researches. Study demonstrates that Chrysin and Silibinin combined might come out as an eye-catching approach based on herbal medicine for the management of breast cancer [ 237 ].

Lactobacillus acidophilus

Breast cancer and hyperestrogenism may be decreased by the inclusion of lactobacillus acidophilus in the diet. This useful bacterium helps to metabolize estrogen properly in the bowel. Clinicians can prescribe lactobacillus acidophilus that is available in different forms, including capsules in patients with breast cancer [ 238 ].

Women with breast cancer have been shown to possess selenium levels that are lower than those of women without cancer. Selenium is a trace mineral that is often lacking in refined food diets. A contrary association exists among the prevalence of human breast cancer and concentration of dietary selenium. The adding of Selenium to the food has been revealed to reduce the occurrence of breast cancer [ 239 ].

Targeted therapies

These are drugs prescribed to manage some types of breast cancer. The mainly familiar targeted treatment is the drug Herceptin [ 240 ]. It is prescribed to manage HER2 positive breast cancer. It functions by preventing the cancer cells from developing and progressing [ 241 ].

Gene therapy for carcinoma of the breast

Gene therapy is a remedial strategy that is considered to correct particular molecular deformities associated with the progression or development of breast cancer [ 242 ]. Mutated BRCA1 and p53 genes recognized as cancer susceptibility gene are involved in progression of cancer [ 243 ]. Since mutational inactivation of gene activity is reserved to cancer cells in these contexts, cancer gene modification techniques may give an opening for selective targeting without major hazards of normal, non-cancer cells [ 244 , 245 ]. Both BRCA1 and p53 emerge to restrain tumor cells that lack mutations in these genes, indicating that the so-called gene modification techniques may contain broader efficacy than previously considered. Raising awareness of cancer genetics has recognized these and new genes as possible targets for gene substitute treatment [ 246 ]. Early patient study of BRCA1 and p53 gene therapy have given a number of indications of possible effectiveness, but have also recognized areas of clinical trials that are wanted prior to these therapeutic strategies may be broadly employed in patients with breast cancer [ 247 ].

Oncogenes inactivation

Numerous oncogenic proteins have been recognized and linked with a variety of cancers [ 248 ]. The frequently practical strategy in clinical studies is the employment of antisense options. Oncogenes transcription also can be prevented by means of adenoviral gene E1A, which hinder erbB-2 transcription, an option helpful in managing cancer that over express this oncogenic protein [ 249 ].

Augmentation of cancer suppressor genes

The mutations in tumor suppressor genes are linked with the development of numerous cancers. Some clinical studies are being conducted to deliver p53 via adenoviral vectors to different cancers. Likewise, viral vectors have been used to administer a breast cancer gene BRCA1 and retinoblastoma gene into ovarian cancer and bladder, correspondingly. In various circumstances, this strategy will fall short, as the mutant gene indicates dominant negative activity of the normal gene. To avoid this difficulty for p53 gene therapy, a genetic repair approach rather than a gene augmentation strategy might be more successful [ 250 ].

Cancer stem-cell therapy for breast cancer

Current investigation in biology of breast has provided the foundation for the cancer stem-cell hypothesis [ 251 ]. Two significant aspects of this theory are that cancer arises in progenitor cells or mammary stem cells as an outcome of dysregulation of the normally strongly regulated method of self-renewal. As a consequence, cancers posses and are obtained by a cellular subcomponent that keeps central stem-cell functions such as self-renewal, which directs differentiation and tumorigenesis that is responsible for cellular heterogeneity. Development in the stem-cell field have guided to the recognition of stem cells in normal and malignant tissue of the breast. The investigations of these stem cells have assisted to clarify the source of the molecular complexity of breast cancer in human. The cancer stem-cell theory has significant role for timely recognition, prevention, and management of human breast cancer. Dysregulation of stem cell renewal pathways are involved in the development of both sporadic and hereditary breast cancers. These abnormal stem cells may give targets for the improvement of cancer prevention options. In addition, since breast cancer stem cells may be extremely challenging to chemotherapy and radiation, the progress of additional efficient treatments for breast cancer may need the efficient targeting of this cell population [ 252 ].

Anti-oestrogens and prevention of breast cancer

With the accomplishment of anti-oestrogens in breast tumor management, numerous studies evaluated their use as an mediator to avert breast cancer in female at high risk [ 253 , 254 ]. Tamoxifen is the antiestrogen medicine employed most commonly in the treatment of breast cancer. Administration of tamoxifen as an adjuvant treatment following surgery, normally for 5 years, decreases the risk of hormone receptor breast cancer recurrence.

Metastatic breast cancer is also managed by tamoxifen. In numerous females, tamoxifen induce the manifestations of menopause such as mood swings, vaginal discharge and hot flushes. Toremifene is one more medicine strongly related to tamoxifen. It is used an alternate drug in postmenopausal female for the treatment of metastatic breast cancer. Fulvestrant is another drug that decreases the estrogen receptor numbers. It is usually useful in postmenopausal female, even in tamoxifen resistant breast cancer. In previous studies, tamoxifen was evaluated for its efficacy in 13, 388 females at higher risk of breast cancer for the period of 5 years. The study indicated a 49% decrease in risk of increasing invasive breast cancer and as well decreased risk of opposing side breast cancer, reappearance and extended existence in the female who had tamoxifen as accessory after operation [ 187 , 188 ]. Antioestrogens are currently suggested as chemoprevention for female with atypical hyperplasia, genetic tendency to develop cancer and important family history of breast tumor. They are also prescribed because component of practice post-operative concomitant management of those with estrogen receptor positive cancers for duration of 5 years following surgery [ 255 ].

Human monoclonal antibody

Monoclonal antibodies are prepared in the laboratory [ 256 ]. These are used alone or in combination with radiation therapy and chemotherapy to locate and target cancer cells. Usually, the body’s immune system attack to foreign antigens such as infectious agents. It will then create antibodies to assist fight it off. The body does not identify cancer cells as a kind of foreign attacker. So, antibodies are then not formed. A randomized clinical trial was conducted to investigate efficacy of denosumab, a completely human monoclonal antibody against receptor activator of nuclear factor κ B (RANK) ligand, in comparison with zoledronic acid in the prevention of skeletal-related events in breast cancers individuals with bone metastases. Denosumab was found better as compared to zoledronic acid in preventing or delaying the SREs in breast cancer patients with bone metastasis. It is demonstrated that denosumab is possible therapeutic alternative for individual with bone metastases [ 257 ].

Immunotherapy

It utilizes the immune system of the body to fight against the cancer cells [ 258 ]. Cancer vaccine is one of its examples. Parts of cancer cells or cancer cells are utilized for formation of vaccines. These cells excite the body’s immune system to assist assault and destroy cancer cells [ 259 ]. Immunotherapy has turn into a significant constituent in the management of breast cancer. HER2 targeted treatment are at the present an important part of HER2 over expressing breast tumor therapy. Trastuzumab, with the new current accompaniments of pertuzumab and TDM1, encompass considerably superior breast cancer prediction. With various Federal Drug and Administration recommended antibody treatments used in together the adjuvant and metastatic settings, development progresses to be done in the area of immunotherapies. Current achievements in targeted therapies, vigorous particular immunotherapy, grasp assure for continuous success in general endurance within the adjuvant setting. The extremely precise and targeted strategy of vaccine therapy not simply avoids the adverse effects of recent standard of care therapies, active and passive immunotherapies including ipilimumab; however presents remedial strategy beyond now the HER2-overexpressing individuals. Even though vaccines for breast cancers have been mainly ineffective in precedent clinical studies, the most of these studies conducted in the location of late-stage metastatic illness, adverse surroundings for agents intended to stop, as different to manage, disease. With present clinical studies conducted on the adjuvant settings, immunogenicity is at the present indicating association with medical response.

Anti–angiogenesis drugs

Angiogenesis and inflammation are host-dependent manifestations of tumors that can be targeted with impediment strategies long prior to cancer start and develop [ 260 ]. Numerous prescription and non-prescription medicines are now accessible for utilization in angioprevention. Angioprevention can be proposed at four levels; first for the healthy people, 2nd for population at enhanced risk of tumor, 3rd for preneoplastic disease and 4th for prevention of cancer relapse. There are numerous achievements in prevention of cancer that reveal medical possibility and levels of interference, from no to slight to strong clinician participation. To evade toxicity whereas maintaining effectiveness, angioprevention desires to attain a level of angiogenesis prevention that is not extremely oppressive, such that hale and hearty vascular activity is maintained. These drugs block angiogenesis. In the absence of blood supply to cancer cells, they cannot develop and die. Various drugs are under investigation for the management of metastatic breast cancer. In initial stage of breast cancer, they are also investigate in the neoadjuvant (before surgery) setting [ 261 ]. Antiangiogenic treatment in breast cancer presents important promise, and numerous continuing investigations are trying to better describe the best management settings and mediator assortment. For patients with estrogen receptor positive aliment, researches recommend a relationship among resistance of endocrine and cancer dependence on angiogenic networks, suggesting a possible curative advantage in mixing endocrine treatment with antiVEGF mediator. Findings from randomized clinical studies emphasize the multiplicity in reaction to antiVEGF treatment and recommend the requirement for better choice of patient subsets further to be expected to advantage from these therapies. The recognition of biomarkers for therapy response is solitary part of deep attention, though mainly study to date has become unsuccessful to discover a relationship linking cancer-associated markers including cancer mutations and EGF expression and scientific response.

Surveillance and follow up

A regular assessment of the important in print literature conducted by de Bock et al. [ 262 ], revealed that 40% of recurring cancers are identified in asymptomatic individuals during routine visits. This information intensifies the significance of surveillance and follow-up. Clinical investigation such as history and physical examination is suggested each 4–6 months for 5 years, after that each year with annual mammography. Female on tamoxifen should go through a yearly gynecologic evaluation if the uterus exists. Female who suffers from ovarian failure secondary to management or on an aromatase inhibitor should have checking of bone fitness with a bone mineral thickness determination at the start and sometimes subsequently. Women should also be advised to adopt variable risk factors, including lessening alcohol use, reducing BMI and enhancing physical activity.

The increase of information on the pathophysiologic mechanisms of breast cancer has brought extensive development in the figure of biomolecular markers. In addition, the development of targeted drug design has grown quickly and more complicated, providing numerous agents that target these markers for in vivo investigation in animal models as well as clinical studies. The enthusiasm among scientists and Physicians about the growing management strategies is tempered by apprehension that resources are insufficient to carry the mainstream of these agents to advanced clinical trials. The challenges, then, are to choose the most capable agents to be investigated and the proper clinical studies for such evaluations. We have adopted a justifying strategy to unfolding the most extensively documented molecular targets in breast cancer. Drugs that amend the NRF have not been evaluated comprehensively so far, and such studies can boost the chances for true ‘endocrine’ strategies for management of breast cancer. Furthermore, agents that amend angiogenesis and apoptosis demonstrate an thrilling area of research, mostly in vigilantly chosen combination regimens.

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Akram, M., Iqbal, M., Daniyal, M. et al. Awareness and current knowledge of breast cancer. Biol Res 50 , 33 (2017). https://doi.org/10.1186/s40659-017-0140-9

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• PMCID: PMC6154372
• DOI: 10.1007/s13193-017-0703-9

Breast cancer (BC) has become the most common cancer in urban women. Unfortunately, most women are not aware of BC symptoms/signs, prevention, and management. In resource-limited countries like India where we do not have structured screening/awareness programs, a majority of women present with locally advanced BC. The aim of our study is to identify the present status of awareness about BC prevention, early detection, symptoms, and management in urban and rural Indian women (medical, paramedical, and nonmedical) and to assess whether education and socioeconomic strata have any role in better awareness about BC or not. We did a prospective cross-sectional observation study among the medical, paramedical, and nonmedical women in the northern part of India. We designed a questionnaire keeping in mind the three domains about BC-knowledge (questions 1-25 include risk factors, genetics, lifestyle changes, hormones, associated cancers, and modes of presentation like lump, nipple/skin changes), breast self-examination (questions 25-37), and attitude to prevention and early detection (questions 38-44). We also asked how many do breast self-examination (BSE) and what they think are the three main factors responsible for late presentation and the three main ways to increase BC awareness. The Likert scale was used for objective assessment. We analyzed the whole data using SPSS software version 15. A total of 220 women out of 270 completed the questionnaire. Out of 220 women, 26.4% were medical, 20.9% paramedical, and 52.7% nonmedical. Most women were educated (82.7%) and married (65%). 59.5% women resided in urban areas and the rest (40.5%) were from rural areas. We found that there was relatively more knowledge in the medical group; however, the skills of BSE and attitude to prevention and early detection in all the three subgroups and among rural and urban women were suboptimal and not different significantly. The three main factors responsible for delayed presentation were shyness and not knowing BSE, ignorance about BC symptoms, and social stigma of cancer along with financial constraints. The three main ways to improve BC awareness suggested were to have more advertisements on television and social media, roadside campaigns and in colleges along with group discussions and debates, and at grassroots level to involve Anganwadi workers and nurses to create more awareness in villages. There was less breast cancer knowledge and awareness among the nonmedical women compared to those among the medical and paramedical, the skills of BSE and attitude to prevention and early detection were suboptimal in all the three groups. Rural or urban dwellings did not make much difference in BC knowledge, skills of BSE, and attitude to prevention. More awareness regarding breast cancer symptoms with early detection and BSE need to be addressed with more information dissemination via social media, campaigns, and involvement of paramedics and social workers.

Keywords: Breast cancer awareness; Breast self examination.

• Research article
• Open access
• Published: 18 May 2020

Knowledge of symptoms and risk factors of breast cancer among women: a community based study in a low socio-economic area of Mumbai, India

• Ranjan Kumar Prusty 1 ,
• Shahina Begum 1 ,
• Anushree Patil 2 ,
• D. D. Naik 1 ,
• Sharmila Pimple 3 &
• Gauravi Mishra 3  

BMC Women's Health volume  20 , Article number:  106 ( 2020 ) Cite this article

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Breast cancer (BC) is leading cancer among women in India accounting for 27% of all cancers among women. Factors that make the policymakers and public health system worried are rising incidence of breast cancer in India and more importantly high death rates among breast cancer patients. One of the leading causes of high breast cancer deaths is lack of awareness and screening leading to the late presentation at an advanced stage. Therefore, the current research aimed to understand the knowledge of breast cancer symptoms and risk factors among women in a low socio-economic area of Mumbai.

A cross-sectional study was conducted at Prabhadevi, Mumbai and primary data was collected from 480 women aged 18–55 years. Structured questionnaire was used to collect quantitative data pertaining to awareness, signs and symptoms of breast cancer. Bivariate and multivariate regression techniques were used for understanding of the socio-demographic differentials in breast cancer awareness among women.

The study found that around half (49%) of the women were aware of breast cancer. The women who were aware of breast cancer considered lump in breast (75%), change in shape and size of breast (57%), lump under armpit (56%), pain in one breast (56%) as the important and common symptoms. Less than one-fifth of the women who were aware of breast cancer reported early menstruation (5.6%), late menopause (10%), hormone therapy (13%), late pregnancy (15%) and obesity (19%) as the risk factors for breast cancer. The multivariate regression analysis showed women who had more than 10 years of schooling (Adjusted Odds Ratio: 3.93, CI: 2.57–6.02, P  < 0.01) were about 4 times more likely to be aware of breast cancer than women who had less than 10 years of schooling.

In conclusion, knowledge of danger signs and risk factors of breast cancer were low among women in the community. This may lead to late detection of breast cancer among women in the community. Therefore, the study calls for advocacy and larger intervention to enhance knowledge of breast cancer among women in the particular region with a special reference to women with low education.

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Cancer incidence and mortality are growing at a vigorous pace across the globe and this transition is most striking among emerging economies. Globally, one-fourth (25%) i.e. 2.1 million cases of all female cancer diagnosed in 2018 were of breast cancer [ 1 ]. It is most commonly diagnosed cancer among females in more than 150 countries. Out of these 150 countries, breast cancer is the leading cause of mortality among all female cancers in 100 countries. The recent GLOBOCAN 2018 report shows age-standardised breast cancer incidence rate per 100 thousand females was very high in Australia (94.2), Western Europe (92.6) and Northern Europe (90.1) whereas it was lowest in South–Central Asia (25.9) region. However, the mortality rate in South Asian countries is more or less similar with greater mortality rate among most developing countries [ 1 ].

In India, the age-adjusted incidence rate of breast cancer was 25.8 per 100,000 women making it leading cancer among Indian females in 2012 [ 2 ]. Although the incidence rate was lower than many developed countries, it’s rapidly rising in Indian cities and the mortality rates were more than the United Kingdom (UK) (12.7 in UK vs 17.1 in India per 100 thousand women) which had a high incidence rate of 95 per 100 thousand females. According to National Cancer Registry Programme and GLOBOCAN 2018, there were 1,62,468 new cases of breast cancer and 87,090 deaths were reported for breast cancer in India [ 3 ]. In addition, there is a huge spatial variation across the nation with highest rates found in North-Eastern Indian states and major metropolitan cities like Mumbai, New Delhi, Kolkata and Chennai [ 4 ]. Detection of malignancy at advanced stages mainly leads to high death rates in India [ 5 , 6 , 7 ]. Lack of knowledge of signs and symptoms is considered as one of the major reasons contributing to the late detection backed by cumbersome referral pathways for diagnosis, lack of proper regional centres for treatment, incomplete treatment due to high out of pocket expenditures and several socio-economic, geographical, and cultural barriers associated with women’s health [ 5 , 6 , 8 , 9 ]. The high death among women suffering from breast cancer is a concern for the national policymakers in addition to the increasing incidence rate.

There are multiple demographic, social and biomedical risk factors of breast cancer. Age of the women, early age at menarche, delayed first birth and menopause, nulliparity, short duration lactation, use of birth control pills, obesity, excess consumption of fats, hormone replacements and more importantly women having family history are considered as significant risk factors of breast cancer by various epidemiological and clinical studies [ 10 , 11 , 12 ]. One of the meta-analysis by Vishwakarma et al. [ 10 ] carried on 24 observational studies stated that highest odds ratio (OR) obtained for risk of breast cancer was among those who never had breastfeeding (pooled OR 3.69, 95% Confidence Interval = 1.70–8.01), never married women (pooled OR = 2.29, 95% CI = 1.65–3.17), and nulliparous women (pooled OR = 1.58, 95% CI = 1.21–2.06) [ 10 ]. One of the studies in South India found higher risk of breast cancer in urban area than rural areas [ 11 ]. This study also reported that the odds of breast cancer among urban women which increased with increase in proportion of overweight or obese (BMI-body mass Index > 25), size of the waist (> 85 cm) and size of hip (> 100 cm) among both pre-menopausal and post-menopausal women. Another study in rural Maharashtra found that most of the breast cancer cases were confined to women aged 40–49 years, home makers and upper economic strata group. Further, this study found breast cancer risk was 8 times higher among unmarried women, 3 times more among nulliparous women, 2 times more likely among post-menopausal women, 10 times more among those who had never breastfed, 1.5 times higher among women who were exposed to hormonal contraceptives and 4.5 time more likely among women with history of ovarian diseases than in comparison to married, non-nulliparous, premenopausal, women who ever breastfed, who have not been exposed to hormonal contraceptives, and women without any ovarian diseases respectively [ 12 ]. There are also studies which found difference in exposure to different type of environmental pollutants as a risk factor to breast cancer [ 13 ].

Several studies focused on different preventive and curative interventions which were carried both internationally and in India [ 14 , 15 , 16 , 17 , 18 , 19 ]. Although breast cancer prevention remains a baffling task due to involvement of multiple cell types at multiple stages, most intervention literature on breast cancer suggested that modifiable risk factors may be prevented through promotion of healthy diet, regular physical activities, regulating alcohol consumption and controlling weight which is likely to reduce the incidence of breast cancer in longer time period [ 20 ]. Further, literature also suggest that delay in detection leads to poor survival and early detection leads to better and economic treatment [ 21 , 22 , 23 ]. The delays were most among the older women and were mainly due to poor knowledge of symptoms and erroneous belief related to breast cancer and it’s treatment [ 22 ]. Therefore, the present paper tries to understand the knowledge of signs, symptoms and risk factors of breast cancer among women in the study area of Mumbai.

The study was concentrated to lower socio-economic area catered by Prabhadevi maternity home and health post which comes under Municipal Corporation of Greater Mumbai (MCGM). Mumbai has a mixed health care system, inclusive of services provided by local bodies, the government of Maharashtra and public trusts and private service providers. The MCGM runs a network of primary, secondary and tertiary level facilities through medical college and hospitals, municipal general hospitals and speciality hospitals, maternity homes, dispensaries and health posts. The primary healthcare services are provided by health posts and dispensaries whereas maternity home provides specialized delivery care. The health posts were established to provide primary health services mainly in slum areas. The Prabhadevi maternity home and health post provides both primary healthcare services and maternal health care to lower socio-economic population in the Prabhadevi area of Mumbai.

The data used for the current study came from primary data collected for baseline survey of a breast cancer intervention study. The tertiary cancer specialized hospitals bear most of the burden of screening and treatment of breast cancer in India. The primary healthcare facilities in India is not well equipped with required human resources and training for cancer screening leading to late detection of cancer. So, this intervention was to test screening of breast cancer at primary care level for early detection of breast cancer cases with the available resources at present. The Prabhadevi facility was chosen for this study because it is both women centric and provides primary health care services. The cross-sectional baseline survey was conducted during November 2018 to March 2019.

The details of inclusion and exclusion criteria, sample size, sampling procedure, data collection and analysis are given below:

Inclusion criteria

Women between 18 and 55 years of age were included in the study.

Exclusion criteria

Women who were already diagnosed with breast cancer and under treatment, pregnant women and lactating women were excluded from the study.

Sample size

About 80% of women aged 30–50 years were aware of breast cancer in Vikhroli, Mumbai [ 17 ]. However, our study focused on women 18–55 years of women. One of the study in similar settings at Delhi found around half (53%) of the women (aged 14–75 years) were aware of breast cancer [ 15 ]. Thereby considering 53% prevalence, 5% level of significance and 20% non-response rate, the required sample size was calculated as 478. Information was collected from 480 women participants.

Sampling procedure

The complete area under Prabhadevi maternity home and health post was identified through the map available with Municipal Corporation of Greater Mumbai (MCGM). This health post is located at G-South ward of Mumbai. With the help of MCGM record, the low-income group housings based on criteria set by Maharashtra Housing and Area Development Authority (MHADA) were identified. Around 76 thousand low income group community population (according to MHADA, Government of Maharashtra) is catered by Prabhadevi Maternity Home under Municipal Corporation of Greater Mumbai. The whole area with around 19 thousand households was divided into 16 sections of around 1000–1400 households based on areas covered by 16 Community Health Volunteers at the health post. Mapping and house listing of the selected area/community was done to prepare a list of households having eligible women. Systematic random sampling was used to select the 480 eligible women from the list . Kish grid method was used to select women in case more than one woman was found eligible in the selected household [ 24 ].

Data collection tools (baseline)

The tools were divided into two sections a) socio-economic background of the participants b) knowledge about breast cancer with questions related to awareness and practices (See supplementary file ). The socio-economic background section focused on collecting individual level information like age, education, religion, caste, marital status of the participants. The second section was used to assess the women’s knowledge regarding breast cancer, sign and symptoms, risk factors, Breast Self-Examination (BSE), and Clinical Breast Examination (CBE) using a structured questionnaire. Women participants were asked whether they had ever heard of breast cancer. Those who have heard of breast cancers were further asked about knowledge of breast cancer signs and symptoms, risk factors and current practices using closed response questions. The questionnaire was prepared using existing literature and in consultation with the study team as well as experts constituting of oncologists, gynaecologist, public health, and social scientist. The tools were translated to both Hindi and Marathi languages for the convenience of participants. These questions were pilot tested with 20 participants (10 Hindi and 10 Marathi questionnaires each) at a similar socio-economic setting of Mumbai. The results from this pilot testing were used for modification of the words for easy comprehension of the participants. The content validity was ensured through expert consultation and pilot testing of the questionnaire. The field investigators were trained for 1 day and made familiar with the questions and ways of asking the questions. The data was collected through face to face interview with participants. Regular back-checks were conducted at the office to ensure data quality. The response rate was 96% for this baseline study.

Statistical analysis

Univariate and bivariate analysis were performed using percentage and median to know the profile of study participants, proportion of women who were aware of symptoms, risk factors and screening methods and socio-economic differential in those symptoms and risk factors. Multivariate logistic regression was used to know the socio-demographic predictors of breast cancer awareness among women in the study area. The data were analysed using IBM SPSS 26.0 packages.

Dependent variables

Women were asked ‘Have you ever heard of breast cancer?’. The response ‘Yes’ is coded as 1 and response “No” was coded as 0. This is used as a proxy variable for breast cancer awareness. Bivariate and multivariate binary logistic regression analysis was performed to see the differential and predictors of awareness of breast cancer. The other dependent variables used were specific symptoms, signs and risk factors of breast cancer to see differential socio-economic characteristics.

Independent variables

Different socio-economic variables like age, religion, caste, working status, marital status, and years of schooling of women were used as independent variables in this study.

Ethical permission

The Indian Council of Medical Research-National Institute for Research in Reproductive Health (ICMR-NIRRH) Ethics Committee for clinical studies, Mumbai has approved this study in compliance with the Helsinki declaration. Written consent from the participants was obtained during data collection. The confidentiality of the data was maintained during all the stages of research- data collection, data cleaning, and dissemination of research results.

Profile of the study participants

The median age of the participants was 39 years and 98% of the women ever attended school. The median year of schooling was 12 years. The religious composition showed 93% of women were Hindu, 3 % of women were Buddhist/Neo-Buddhist and the remaining 4 % were from Christian, Jain, Muslim religions. More than two-thirds of the women (69%) were from upper caste or no caste groups whereas one-fourth of them were Other Backward Classes (OBC) and around 6% of the women were Scheduled Caste or Scheduled Tribe (SCs/STs). Only 16% of the women were employed. Majority of women (84%) were married and 77% of them had at least one child.

Breast cancer awareness

About half (49%) of these women were ever heard of breast cancer. Breast cancer awareness was poor among women educated upto high school (10th) or not educated with only one-third of (34%) them ever heard of it. Nearly two-thirds of the women (61%) educated above 10th standard (higher education) were aware of breast cancer. Breast cancer awareness was better among middle aged women (25–34 years) than in comparison to younger (18–24 years) and older women (Table  1 ). Majority of these women had heard about breast cancer through television (53%) or from a doctor (25%) (Fig.  1 ).

Different sources of knowledge of breast cancer among women (%) who were aware of it (N = 234)

Multivariate analysis

The binary logistic regression analysis showed that education was the only significant predictor of breast cancer awareness (Table 1 ). The education of women was significantly and positively associated with awareness of breast cancer. The women who had more than 10 years of schooling (AOR: 3.93, CI: 2.57–6.02, P  < 0.01) were about 4 times more likely aware of breast cancer than in comparison to women who had less than 10 years of schooling or no education.

Knowledge of different signs and symptoms

The knowledge of different symptoms among women ever heard of breast cancer ( N  = 234) is depicted in Fig.  2 . Lump in breast was considered as a symptom of breast cancer by three-fourths of women. Interestingly, less than half of the women said abnormal discharge or blood from nipple (48%), change in shape or size of nipple (48%) and change in skin colour (47%) as symptoms of breast cancer. Only two out of five women (40%) thought breast cancer can be hereditary (not shown in figure).

Percentage of women who had knowledge of different signs or symptoms of breast cancer

The Table  2 shows the socio-economic differential in knowledge of danger signs of breast cancer among the women who were aware of breast cancer. The knowledge of different symptoms was less among marginalized classes like Scheduled Caste, Tribe and Other Backward Classes (SC or ST or OBC) group than in comparison to the other higher caste groups. A greater proportion of women, who were working had knowledge of different signs and symptoms of breast cancer than in comparison to women who were not working. It was also observed from the study that unmarried women had greater knowledge of all symptoms than in comparison to married women. No clear differential was found among age groups of women. Around half of the women believed ‘breast cancer means losing one’s breast’. Most women knew that breast cancer is not communicable (Table  3 ).

Knowledge of risk factors

Understanding the risk factors of BC may help women in taking preventive measures. In this study, women who were aware of breast cancer ( N  = 234) were asked about the risk factors of breast cancer. The percentage of women who identified breast cancer risk factors are shown in Fig.  3 . Most women believed consumption of excess tobacco (45%) and alcohol (44%) leads to breast cancer followed by risk factors like past history of BC (39%), no breastfeeding (39%), consumption of high fat foods (34%) and family history (31%). The knowledge of important biological risk factors like early age of menstruation (6%) and late menopause (10%) were very low among the women, although they had heard of breast cancer.

Percentage women who identified the risk factors of breast cancer

The socio-economic differentials showed that with an increase in age of women, the knowledge of different risk factors goes down (Table  4 ). Further, the risk factors knowledge was slightly higher among higher educated women compared to the women who had education till secondary school (10th standard). Women from nuclear family, not working and married woman had lower knowledge of most of the risk factors than in comparison to women from joint family, working and unmarried women respectively. However, the overall knowledge of risk factors was low among all women even though they are aware of breast cancer.

Knowledge and practice of breast examination

Of all 480 women, only 6.5% of women knew that breast cancer can be detected through Breast Self-Examination (BSE). Around two out of five (42%) women said cancer in breast can be detected through clinical examination (Fig.  4 ). Our results showed that around 10% of the women had undergone breast cancer screening. However, only 3.1% were trained in BSE and 2.5% of them were performing BSE. Around 2% of the women were performing BSE monthly (Fig.  5 ). Almost all women (99.4%) were interested to learn BSE procedure besides three women who were shy of it (not shown in figure).

Percentage of women who are aware of breast cancer screening

Percentage of women who have undergone screening of breast cancer and performing self-examination of breasts

This study found that breast cancer knowledge among the women in the study area was poor. Only less than half of the women were aware of breast cancer. This proportion was found to be consistent with two of the studies in India conducted in Mumbai (2009) and Delhi (2015) and one studies conducted in Addis Ababa, Ethiopia [ 15 , 19 , 25 ]. On the contrary, a recent study in Mumbai among 18–70 years of women found higher (71%) proportion of knowledge about breast cancer symptoms [ 26 ]. Television was found to be the most important source of breast cancer awareness. Our analysis of these 480 women found education as one of the crucial socio-economic factors that influences breast cancer awareness in Mumbai. Our bivariate and multivariate results have also shown consistent results on educational level and breast cancer awareness. A study by Dey et al. (2015) in Delhi also found an association between education and breast cancer awareness [ 15 ].

It is important to note that though half of the women were aware of breast cancer, the knowledge of different symptoms was low among these women. Lump in breast is considered as danger sign by most of the women whereas more than half don’t think abnormal discharge/blood, change in shape or size, and change in colour of nipple as danger signs of breast cancer. Another study in Vikroli, Mumbai also found similar results with a very low percentage of women saying the change in shape/ size of breast, discharge from nipple and inverted nipple as danger signs of breast cancer [ 17 ]. The study by Somdatta and Baridalyne [ 16 ] also found similar outcomes in a resettlement colony of Delhi. In this study, better knowledge of danger signs or symptoms of breast cancer is observed among higher educated and working women than lower educated and not working women respectively. Breast cancer means losing one’s breast(s) was the most common misconception among women.

Like many other Indian studies, this study found the knowledge of risk factors was very low [ 5 , 15 , 16 , 17 , 25 ]. The women in the study identified excessive consumption of tobacco, alcohol consumption and past history as most important risk factors of breast cancer. However, very few women in the community were aware of the risk of breast cancer due to disruption in biological clock like early menarche, late menopause, and hormonal therapy. Further, it is found knowledge of preventable risk factors like hormone replacement therapy, first baby after the age of 30 years, obesity, and use of oral contraceptive pills were low among participants. In this study, we also observed low knowledge of breast screening procedure among women like self-breast examination and mammography. The practice of BSE was very low because they were not trained to about the procedures.

This study is limited to one low socio-economic area of Mumbai, therefore, cannot be generalized to other community. The knowledge of signs, symptoms and risk factors depend on the comprehension capability of the participants during the data collection. Further, the study is cross-sectional in nature and therefore, it is not possible to get any causal relationship between dependent and independent variables.

This study aimed to assess breast cancer awareness and knowledge of danger signs, symptoms, risk factors and concluded that knowledge of danger signs and risk factors of breast cancer among women in the community was low. Considering the fact that breast cancer has grown as an epidemic in the country, lower knowledge of symptoms and signs may lead to delay in treatment seeking among the women. Although further studies are required at the national level, the lower knowledge of breast cancer among women in one of the advanced metropolises in India calls for greater effort to enhance knowledge of women at the regional and national level. This study calls for intervention to enhance and improve knowledge of breast cancer among women in the particular region with a special reference to women with low educational level and marginalised community. Effective media platform like television can be used to promote breast cancer awareness and breast self-examination practices. Advocacy and health education related to breast cancer awareness and screening methods and their accessibility needs to be strengthened in government programme with focus in lower socio-economic areas. Further, preparing appropriate and specific content for health education with an emphasis on preventable risk factors and lifestyle modification will enhance the awareness level and strengthen practices for prevention and early detection breast cancer.

Availability of data and materials

The raw data used in this research is available with the researchers. Please send your inquiries to the corresponding author.

Abbreviations

Breast Cancer

Global Cancer Incidence, Mortality and Prevalence

Breast Self-Examination

Clinical Breast Examination

Scheduled Caste

Scheduled Tribe

Other Backward Classes

Adjusted Odds Ratio

Confidence Interval

United Kingdom

Body Mass Index

Municipal Corporation of Greater Mumbai

Maharashtra Housing and Area Development Authority

Indian Council of Medical Research

National Institute for Research in Reproductive Health

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Acknowledgements

The authors are also thankful to the Director, ICMR-NIRRH and collaborative partners-Tata Memorial Hospital and Municipal Corporation of Greater Mumbai (MCGM) for all support to conduct the study. We acknowledge the contribution of the data collectors and thank the participants of the study for their time and co-operation.

Authors received no specific funding for this paper. However, the main study received financial support from the Department of Health Research, Government of India (R.11012/06/2018-HR). The funding agency had no role in the design the study, collection, analysis, and interpretation of data and in writing the manuscript.

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Department of Biostatistics, Indian Council of Medical Research-National Institute for Research in Reproductive Health (ICMR-NIRRH), Jehangir Merwanji Street, Parel, Mumbai, 400012, India

Ranjan Kumar Prusty, Shahina Begum & D. D. Naik

Department of Clinical Research, ICMR-NIRRH, Jehangir Merwanji Street, Parel, Mumbai, 400012, India

Anushree Patil

Department of Preventive Oncology, Centre for Cancer Epidemiology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, 400012, India

Sharmila Pimple & Gauravi Mishra

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Contributions

SB & RKP conceived, designed, and performed the experiments and analyses. RKP wrote the first draft of the manuscript and contributed reagents/materials/analysis tools: SB, AP, DDN, SP and GM have read and revised the manuscript. All authors read and approved the final manuscript.

Authors’ information

Shahina Begum (Corresponding Author) is Scientist ‘E’ and Head at Department of Biostatistics, ICMR-NIRRH, Mumbai, India. [email protected]

Ranjan Kumar Prusty is Scientist ‘B’ at ICMR-NIRRH, Mumbai, India

Anushree Patil is Scientist ‘E’ at ICMR-NIRRH, Mumbai, India

DD Naik is Senior Technical Officer-3 at ICMR-NIRRH, Mumbai, India

Sharmila Pimple and Gauravi Mishra are Professors at Department of Preventive Oncology, Centre for Cancer Epidemiology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India.

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Prusty, R.K., Begum, S., Patil, A. et al. Knowledge of symptoms and risk factors of breast cancer among women: a community based study in a low socio-economic area of Mumbai, India. BMC Women's Health 20 , 106 (2020). https://doi.org/10.1186/s12905-020-00967-x

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ORIGINAL RESEARCH article

Evaluation of knowledge, perception, and risk awareness about breast cancer and its treatment outcome among university of gondar students, northwest ethiopia.

• School of Pharmacy, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia

Background: Breast cancer is among the most common life-threatening public health problems of global concern including Ethiopia. Knowledge and awareness about the disease will help to reduce the number of cases who present at late stages of the disease. The objective of this survey was to assess the knowledge, perception and risk awareness about breast cancer among female medical and health science students of University of Gondar, Ethiopia.

Methods: A cross sectional survey was conducted from May 03 to June 01, 2017 at University of Gondar, Ethiopia. Three hundred students were proportionally selected from nine departments using simple random sampling method. Using a structured questionnaire data on risk factors, symptoms and perception about breast cancer and its management approach was collected. Data were entered to and analyzed using SPSS version 21.

Results: A total of 300 students had fully completed the survey making the response rate 95.24. The participants' mean age was 21.4 years with the standard deviation (SD) of 2.13 years. The overall level of knowledge on breast cancer was low. Majority of the participants were unaware for complex risk factors such as first child after the age of 30 years (51%), early onset of menses (55.3%), and menopause after the age of 55 years (47.7%) are liked with breast cancer even though they acknowledged old age, family history, and smoking as possible risk factors for breast cancer. Pain in the breast region, change in the shape of the breast, and nipple discharge were the most frequently correctly identified symptoms of breast cancer. Majority of the study participants had also correct beliefs about breast cancer management and its outcomes. however, they had negative perception of breast cancer treatment by considering it to be a long-term and painful process. In binary logistic regression analysis department ( p = 0.000) and year of study ( p = 0.008) were found to be an independent predicting factors for knowledge among the study participants.

Conclusions: The overall level of knowledge on breast cancer and clinical breast examination guidelines was found to be low even though majority had positive perception toward the treatment and its outcomes. Hence, intensive breast health awareness campaign, which should also stress on the importance of early detection and reporting, is necessary to improve the knowledge about breast cancer.

Introduction

Breast cancer is one of the top most public health concern jeopardizing the lives of many peoples worldwide ( 1 , 2 ). This kind of cancer is malignant by nature endangers breast tissue, and may involve either the tubules carrying milk or ducts which produce the milk. This type of disease can metastasize to distant areas or invade surrounding tissues. Commonly, the disease happens in women population although males may also suffer from it ( 3 ).

Globally, the incidence of breast cancer has increased from 641 000 in 1980 to 1 643 000 in 2010 with an annual increment of 3.1% ( 4 ). Different reports revealed that in sub-Saharan African and other resource limited countries the rate of occurrence of breast carcinoma is significantly increasing ( 5 , 6 ). The overall incidence in Ethiopia is also increasing, it is estimated around 10,000 women and men taking in consideration that more number of cases were unreported since women from country side usually prefer to go to cultural treatment providers than looking for health care institution ( 7 ). Some of contributing factors implicated in steady rise in breast cancer incidence in developing countries are widespread urbanization, changing patterns of reproductive and environmental risks factors, obesity, decreased physical activity, and increasing life expectancy ( 8 , 9 ). Since 1980, the mortality of breast cancer has also increased from 250,000 to 425,000 in 2010. About 60% of deaths from breast cancer are occurring in low income countries ( 4 ).The high mortality associated with breast cancer in countries like Ethiopia is most importantly due to knowledge shortage about the disease that may leads to late diagnosis ( 10 ).

The exact reasons for the occurrence of breast cancer have not been fully understood. However, numerous researchers have identified a number of predictors that can increase one's likelihood of getting breast cancer. They called them risk factors and includes family and individual backgrounds of breast cancer; delayed menopause (>55 years); early menarche (<12 years); late age at first full-term pregnancy (>30 years); alcohol use; aging; never breastfeeding a child; exposure to contraceptives; tobacco smoking; high fat diet; obesity (postmenopausal); recent and long-term consumption of hormonal replacements; physical inactivity; high-dose x-ray to chest ( 11 , 12 ).

Although in developed countries, screening of such malignant tumor is usually performed using mammograms, the access to most women in sub Saharan countries are limited. From the existing situation it is uncertain to have amendments in the upcoming days ( 13 ). Breast self-examination (BSE) is the mere, reasonable and practical option of screening for women living in Africa in case of non-appearance of mammography ( 13 , 14 ). With applicable training of BSE along with clinical breast examination and comprehensive health education of the disease, it is likely to early detect the disease. Women who repeatedly do BSE tend to accustom both the feeling and appearance of their breasts this in turn will help them to early identify any changes. However, if it is done improperly, there might be untrue positive or negative findings associated with poor BSE and this may raise a great disappointment to undergo mammographic screening even in the set up where it is available and easily accessible ( 15 ).

In Ethiopia poor awareness is the core concern and there is also stigma and misconceptions/understanding about cancer, that all cancer cases are incurable. Associated with this little work was done so far to promote the awareness that most cancer cases can be prevented, even cured if detected early, and quality of life can also be improved ( 16 ).

As the principal focus of the present study was students, it strengthens cancer detection and prevention strategies at an early age, creates education opportunities for shaping health behaviors into adulthood and also encourage discussions between students and their guardians as well as relatives. Therefore, the purpose of the present survey was to explore the knowledge, perception and risk awareness toward breast cancer among female medical and health science students of University of Gondar, Ethiopia.

Study Design and Setting

An institutional based cross sectional study was employed among female medical and health science students of University of Gondar (UOG). UOG is among the first born universities in Ethiopia and located 737 km from the capital of Ethiopia, in northwest direction. It has 5 campuses such as Atse Tewodros, Maraki, College of Medicine and Health Sciences (CMHS), Atse Fasil, and Meles Zenawi. At present, with the nine academic offices it offers about 56 undergraduate and 64 postgraduate programs in regular, distance, extension and summer programs.

Study Samples

Female students who had interest to complete the self-administered questionnaire were included. However, students with already existing disease and unable to understand the questionnaire were excluded.

Sample Size Determination and Sampling Technique

Appropriate sample size was estimated using a single proportion formula ( 17 )

Where n is the need sample size; d , marginal error ( d = 0.05); Z , the required degree of accuracy at 95% confidence level, which is 1.96; P = 0.5 (50%) level of knowledge, as there was no study conducted in the study area to the best of literature search made. Using the above formula, the sample size was calculated as follows:

Since the sample was drawn from the gross population of 1463, which is <10,000, the required final sample size was determined after applying the correction factor;

Considering 5% for probable non-respondent, the required final sample size was 315.

Sampling Technique/Procedure

The final sample was distributed proportionally across different departments. Using simple random sampling technique the required samples from each department were recruited in the study (Figure 1 ).

Figure 1 . A flow chart describing the sampling technique, UOG, 2017.

Data Collection Technique and Management

Three principal investigators were responsible for conducting the data collection. The data were obtained through self-administered questionnaire. The tool used was adopted from prior studies conducted in this area and prepared in English ( 18 – 23 ). The data collection tool has three sections: The first part includes socio-demographic variables while the second one comprises knowledge of breast cancer risk factors, symptoms and screening tests and the third part focuses on perception of management and outcomes. Participants' response was given 1 point for correct and zero for incorrect answer or do not know. The knowledge status was considered as “low,” “moderate,” and “high” if the scores fall in the range of 0–49, 50–79, and 80–100%, respectively ( 24 ). Likert scale of 1–5 was also employed to rate the responses of participants regarding perception related questions. It was also pretested on 25 participants who were not included in the final analysis before the commencement of actual data collection. Moreover, training on the familiarization of the instrument and strategies to approach the students were provided for the investigators.

Data Entry and Analysis

The collected data using quantitative method was entered to and analyzed using Statistical packages for social sciences (SPSS) version 21 statistical software. Frequencies, percentages, tables, flow chart were used to describe study variables. Binary logistic regression analysis was done to examine the association among different variables. For determining statistically significant associations, P < 0.05 and confidence interval (CI) of 95% were used as cut points.

Ethical Considerations

The study was ethically approved by the ethical review committee of School of Pharmacy (SoP), University of Gondar (UoG) with an approval number of UoG-SoP-140/2017. Informed consent was gained from each participant before the start of the study. They were also informed that involvement in the study was fully voluntarily and withdrawal at any stage if they refused to participate was assured. Information obtained from the survey was kept confidential. In addition, patient identifiers were not used.

Socio-Demographic Characteristics of the Participants

In the current study, out of the total interview guides/questionnaires of sample of 315 students who were interviewed 300 were included in the analysis, and 15 encounters were excluded due to incompleteness making the response rate 95.24%. The average age of the study respondents were 21.4 years with the standard deviation (SD) of 2.13 years.

More than two third 188 (62.7%) of the participants had no previous participation in breast care awareness. However, they had interest to participate in activities that encourages breast cancer awareness 234 (78.0%) (Table 1 ).

Table 1 . Distribution of participants by socio-demographic characteristics, UOG, 2017.

Knowledge of Breast Cancer Symptoms, Risk Factors, and Screening Test

More than two third of the participants acknowledged old age, family history, and smoking as possible risk factors for breast cancer. Majority of the participants were unaware for complex risk factors such as first child after the age of 30 years (51%), early onset of menses (55.3%), and menopause after the age of 55 years (47.7%) are liked with breast cancer. Pain in the breast region, Change in the morphology/shape of the breast and nipple discharge were the most frequently correctly identified symptoms of breast cancer. Moreover, 168 (56.0%) of the participants were aware about once a month recommendations for practicing breast self-examination (BSE) and 108 (36%) for once a year clinical breast examination (CBE) (Table 2 ).

Table 2 . Participants' response to important knowledge related questions, UOG, 2017.

The overall level of knowledge was described by nineteen questions on breast cancer for general knowledge, risk factors and symptoms of breast cancer. Although the overall level of knowledge on breast cancer was low, high level of knowledge was observed in questions related to general knowledge about breast cancer 70 (23.3%) (Table 3 ).

Table 3 . Knowledge about breast cancer, UOG, 2017.

Perception Toward Breast Cancer Treatment and Its Outcomes

Majority of study participants had correct beliefs about breast cancer management and its outcomes. however, they had negative perception of breast cancer treatment by considering it to be a long-term and painful process (Table 4 ).

Table 4 . Perception toward breast cancer treatment and its outcomes, UOG, 2017.

Predictors of Knowledge of Breast Cancer Among the Participants

In binary logistic regression analysis department and year of study were found to be an independent predicting factors for knowledge among the participants. Students in pharmacy department (AOR = 0.839, CI = 0.312–2.255) were found to have 16.1% less likely to have good knowledge of breast cancer compared to public health officer students. On the other hand, students under first year of study (AOR = 2.661, CI = 0.407–17.389) were found to have 1.661 times more likely to have poor knowledge of breast cancer compared to fifth year students (Table 5 ).

Table 5 . Predictors of knowledge of breast cancer among the participants, UOG, 2017.

It is an unconcealed evidence that breast cancer turn out to be one of the frequently occurring cancers among female population of Ethiopia and barriers associated with detection and management of the case decreases survival rates ( 1 , 25 ). The present study indicates that huge number of the study respondents had no previous involvement in breast care awareness. However, they had interest to involve in activities to encourage breast cancer awareness. This finding concurs with the report from United Arab Emirates ( 19 ).

This study stated that, beyond two third of the study subjects revealed to have low overall knowledge toward risk factors, general knowledge, and clinical manifestations of the malignant tumor, which was similar with the reports from Malaysia, Saudi, Egypt, and Nigeria ( 21 , 26 – 28 ). Many female students in such higher institutions are unacquainted of clinical breast examination (CBE), the predictors, and early presentation of the tumor. This might be the cause for the delayed presentation of the disease in developing countries. Therefore, it is crucial to provide comprehensive breast cancer and health awareness programs for female youngsters.

Bulk of the respondents acknowledged old age, family history, and tobacco use as potential predisposing factors for the tumor. Most of the participants were also unaware of complex risk factors such as first child after the age of 30 years (51%), early onset of menses (55.3%), and menopause after the age of 55 years (47.7%) are liked with breast cancer. This finding was comparable with studies done in Malaysia, Egypt, Oman and Britain ( 18 , 22 , 23 , 29 ).

Most of the study participants identified pain in the breast region as a symptom for breast cancer followed by swing in the morphology/shape of the breast and nipple discharge. However, more than one third of the respondents had less knowledge about under armpit lump and painless breast lump as cautioning signs of the disease. This finding concurs with the reports from Malaysia, Egypt, Nigeria, and Oman ( 18 , 22 , 23 , 28 ). However, it was higher when matched to the findings from Madawolabo ( 30 ). This could be justified as the respondents were merely from medical and health science streams, it was expected that awareness about manifestations of the disease to be good when matched to other technology campuses in the university.

Numerous respondents had the factual perception about breast cancer management and its outcomes. however, they had negative view of the tumor treatment by seeing the length of treatment and painful process, which was similar with the report from Malaysia and Nigeria ( 18 , 28 ). This finding suggest the need for customized educational interventions using different lines such as social media, distribution of leaflets, television/ radio broadcasts and proper counseling as tools for improving the knowledge and perception about the tumor and the treatment outcomes.

Binary logistic regression analysis was performed and factors such as department and study year were recognized as independent predictors for disease related knowledge among the study participants. Pharmacy students (AOR = 0.839 CI = 0.312–2.255) were 16.1% less likely to own good knowledge of breast cancer when equated to public health officer students. The study also mentioned that the odds of having poor knowledge toward the disease were 1.661 times higher among students enrolled under first year of study (AOR = 2.661, CI = 0.407–17.389) compared to fifth year students. This might be due more exposure and familiarization about breast cancer and related health issues in different courses, trainings and seminars will be embraced as academic year goes up.

As a drawback, although this research is the first in its kind in the study setting that can be used as an input for implementing basic projects, it is conducted only in one institution that the generalization to all over university students will be in question. With this, we highly recommended a large scale and multi centered survey that comprises diverse participants to validate our output and provide more representative findings.

Conclusions

In this study, the overall level of knowledge on breast cancer was low. Majority of the participants were unaware for complex risk factors such as first child after the age of 30 years, early onset of menses, and menopause after the age of 55 years are liked with breast cancer. However, small proportion of the participants were aware about clinical breast examination guidelines. Pain in the breast region, change in the shape of breast and nipple discharge were the most frequently correctly identified symptoms of breast cancer. On the other hand, majority of the participants acknowledged old age, family history, and smoking as possible risk factors for breast cancer and they had also positive perception toward breast cancer treatment and its outcomes. Department and year of study were found to be an independent predicting factors for knowledge among the participants.

Implications

Bearing in mind the greatest prominence of knowledge, perception and risk awareness about such tumor, institutions and different stakeholders working on cancer should offer a tailored health promotion and awareness creation to university youngsters, in line with cultivating facilities that let them do the screening examination regularly. In addition, the country ministry of education and health has to work on incorporating capacity building regular trainings regarding such disease avoidance and early detection in such organizations.

Author Contributions

All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Keywords: breast cancer, awareness, self-examination of breast, treatment-outcome, Ethiopia

Citation: Gebresillassie BM, Gebreyohannes EA, Belachew SA and Emiru YK (2018) Evaluation of Knowledge, Perception, and Risk Awareness About Breast Cancer and Its Treatment Outcome Among University of Gondar Students, Northwest Ethiopia. Front. Oncol . 8:501. doi: 10.3389/fonc.2018.00501

Received: 09 August 2018; Accepted: 15 October 2018; Published: 02 November 2018.

Reviewed by:

Copyright © 2018 Gebresillassie, Gebreyohannes, Belachew and Emiru. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Yohannes Kelifa Emiru, [email protected]

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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The figure shows the percentage of women who answered that having the other risk factor put a woman at greater risk compared with dense breasts. Family history is defined as having a mother or sister who has or had breast cancer. Other race included women identifying as mixed race or another race or ethnicity. Data were missing for the following categories: being overweight or obese, 23; having 1 or more drinks of alcohol per day, 23; first-degree family history of breast cancer, 15; never having children, 27; having a breast biopsy, 32; and race and ethnicity, 1.

eAppendix 1. Breast Cancer Risk Factors

eAppendix 2. Survey Instrument Content

eAppendix 3. Interview Guide

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Beidler LB , Kressin NR , Wormwood JB , Battaglia TA , Slanetz PJ , Gunn CM. Perceptions of Breast Cancer Risks Among Women Receiving Mammograph Screening. JAMA Netw Open. 2023;6(1):e2252209. doi:10.1001/jamanetworkopen.2022.52209

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Perceptions of Breast Cancer Risks Among Women Receiving Mammograph Screening

• 1 The Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire
• 2 Section of General Internal Medicine, Boston University Chobanian and Avedesian School of Medicine, Boston, Massachusetts
• 3 Department of Psychology, University of New Hampshire, Durham
• 4 Department of Radiology, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts
• 5 Dartmouth Cancer Center, The Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire

Question   How do women perceive the breast cancer risk associated with breast density, and how do they plan to mitigate their risk?

Findings   In this qualitative study of women aged 40 to 76 years, family history was perceived as the greatest risk factor for breast cancer. In interviews, few women perceived breast density as a risk factor, and one-third thought that they could not take any actions to reduce their breast cancer risk.

Meaning   Despite laws that require women to be notified about breast density, women did not describe a strong understanding of the risk associated with breast density relative to other breast cancer risk factors.

Importance   Breast density is an independent risk factor for breast cancer. Despite the proliferation of mandated written notifications about breast density following mammography, there is little understanding of how women perceive the relative breast cancer risk associated with breast density.

Objective   To assess women’s perception of breast density compared with other breast cancer risks and explore their understanding of risk reduction.

Design, Setting, and Participants   This mixed-methods qualitative study used telephone surveys and semistructured interviews to investigate perceptions about breast cancer risk among a nationally representative, population-based sample of women. Eligible study participants were aged 40 to 76 years, reported having recently undergone mammography, had no history of prior breast cancer, and had heard of breast density. Survey participants who had been informed of their personal breast density were invited for a qualitative interview. Survey administration spanned July 1, 2019, to April 30, 2020, with 2306 women completing the survey. Qualitative interviews were conducted from February 1 to May 30, 2020.

Main Outcomes and Measures   Respondents compared the breast cancer risk associated with breast density with 5 other risk factors. Participants qualitatively described what they thought contributed to breast cancer risk and ways to reduce risk.

Results   Of the 2306 women who completed the survey, 1858 (166 [9%] Asian, 503 [27%] Black, 268 [14%] Hispanic, 792 [43%] White, and 128 [7%] other race or ethnicity; 358 [19%] aged 40-49 years, 906 [49%] aged 50-64 years, and 594 [32%] aged ≥65 years) completed the revised risk perception questions and were included in the analysis. Half of respondents thought breast density to be a greater risk than not having children (957 [52%]), having more than 1 alcoholic drink per day (975 [53%]), or having a prior breast biopsy (867 [48%]). Most respondents felt breast density was a lesser risk than having a first-degree relative with breast cancer (1706 [93%]) or being overweight or obese (1188 [65%]). Of the 61 women who were interviewed, 6 (10%) described breast density as contributing to breast cancer risk, and 43 (70%) emphasized family history as a breast cancer risk factor. Of the interviewed women, 17 (28%) stated they did not know whether it was possible to reduce their breast cancer risk.

Conclusions and Relevance   In this qualitative study of women of breast cancer screening age, family history was perceived as the primary breast cancer risk factor. Most interviewees did not identify breast density as a risk factor and did not feel confident about actions to mitigate breast cancer risk. Comprehensive education about breast cancer risks and prevention strategies is needed.

Dense breasts, in which breasts are composed of more glandular tissue relative to fatty tissue, is an independent, nonmodifiable risk factor for breast cancer and can mask cancer on mammograms. 1 Dense breast tissue is present in 40% to 50% of women undergoing screening mammography 2 and is associated with a 1.2 to 4.0 times higher risk of breast cancer (depending on degree of density) compared with a 2.0 times higher risk associated with a first-degree family history of breast cancer. 3 - 6 Other known risk factors include obesity, alcohol consumption, parity, and having a prior breast biopsy (eAppendix 1 in Supplement 1 ). 3 , 7 , 8 Although how much each risk factor or combination of factors affects overall breast cancer risk has not been completely characterized, 7 knowledge about personal risk is necessary to promote engagement in prevention, particularly for modifiable contributors, such as alcohol consumption and obesity.

Aiming to increase awareness and empower women to make informed choices about supplemental screening, laws enacted across 38 states mandate that women receive written notification about their personal breast density and its potential health implications. 9 Although laws vary among states, 9 they share an underlying goal of informing women about their personal breast cancer risk to promote informed decision-making about breast cancer screening and early detection.

Prior studies 10 - 17 have evaluated the association of breast density notification laws with women’s awareness of their individual breast density, masking bias, and the risks associated with breast density. Qualitative studies have found that few women are aware of the legislation around breast density notification, 15 that some women find breast density notifications to be confusing, 17 and that, although most women understand that breast density could mask cancer on a mammogram, few know that breast density is an independent breast cancer risk. 13 Cross-sectional surveys have found variation in women’s knowledge about breast density as a risk factor 10 - 12 , 14 , 16 ; variation in knowledge across racial and ethnic groups, income, and educational levels 11 , 14 ; that most women were aware of masking bias 11 , 14 , 16 ; and that women in states that mandated breast density notification were more likely to report having dense breasts. 14

Although the current literature explores women’s knowledge about breast density, a systematic review 18 noted that little is known about whether women understand the risk associated with breast density compared with other risk factors or their approaches to mitigating risk. We used a national survey and qualitative interviews to examine how women perceive breast density’s cancer risk relative to other breast cancer risk factors and their understanding of actions they could take to reduce breast cancer risk.

This mixed-methods qualitative study included survey data from a national, random-digit-dialing telephone survey coupled with semistructured interviews with a subset of survey respondents. Survey questions examined women’s perception of breast density in relation to other known breast cancer risks; interviews explored women’s understanding of breast cancer risk factors and actions to mitigate risk. This mixed-methods approach allowed us to examine the scope of awareness and understanding. On the basis of prior literature demonstrating differences in perceptions by sociodemographic characteristics, 11 , 14 we examined whether risk perceptions varied by self-reported race and ethnicity and by literacy level (high literacy [HL] vs low literacy [LL]). This study was reviewed by the Boston University Medical Campus Institutional Review Board, which determined that the study met federal exemption criteria and provided a waiver of documentation of informed consent. Approval was for the qualitative interviews (survey work was conducted by an external survey firm) and at the time of transcription. All interview data was deidentified. The study followed the Standards for Reporting Qualitative Research ( SRQR ) for reporting qualitative data. 19

The sampling frame consisted of 2306 participants who completed a national, random-digit-dialing survey of the effect of states’ breast density notification laws on knowledge about breast cancer risks associated with breast density. Eligible participants were aged 40 to 76 years, reported having undergone mammography in the prior 2 years, had no history of breast cancer, and had heard of breast density. Within the population-based sampling, efforts were made to ensure a sufficient sample of women from diverse racial and ethnic backgrounds, from states with and without breast density notification laws, and with lower literacy levels, as detailed in prior publications. 20 , 21 Participants were asked in the survey to self-identify their race or ethnicity. We collected race and ethnicity data to allow for oversampling across some groups to ensure that we could conduct analyses that compared findings across groups.

After completing the survey, women who reported knowing their breast density were invited to participate in a qualitative interview. Those who responded affirmatively were called to schedule an interview. We purposively sampled equal numbers of women who identified as Black, Hispanic, White, or other race or ethnicity as well as those with HL vs LL. In the survey, participants were asked to self-identify their race from a list that included Asian, Black or African American, Native American, Pacific Islander, White, mixed race, or some other race. For these analyses, anyone who responded that they were Native American, Pacific Islander, mixed race, or some other race were classified as other race. For the qualitative interviews, we included respondents who were Asian in the other race category.

Breast density awareness and breast cancer risk questions were adapted from measures used in prior surveys, 10 , 11 , 22 with modified measures tested by patient advisory group members. Advisory group members also reviewed the interview guide. The survey firm, SSRS, conducted all surveys using a standardized interview approach (eAppendix 2 in Supplement 1 ). The cooperation rate for the overall survey was 85%. 20 Survey administration spanned July 1, 2019, to April 30, 2020, and took approximately 10 minutes. Qualitative interviews were conducted from February 1 to May 30, 2020, and lasted 30 to 45 minutes. Qualitative interviews followed a flexible, semistructured interview guide (eAppendix 3 in Supplement 1 ) and were audiorecorded and transcribed. All data were collected via telephone by trained interviewers.

This mixed-methods qualitative study focused on women’s perceptions of breast cancer risks, examining how women rate certain risks relative to the risk of breast density. Women were asked to compare the risk of breast density with 5 other breast cancer risk factors (having a first-degree relative with breast cancer, being overweight or obese, having more than 1 alcoholic drink per day, never having children, or having a prior breast biopsy). A review of data from the first 448 survey participants revealed that wording of the risk perceptions questions was confusing. We revised the questions and excluded those participants from analyses due to identified measurement error and incompatibility of responses with subsequent risk questions. For each risk factor, participants were asked the question, “Which do you think puts someone at greater risk for developing breast cancer? Having dense breasts or…” Risk factors were elicited in a random order to minimize ordering bias.

We characterized the proportion of women who said having dense breasts puts someone at a greater risk for developing breast cancer vs the alternative risk factor or “don’t know”; participants with missing responses were excluded from analyses (<1%). Bivariate χ 2 analyses assessed whether the proportion of women who said having dense breasts puts someone at greater risk for developing breast cancer was associated with participants’ race and ethnicity (coded as Asian, Black, Hispanic, White, and other category not listed) or literacy level (HL or LL). Low literacy was defined as either having less than a high school education or reporting sometimes, often, or always needing assistance to complete medical forms using the validated Single Item Literacy Screener. 23 We used SPSS statistics software, version 26 (IBM Inc). 24 Statistical significance was defined at α = .05. We followed the American Association for Public Opinion Research ( AAPOR ) reporting guidelines for survey data. 25

Women were asked in an open-ended fashion what they thought contributed to breast cancer risk and how they could reduce their breast cancer risk. To organize and support analyses, we developed an analytic memo that described all observed themes. 26 We used a matrix coding approach to guide development of themes and justify inclusion or exclusion of interviewees within themes. 27 This approach includes arranging data within a table where individual participants represent rows and themes represent columns. We analyzed whether themes varied across literacy levels or across racial and ethnic groups. Qualitative analyses were overseen by a doctoral-level health services researcher (C.M.G.) with expertise in qualitative methods. Two masters-level trained research coordinators and 1 doctoral student participated in data collection and analysis, including co-coding and consensus determination meetings.

Of the 2306 women who responded to the survey, 1858 (166 [9%] Asian, 503 [27%] Black, 268 [14%] Hispanic, 792 [43%] White, and 128 [7%] other race; 358 [19%] aged 40-49 years, 906 [49%] aged 50-64 years, and 594 [32%] aged ≥65 years) completed the revised risk perception questions and were included in the analysis ( Table 1 ). In comparing risk factors with the risk associated with breast density, 1706 women (93%) viewed family history of breast cancer as the greater risk, and 1188 (65%) felt that being overweight or obese was a greater risk than breast density. Half of respondents thought that breast density was a greater risk than not having children (957 [52%]), having more than 1 alcoholic drink per day (975 [53%]), or having a prior breast biopsy (867 [48%]) ( Figure ). A higher proportion of women with LL compared with women with HL rated breast density as a higher risk than family history (13% vs 7%; χ 2 1  = 12.99, P  < .001), alcohol consumption (60% vs 53%; χ 2 1  =  5.41, P  = .02), and never having children (60% vs 51%; χ 2 1  = 7.39, P  = .007). A higher proportion of Black women (290 [58%]) and Hispanic women (153 [58%]) rated dense breast as a higher risk than alcohol consumption compared with women of other races (χ 2 4 13.63, P  = .009). A total of 289 Black (58%) and 153 Hispanic (58%) women also rated dense breasts as a higher risk than nulliparity than women who identified as Asian (74 [45%]), White (377 [48%]), and other race (64 [52%]) (χ 2 4  = 17.48, P  = .002).

Among 61 women interviewed, few women perceived breast density as contributing to their risk of developing breast cancer. Most women correctly noted that breast density could make mammograms harder to read: “It’s difficult to detect subsequent lumps or potential problem areas because of the dense breast tissue.” (Black woman, HL, respondent 7). When asked about their personal risk factors for breast cancer, few women noted that breast density could be a risk factor. One woman described her concern by saying, “Maybe 10% more worried than I was before because of the dense tissue issues. Just a slight uptick, but it’s not overwhelming” (Hispanic woman, HL, respondent 17).

Women most frequently and confidently emphasized family history of cancer or genetic factors as contributing to their own breast cancer risk ( Table 2 ), and many viewed this as conferring very high levels of risk. One woman estimated her own risk as “probably 50/50 at this point since my mother had breast cancer” (Black woman, HL, respondent 5). Concurrently, women who had no known family history seemed to minimize the possibility of developing cancer: “I’m not worried about it because it does not run in my family. So I don’t have to worry about dodging that bullet” (Hispanic woman, LL, respondent 23).

Table 2 displays risk factors cited by women, ordered by the prevalence of the theme across participants. Reported risk factors included diet, lifestyle, smoking and environmental exposures, breast density, obesity, alcohol consumption, and reproductive history. Unlike family history, most women did not voice confidence in their understanding of other risk factors. Instead, they spoke about a series of behaviors and exposures that they perceived as related to their health overall: “We blame smoking for everything. So I’m sure smoking’s on there” (Black woman, HL, respondent 5). Few women stated that they had no knowledge of what breast cancer risk factors were: “I have no idea. All the stuff that’s been here on the news. This chemical, that chemical...” (Black woman, HL, respondent 8). We did not observe differences in understanding or perception of personal breast cancer risk by health literacy level or by racial or ethnic group.

When asked about actions that could reduce their breast cancer risk, many women described detection methods, such as breast self-examinations and mammograms, as prevention strategies. Among women who discussed mammograms or breast self-examinations, a small subset noted that screening methods would not prevent cancer but were useful for potentially detecting breast cancer earlier: “Well, if I go for my annual mammogram and do self-breast examination, I will catch whatever’s growing in my breast will be nipped in the bud...It will be taken care of before it gets out of control” (White woman, LL, respondent 54).

Women’s descriptions of risk mitigation focused on mammography, with descriptions conflating early detection and prevention. Other ideas for reducing personal breast cancer risk included improving diet, maintaining a healthy weight, quitting smoking, avoiding secondhand smoke, limiting alcohol, and exercising ( Table 3 ). Many women suggested behaviors that they thought could improve their overall health but expressed less certainty about the direct effect on their breast cancer risk: “I try to eat a healthier lifestyle, more in the vegetable fields, less in any kind of…dairy or red meat portions. I do exercise more, but I did that for my general health, not for breast cancer” (Hispanic woman, HL, respondent 17).

Many women (17 [28%]) stated that they were not sure if it was possible to reduce their breast cancer risk or that they did not know what actions they could take to reduce their risk: “Do people even know how to prevent breast cancer? I couldn’t even say” (woman of other race, HL, respondent 30). Neither health literacy level nor race or ethnicity appeared to differentiate how women perceived actions that they could take to reduce their breast cancer risk.

This mixed-methods qualitative study demonstrated that women perceived family history as the strongest risk factor for breast cancer, with mixed perceptions about other lifestyle or clinical risk factors in relation to breast cancer risk. Among interview respondents who knew their breast density, few women noted breast density as a breast cancer risk factor. Few women understood options for mitigating their personal breast cancer risk.

Despite breast density being associated with a 1.2 to 4 times higher risk of breast cancer, 1 , 5 , 6 few women perceived breast density to be a strong personal risk factor. This finding is not surprising because prior studies 11 , 14 have shown variable rates of women indicating that breast density contributed to breast cancer risk (23%-66%). Qualitative studies 13 , 17 , 28 , 29 of women receiving breast density notifications found that women did not fully understand the clinical term breast density . It is possible that notification language stressing the normality of dense breast tissue in the population confers a sense of reassurance that may contribute to the downplaying of breast density as a risk factor. 13 , 29

In both interviews and surveys, women perceived family history as highly deterministic of future breast cancer. Women without a family history believed they were safe or had limited risk based on this factor alone. Other studies 30 , 31 have similarly found that women with family histories of breast cancer perceived their personal risk of cancer to be higher than the estimated risk associated with their family history. The emphasis on family history may be in part a result of clinical elicitation of family and genetic risk factors, including the increased emphasis on genetic testing for BRCA1/2 genes, both clinically and in popular media. 32 , 33 A 2021 systematic review 34 found that in primary care, family history is often the only risk factor elicited to counsel patients on breast cancer risk. Thus, frequent health messaging around family history and breast cancer risk may play a role in how this sample of women perceived their own breast cancer risk. Interviewed women displayed little confidence in their ability to modify their cancer risk, suggesting a need for more comprehensive education about which risk factors are amenable to intervention.

Few women identified ways in which they could reduce their breast cancer risk. When mentioned, these actions included participating in regular screening, diet and exercise, and avoiding tobacco ( Table 3 ). Many women suggested that breast self-examinations were important to maintaining their breast health, but these examinations are no longer recommended because of a lack of evidence of benefit. 35 (p179) 36 Women also suggested actions that they thought were generally healthy lifestyle changes, but they were not confident these actions would alter their breast cancer risk. Women may benefit from general guidance and information about cancer prevention strategies, such as tools that can help patients understand overall cancer risk and prevention options. 37 Clinical treatments, such as chemoprevention agents, are available to reduce breast cancer risk for women at elevated risk (>1.7% 5-year risk as determined by a validated risk model) 38 , 39 but were not mentioned by any interviewees. This finding is not unexpected because chemoprevention is significantly underused by the eligible population, 40 - 42 despite being recommended for women at elevated risk. 43

This study has some limitations. Despite efforts to include a racially and ethnically diverse sample on the telephone survey panel, nonresponse bias could have influenced findings. The survey did not ask about women’s perception of the absolute risk associated with each risk factor, limiting our ability to draw conclusions about the accuracy of women’s risk perceptions. Interviewees reported being informed of their personal breast density, but we were unable to verify the nature or timing of this notification. We defined low literacy using a single-item literacy scale combined with educational level, which is an imprecise way to measure literacy, limiting our ability to draw conclusions about the direct effect of literacy on risk perception.

Our study, coupled with prior research, 12 , 14 , 18 , 20 suggests that understanding of breast density’s contribution to breast cancer risk remains underappreciated by many women. Most notifications encourage women to speak with their physicians, yet prior studies 15 , 44 - 47 found that many clinicians do not feel comfortable counseling on the implications of breast density and cancer risk. Efforts to communicate breast density in part are intended to align with evidence suggesting that breast cancer screening services should be tailored to personal risk to maximize the benefits and avoid undue harms, 48 - 50 rendering conversations about risk imperative. Women with dense breasts, and thus some elevated risk, are ideal candidates for risk assessment. Tools that incorporate breast density in risk measures, such as one from the Breast Cancer Surveillance Consortium, 51 , 52 can inform future screening behaviors, including the opportunity for supplemental screening. Supplemental screening not only can lead to increased rates of cancer detection but also may result in more false-positive results and recall appointments. 53 - 55 Because supplemental screening is not recommended for women at average risk, 55 clinicians should use risk assessment to guide discussions with patients about tradeoffs associated with supplemental screening.

Despite available guidance on breast cancer risk assessment to inform screening decisions, 56 , 57 such assessments are underused in primary care. 58 - 60 Reported barriers include inadequate time, lack of integrated tools, and uncertainty in interpreting results for decision-making. 58 A review 61 of interventions involving the use of risk assessment tools in primary care concluded that more comprehensive interventions that combined risk assessment with decision support were more likely to have an effect on behavior. In some cases, it may be beneficial to develop partnerships between primary care and radiology to help counsel women on appropriate supplemental screening and/or preventive measures. 62 In summary, future laws or regulations involving breast density notifications should ensure that communications promote a more comprehensive understanding of breast cancer risk to inform choices about screening and prevention.

Accepted for Publication: December 2, 2022.

Published: January 23, 2023. doi:10.1001/jamanetworkopen.2022.52209

Open Access: This is an open access article distributed under the terms of the CC-BY License . © 2023 Beidler LB et al. JAMA Network Open .

Corresponding Author: Christine M. Gunn, PhD, Dartmouth Cancer Center, The Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine, Dartmouth College, 1 Medical Center Dr, Williamson Translational Research Bldg, Level 5, Lebanon, NH 03765 ( [email protected] ).

Author Contributions: Dr Wormwood had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Kressin, Battaglia, Gunn.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Beidler, Gunn.

Critical revision of the manuscript for important intellectual content: Kressin, Wormwood, Battaglia, Slanetz, Gunn.

Statistical analysis: Wormwood.

Obtained funding: Kressin.

Supervision: Slanetz, Gunn.

Conflict of Interest Disclosures: Dr Battaglia reported receiving grants from Boston Medical Center during the conduct of the study. Dr Slanetz reported receiving royalties from Wolters-Kluwer outside the submitted work and serving as subspecialty chair of the American College of Radiology Appropriateness Criteria Breast Imaging Panels. Dr Gunn reported receiving grants from the American Cancer Society during the conduct of the study and receiving grants from the National Cancer Institute and consultation fees from Gilead Sciences outside the submitted work.

Funding/Support: This study was supported by grant RSG-133017-CPHPS from the American Cancer Society (principal investigator, Dr Kressin). Dr Gunn was funded in part by the National Cancer Institute (K07CA221899; principal investigator, Dr Gunn).

Role of the Funder/Sponsor: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication.

Disclaimer: The views expressed here do not necessarily reflect the views of the American Cancer Society.

Data Sharing Statement: See Supplement 2 .

Additional Contributions: Ariel Maschke, MA, Magdalena Pankowska, MPH, and Cristina Araujo Brinkerhoff, MA (Section of General Internal Medicine, Boston University Chobanian and Avedisian School of Medicine) contributed to qualitative data collection activities. They were all employed by Boston Medical Center at the time of their involvement with the project, and their role on the project was associated with their positions; they were not compensated for their work.

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Advances in Breast Cancer Research

A polyploid giant cancer cell (PGCC) from triple-negative breast cancer.

NCI-funded researchers are working to advance our understanding of how to prevent, detect, and treat breast cancer. They are also looking at how to address disparities and improve quality of life for survivors of the disease.

This page highlights some of what's new in the latest research for breast cancer, including new clinical advances that may soon translate into improved care, NCI-supported programs that are fueling progress, and research findings from recent studies.

Early Detection of Breast Cancer

Breast cancer is one of a few cancers for which an effective screening  test, mammography , is available. MRI ( magnetic resonance imaging ) and  ultrasound  are also used to detect breast cancer, but not as routine screening tools for people with average risk.

Ongoing studies are looking at ways to enhance current breast cancer screening options. Technological advances in imaging are creating new opportunities for improvements in both screening and early detection.

One technology advance is 3-D mammography , also called breast tomosynthesis . This procedure takes images from different angles around the breast and builds them into a 3-D-like image. Although this technology is increasingly available in the clinic, it isn’t known whether it is better than standard 2-D mammography , for detecting cancer at a less advanced stage.

NCI is funding a large-scale randomized breast screening trial, the Tomosynthesis Mammographic Imaging Screening Trial (TMIST) , to compare the number of advanced cancers detected in women screened for 5 years with 3-D mammography with the number detected in women screened with 2-D mammography. 

Two concerns in breast cancer screening, as in all cancer screening, are:

• the potential for diagnosing tumors that would not have become life-threatening ( overdiagnosis )
• the possibility of receiving false-positive test results, and the anxiety that comes with follow-up tests or procedures

As cancer treatment is becoming more individualized, researchers are looking at ways to personalize breast cancer screening. They are studying screening methods that are appropriate for each woman’s level of risk and limit the possibility of overdiagnosis.

For example, the Women Informed to Screen Depending on Measures of Risk (WISDOM) study aims to determine if risk-based screening—that is, screening at intervals that are based on each woman’s risk as determined by her genetic makeup, family history , and other risk factors—is as safe, effective, and accepted as standard annual screening mammography.

WISDOM is also making a focused effort to enroll Black women in the trial. Past studies  tended to contain a majority of White women and therefore, there is less data on how screening can benefit Black women. Researchers are taking a number of steps to include as many Black women as possible in the study while also increasing the diversity of all women enrolled.

Breast Cancer Treatment

The mainstays of breast cancer treatment are surgery , radiation , chemotherapy , hormone therapy , and targeted therapy . But scientists continue to study novel treatments and drugs, along with new combinations of existing treatments.

It is now known that breast cancer can be divided into subtypes based on whether they:

• are hormone receptor (HR) positive which means they express  estrogen and/or progesterone receptors  ( ER , PR )

Shortening Radiation Therapy for Some with Early Breast Cancer

A condensed course was as effective and safe as the standard course for women with higher-risk early-stage breast cancer who had a lumpectomy.

As we learn more about the subtypes of breast cancer and their behavior, we can use this information to guide treatment decisions. For example:

• The NCI-sponsored TAILORx clinical trial. The study, which included patients with ER-positive, lymph node-negative breast cancer, found that a test that looks at the expression of certain genes can predict which women can safely avoid chemotherapy.
• The RxPONDER trial found that the same gene expression test can also be used to determine treatment options in women with more advanced breast cancer. The study found that some postmenopausal women with HR positive, HER-2 negative breast cancer that has spread to several lymph nodes and has a low risk of recurrence do not benefit from chemotherapy when added to their hormone therapy. 
• The OFSET trial is comparing the addition of chemotherapy to usual treatment ( ovarian function suppression plus hormone therapy) to usual treatment alone in treating premenopausal estrogen receptor (ER)-positive/HER2-negative breast cancer patients who are at high risk of their cancer returning. This will help determine whether or not adding chemotherapy helps prevent the cancer from returning.  

Genomic analyses, such as those carried out through  The Cancer Genome Atlas (TCGA) , have provided more insights into the molecular diversity of breast cancer and eventually could help identify even more breast cancer subtypes. That knowledge, in turn, may lead to the development of therapies that target the genetic alterations that drive those cancer subtypes.

HR-Positive Breast Cancer Treatment 

Hormone therapies have been a mainstay of treatment for HR-positive cancer. However, there is a new focus on adding targeted therapies to hormone therapy for advanced or metastatic HR-positive cancers. These treatments could prolong the time until chemotherapy is needed and ideally, extend survival. Approved drugs include:

Drug Combo Effective for Metastatic Breast Cancer in Younger Women

Ribociclib plus hormone therapy were superior to standard chemotherapy combos in a recent trial.

• Palbociclib (Ibrance) ,  ribociclib (Kisqali) , and  everolimus (Afinitor) have all been approved by the FDA for use with hormone therapy for treatment of advanced or metastatic breast cancer. Ribociclib has been shown to increase the survival of patients with metastatic breast cancer . It has also shown to slow the growth of metastatic cancer in younger women when combined with hormone therapy.
• Elacestrant (Orserdu) is approved for HR-positive and HER2-negative breast cancer that has a mutation in the ESR1 gene, and has spread. It is used in postmenopausal women and in men whose cancer has gotten worse after at least one type of hormone therapy.
• Abemaciclib (Verzenio) can be used with or after hormone therapy to treat advanced or metastatic HR-positive, HER2-negative breast cancer. In October 2021, the Food and Drug Administration ( FDA ) approved abemaciclib in combination with hormone therapy to treat some people who have had surgery for early-stage HR-positive, HER2-negative breast cancer.
• Alpelisib (Piqray)  is approved to be used in combination with hormone therapy to treat advanced or metastatic HR-positive, HER2-negative breast cancers that have a mutation in the PIK3CA gene .
• Sacituzumab govitecan-hziy (Trodelvy) is used for HR-positive and HER2-negative breast cancer that has spread or can't be removed with surgery. It is used in those who have received hormone therapy and at least two previous treatments. It has shown to extend the amount of time that the disease doesn't get worse ( progression-free survival ) and also shown to improve overall survival .

HER2-Positive Breast Cancer Treatment 

The FDA has approved a number of targeted therapies to treat HER2-positive breast cancer , including:

• Trastuzumab (Herceptin) has been approved to be used to prevent a relapse in patients with early-stage HER2-positive breast cancer. 
• Pertuzumab (Perjeta) is used to treat metastatic HER2-positive breast cancer, and also both before surgery ( neoadjuvant ) and after surgery ( adjuvant therapy ). 
• Trastuzumab and pertuzumab together can be used in combination with chemotherapy to prevent relapse in people with early-stage HER2-positive breast cancer.  Both are also used together in metastatic disease, where they delay progression and improve overall survival. 
• Trastuzumab deruxtecan (Enhertu) is approved for patients with advanced or metastatic HER2-positive breast cancer who have previously received a HER2-targeted treatment. A 2021 clinical trial showed that the drug lengthened the time that people with metastatic HER2-positive breast cancer lived without their cancer progressing. The trial also showed that it was better at shrinking tumors than another targeted drug, trastuzumab emtansine (Kadcyla).
• Tucatinib (Tukysa) is approved to be used in combination with trastuzumab and capecitabine (Xeloda) for HER2-positive breast cancer that cannot be removed with surgery or is metastatic. Tucatinib is able to cross the blood–brain barrier, which makes it especially useful for HER2-positive metastatic breast cancer, which tends to spread to the brain. 
• Lapatinib (Tykerb)  has been approved for treatment of some patients with HER2-positive advanced or metastatic breast cancer, together with capecitabine or letrozole.
• Neratinib Maleate (Nerlynx) can be used in patients with early-stage HER2-positive breast cancer and can also be used together with capecitabine (Xeloda) in some patients with advanced or metastatic disease.
• Ado-trastuzumab emtansine (Kadcyla) is approved to treat patients with metastatic HER2-positive breast cancer who have previously received trastuzumab and a taxane . It's also used in some patients with early-stage HER2-positive breast cancer who have completed therapy before surgery ( neoadjuvant ) and have residual disease at the time of surgery.

HER2-Low Breast Cancer

 A newly defined subtype, HER2-low, accounts for more than half of all metastatic breast cancers. HER2-low tumors are defined as those whose cells contain lower levels of the HER2 protein on their surface. Such tumors have traditionally been classified as HER2-negative because they did not respond to drugs that target HER2. 

However, in a clinical trial, trastuzumab deruxtecan (Enhertu) improved the survival of patients with HER2-low breast cancer compared with chemotherapy , and the drug is approved for use in such patients. 

Immunotherapy Improves Survival in Triple-Negative Breast Cancer

For patients whose tumors had high PD-L1 levels, pembrolizumab with chemo helped them live longer.

Triple-Negative Breast Cancer Treatment 

Triple-negative breast cancers (TNBC) are the hardest to treat because they lack both hormone receptors and HER2 overexpression , so they do not respond to therapies directed at these targets. Therefore, chemotherapy is the mainstay for treatment of TNBC. However, new treatments are starting to become available. These include:

• Sacituzumab govitecan-hziy (Trodelvy)  is approved to treat patients with TNBC that has spread to other parts of the body . Patients must have received at least two prior therapies before receiving the drug.
• Pembrolizumab (Keytruda)  is an immunotherapy drug that is approved to be used in combination with chemotherapy for patients with locally advanced or metastatic TNBC that has the PD-L1 protein. It may also be used before surgery (called neoadjuvant ) for patients with early-stage TNBC, regardless of their PD-L1 status.
• PARP inhibitors, which include olaparib (Lynparza) and talazoparib (Talzenna) , are approved to treat metastatic HER2-negative or triple-negative breast cancers in patients who have inherited a harmful BRCA gene mutation. Olaparib is also approved for use in certain patients with early-stage HER2-negative or triple-negative breast cancer. 
• Drugs that block the androgen receptors  or prevent androgen production are being tested in a subset of TNBC that express the androgen receptor.

For a complete list of drugs for breast cancer, see Drugs Approved for Breast Cancer .

NCI-Supported Breast Cancer Research Programs

Many NCI-funded researchers working at the NIH campus, as well as across the United States and world, are seeking ways to address breast cancer more effectively. Some research is basic, exploring questions as diverse as the biological underpinnings of cancer and the social factors that affect cancer risk. And some are more clinical, seeking to translate this basic information into improving patient outcomes. The programs listed below are a small sampling of NCI’s research efforts in breast cancer.

TMIST is a randomized breast screening trial that compares two Food and Drug Administration (FDA)-approved types of digital mammography, standard digital mammography (2-D) with a newer technology called tomosynthesis mammography (3-D).

The  Breast Specialized Programs of Research Excellence (Breast SPOREs)  are designed to quickly move basic scientific findings into clinical settings. The Breast SPOREs support the development of new therapies and technologies, and studies to better understand tumor resistance, diagnosis, prognosis, screening, prevention, and treatment of breast cancer.

The NCI Cancer Intervention and Surveillance Modeling Network (CISNET) focuses on using modeling to improve our understanding of how prevention, early detection, screening, and treatment affect breast cancer outcomes.

The Confluence Project , from NCI's Division of Cancer Epidemiology and Genetics (DCEG) , is developing a research resource that includes data from thousands of breast cancer patients and controls of different races and ethnicities. This resource will be used to identify genes that are associated with breast cancer risk, prognosis, subtypes, response to treatment, and second breast cancers. (DCEG conducts other breast cancer research as well.)

The Black Women’s Health Study (BWHS) Breast Cancer Risk Calculator allows health professionals to estimate a woman’s risk of developing invasive breast cancer over the next 5 years. With the NCI-funded effort, researchers developed a tool to estimate the risk of breast cancer in US Black women. The team that developed the tool hopes it will help guide more personalized decisions on when Black women—especially younger women—should begin breast cancer screening. 

The goal of the Breast Cancer Surveillance Consortium (BCSC) , an NCI-funded program launched in 1994, is to enhance the understanding of breast cancer screening practices in the United States and their impact on the breast cancer's stage at diagnosis, survival rates, and mortality.

There are ongoing programs at NCI that support prevention and early detection research in different cancers, including breast cancer. Examples include:

• The  Cancer Biomarkers Research Group , which promotes research in cancer biomarkers and manages the Early Detection Research Network (EDRN) . EDRN is a network of NCI-funded institutions that are collaborating to discover and validate early detection biomarkers. Within the EDRN, the Breast and Gynecologic Cancers Collaborative Group conducts research on breast and ovarian cancers.
• NCI's Division of Cancer Prevention  houses the Breast and Gynecologic Cancer Research Group which conducts and fosters the development of research on the prevention and early detection of  breast and gynecologic cancers.

Breast Cancer Survivorship Research

NCI’s Office of Cancer Survivorship, part of the Division of Cancer Control and Population Sciences (DCCPS), supports research projects throughout the country that study many issues related to breast cancer survivorship. Examples of studies funded include the impact of cancer and its treatment on physical functioning, emotional well-being, cognitive impairment , sleep disturbances, and cardiovascular health. Other studies focus on financial impacts, the effects on caregivers, models of care for survivors, and issues such as racial disparities and communication.

Breast Cancer Clinical Trials

NCI funds and oversees both early- and late-phase clinical trials to develop new treatments and improve patient care. Trials are available for breast cancer prevention , screening , and treatment . 

Breast Cancer Research Results

The following are some of our latest news articles on breast cancer research and study updates:

• Can Some People with Breast Cancer Safely Skip Lymph Node Radiation?
• Study Adds to Debate about Mammography in Older Women
• Pausing Long-Term Breast Cancer Therapy to Become Pregnant Appears to Be Safe
• A Safer, Better Treatment Option for Some Younger Women with Breast Cancer
• Shorter Course of Radiation Is Effective, Safe for Some with Early-Stage Breast Cancer
• Pembrolizumab Improves Survival in Advanced Triple-Negative Breast Cancer

View the full list of Breast Cancer Research Results and Study Updates .

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• Published: 18 May 2024

Disparities in quality of life among patients with breast cancer based on surgical methods: a cross-sectional prospective study

• Yi Wang 1 ,
• Yibo He 1 ,
• Shiyan Wu 1 &
• Shangnao Xie 1  

Scientific Reports volume  14 , Article number:  11364 ( 2024 ) Cite this article

229 Accesses

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• Breast cancer
• Quality of life

To determine the impact of breast conservation on quality of life and identify treatment-related and other demographic factors associated with post-breast cancer treatment quality of life. A prospective study was conducted on 392 women who underwent breast cancer surgery at Hangzhou Cancer Hospital from January 1, 2013, to December 31, 2022. Operable breast cancer patients who had completed all treatments except endocrine therapy were included. Patients with tumor recurrence/metastasis, bilateral or male breast cancer, and other primary malignancies were excluded. After enrollment, patients were asked to complete the BREAST-Q scale, and their pathological and medical records were reviewed. Analysis of variance was used to compare the quality of life scores among the groups. Univariate and multivariate linear regression analyses were performed to identify independent factors associated with quality of life scores in different domains. Participants completed the BREAST-Q scale at a median of 4.6 years after surgery. Quality of life scores varied based on the therapeutic strategy. Breast conservation has significant advantages over mastectomy in terms of breast satisfaction, psychosocial, and sexual well-being. Compared to oncoplastic breast-conserving surgery, mastectomy was independently associated with decreased breast satisfaction, psychosocial, and sexual well-being, while conventional breast-conserving surgery showed comparable outcomes to oncoplastic breast-conserving surgery in terms of these factors. Breast conservation leads to an improvement in quality of life compared to mastectomy. Oncoplastic breast-conserving surgery does not lead to a decrease in quality of life compared to conventional breast-conserving surgery and offers better outcomes compared to mastectomy.

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Introduction.

Breast cancer is a prevalent global malignancy 1 , and breast-conserving surgery (BCS) with adjuvant radiotherapy (RT) is a well-established treatment for early-stage breast cancer 2 , 3 . However, up to 30% of BCS recipients express dissatisfaction with their postoperative appearance, necessitating corrective interventions 4 . In the 1980s, European surgeons introduced "oncoplastic breast-conserving surgery" (OBCS), which incorporates plastic surgery techniques for post-BCS breast defect reconstruction 5 .

While OBCS offers satisfactory long-term oncological results and broadens treatment possibilities for patients who would typically undergo mastectomies 6 , it involves more extensive incisions, additional tissue manipulation, and potential flap reconstruction in comparison to conventional breast-conserving surgery (cBCS) 7 , 8 . The procedures involved in OBCS are more complex, time-consuming, and costly. Given these complexities, is it still worthwhile to pursue breast conservation by OBCS? Some researchers have proposed whether the use of OBCS should be reduced 9 .

Understanding the impact on the quality of life of breast cancer survivors is crucial given its significant influence on medical decision-making 10 , 11 . Despite the widespread utilization of OBCS to conserve the breast and enhance its aesthetics, research on its impact on quality of life is limited and complicated due to the variability of surgical approaches. Consequently, this study aimed to assess the effect of breast conservation by OBCS on the quality of life of patients with operable breast cancer treated at Hangzhou Cancer Hospital from January 1, 2013, to December 31, 2022, and to elucidate the treatment and demographic factors associated with postoperative quality of life.

Materials and methods

This prospective, cross-sectional, case–control study was conducted at a single center. The inclusion criteria were operable breast cancer patients treated at Hangzhou Cancer Hospital between January 1, 2013, and December 31, 2022, who had completed all treatments except endocrine therapy and provided participation consent. The exclusion criteria were patients with tumor recurrence/metastasis, bilateral or male breast cancer, or other primary malignancies. Participants were categorized into two groups: BCS group (cBCS with RT subgroup and OBCS with RT subgroup), and unilateral MAST group (MAST with RT subgroup and MAST without RT subgroup). This study utilized the BREAST-Q scale 12 , which includes separate modules for BCS and MAST without reconstruction. The BCS module was used for the OBCS with RT subgroup because OBCS in this study predominantly referred to oncoplastic lumpectomy/glandular remodeling. BREAST-Q assesses six distinct domains: satisfaction with breasts, psychosocial well-being, physical well-being, sexual well-being, satisfaction with overall outcome, and satisfaction with care. Due to the elapsed time between surgery and questionnaire completion in this study, the domains of satisfaction with the overall outcome and satisfaction with care were excluded. Each domain was scored on a scale from 0 to 100, with higher scores indicating an enhanced quality of life. Differences in BREAST-Q scores were categorized as small (2–3 points), moderate (4–7 points), and large (8–10 points) 13 . Patient characteristics, collected using the questionnaire, included employment status, educational level, marital status, and economic status. Patients’ medical and pathological records were reviewed to determine the disease tumor, node, and metastasis (TNM) staging 14 , erythroblastic oncogene B (ERBB2; formerly HER2/neu or HER2) status, hormone receptor status, and body mass index (BMI). Information on surgery, chemotherapy (yes/no), RT, and endocrine therapy (yes/no) was obtained using a questionnaire in conjunction with medical records. The lymphedema status (yes/no) was assessed using the questionnaire's question regarding arm swelling. This study was approved by the Ethics Committee of Hangzhou Cancer Hospital, and all participants provided written informed consent. The study was performed in accordance with the Declaration of Helsinki and followed the guidelines of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) reporting guidelines.

Statistical analysis

The experimental data were statistically analyzed using SPSS (version 29.0) software, and categorical covariates were expressed as numbers (percentages). Analysis of variance (ANOVA) was used to compare quality of life scores among the different groups. Univariate and multivariate linear regression analyses were used to determine the independent factors associated with the quality of life scores in each domain. Variables with two-tailed P  ≤ 0.15 in the univariate analysis were included in the multivariate analysis model using a stepwise method to establish the final multivariate model. Differences with P  < 0.05 were considered statistically significant.

Ethics approval and consent to participate

This study was reviewed and approved by the ethics committee of Hangzhou Cancer Hospital (approval number: [hzch-2023] HS no.007). Written informed consent was obtained from every patient.

Patient enrollment

After screening, 623 eligible patients were invited, 456 provided written informed consent and completed the survey, but three were found to not meet the inclusion criteria after enrollment. After excluding 61 participants who only completed a brief questionnaire, a total of 392 patients’ data were included in the statistical analysis.

Patient, disease, and treatment characteristics

The interval between surgery and scale completion averaged 4.6 years (range: 0.33 to 9.83 years). Patient characteristics are detailed in Table 1 . Majority were married, employed, had moderate economic status (income ¥30,000–200,000 per year), and high school or higher education. At surgery, 324 (82.7%) patients had a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) within the normal range (18.5 to 23.9 kg/m 2 ), and 56 (14.3%) patients had a BMI of 24 kg/m 2 or above. Among the patients, 39 (9.9%) had stage 0 breast cancer, 154 (39.3%) had stage I breast cancer, 158 (40.3%) had stage II breast cancer, and 41 (10.5%) had stage III breast cancer. The lesions on imaging before surgery of 253 (64.5%) patients measured two centimeters or less, 134 (34.2%) two to five centimeters, and 5 (1.3%) more than five centimeters. Chemotherapy was administered to 293 (74.7%) patients, with 121(30.9%) receiving neoadjuvant chemotherapy, and 273 (69.6%) patients received hormone therapy.

Treatment details including surgery, RT, and lymphedema are presented in Table 1 . Among the patients, 88 (22.4%) underwent OBCS, 51 (13.0%) underwent cBCS, and 253 (64.5%) underwent unilateral MAST, among which 100 (25.5%) patients who underwent unilateral MAST received postoperative RT. All patients underwent axillary surgery, with 255 (65.1%) patients undergoing sentinel lymph node biopsy only and 137 (34.9%) patients undergoing axillary lymph node dissection. 61 (15.6%) patients reported having lymphedema.

BREAST-Q results by breast surgery strategy

Figure  1 illustrates unadjusted mean BREAST-Q scores by breast surgery strategy. Satisfaction with breasts, psychosocial well-being and sexual well-being were significantly different among the groups ( P  < 0.001). BCS group showed higher scores in satisfaction with breasts (61.70), psychosocial well-being (76.01), physical well-being (83.52) and sexual well-being (55.06), while the scores for MAST group is lower (satisfaction with breasts: 57.30, psychosocial well-being: 70.83, physical well-being: 82.40 and sexual well-being: 49.21).

Unadjusted BREAST-Q mean scores by breast surgery strategy. BCS: breast-conserving surgery; MAST: mastectomy.

Satisfaction with breasts

Higher scores in satisfaction with breasts correlated independently with age ≥ 60 (β = 4.662; 95% CI = 2.345 to 6.979; P  < 0.001) and patient-reported income ≥ 200,000 (β = 5.068; 95% CI = 2.781 to 7.356; P  < 0.001). Lower scores were associated with BMI ≥ 24 (β = − 2.528; 95% CI = − 4.977 to − 0.079; P  = 0.043), axillary dissection (β = − 4.875; 95% CI = − 6.704 to − 3.046; P  < 0.001) and MAST (β = − 3.927; 95% CI = − 5.741 to − 2.113; P  < 0.001) (Fig.  2 A). Patient-reported income < 30,000 and lymphedema showed significance only in univariate analysis. Other factors exhibited no significant association.

Patient and treatment factors associated with breast satisfaction ( A ), psychosocial well-being ( B ), physical well-being ( C ) and sexual well-being ( D ) scores by breast surgery strategy. MAST: mastectomy; BCS: breast-conserving surgery; BMI: body mass index; CI: confidence interval.

Psychosocial well-being

Better psychosocial well-being correlated with age ≥ 60 (β = 2.564; 95% CI = 0.163 to 4.965; P  = 0.036), patient-reported income ≥ 200,000 (β = 4.820; 95% CI = 2.496 to 7.144; P  < 0.001), and ≥ 5y from surgery (β = 2.419; 95% CI = 0.523 to 4.315; P  = 0.013). Poor psychosocial well-being was linked to age < 35 (β = − 3.892; 95% CI = − 7.715 to − 0.069; P  = 0.046), BMI ≥ 24 (β = − 3.352; 95% CI = − 5.845 to − 0.859; P  = 0.009), patient-reported income < 30,000 (β = − 4.489; 95% CI = − 7.317 to − 1.660; P  = 0.002), axillary dissection (β = − 5.898; 95% CI = − 7.739 to − 4.058; P  < 0.001) and MAST (β = − 5.157; 95% CI = − 7.032 to − 3.283; P  < 0.001) (Fig.  2 B). Chemotherapy was only significant in univariate analysis. Other variables showed no significant association.

Physical well-being

Factors associated with better physical well-being were age ≥ 60 (β = 3.594; 95% CI = 1.554 to 5.634; P  = 0.001), patient-reported income ≥ 200,000 (β = 4.541; 95% CI = 2.559 to 6.524; P  < 0.001), and ≥ 5y from surgery (β = 2.311; 95% CI = 0.714 to 3.907; P  = 0.005). Conversely, patient-reported income < 30,000 (β = − 5.924; 95% CI = − 8.351 to − 3.497; P  < 0.001), axillary dissection (β = − 2.486; 95% CI = − 4.057 to − 0.914; P  = 0.002) and lymphedema (β = − 2.185; 95% CI = − 4.275 to − 0.094; P  = 0.041) were associated with poorer physical well-being (Fig.  2 C). < 1y from surgery was only significant in univariate analysis. Other factors lacked significant association.

Sexual well-being

Multivariate analysis indicated lower sexual well-being scores with BMI ≥ 24 (β = − 2.887; 95% CI = − 4.831 to − 0.943; P  = 0.004), < 1y from surgery (β = − 3.482; 95% CI = − 5.887 to − 1.077; P  = 0.005), axillary dissection (β = − 3.002; 95% CI = − 4.437 to − 1.567; P  < 0.001), and MAST (β = − 5.650; 95% CI = − 7.114 to − 4.187; P  < 0.001). Patient-reported income ≥ 200,000 (β = 2.272; 95% CI = 0.441 to 4.104; P  = 0.015) correlated with elevated sexual well-being (Fig.  2 D). Lymphedema was significant in univariate analysis. Other variables exhibited no significant correlation.

BREAST-Q results by local therapy strategy

To assess if there were enhancements in quality of life among women who underwent OBCS, we performed similar analyses among the subgroups. Figure  3 illustrates unadjusted mean BREAST-Q scores by local therapy strategy. All four domains were significantly different ( P  < 0.05). OBCS with RT group showed highest scores in satisfaction with breasts (61.99), psychosocial well-being (76.27) and sexual well-being (55.53). cBCS with RT group yielded the highest physical well-being score (84.10). The lowest domain scores were in MAST with RT group (satisfaction with breasts: 53.11, psychosocial well-being: 65.49, physical well-being: 79.89 and sexual well-being: 46.24).

Unadjusted BREAST-Q mean scores by local therapy strategy. RT: radiotherapy; cBCS: conventional breast-conserving surgery; OBCS: oncoplastic breast-conserving surgery; MAST: mastectomy.

Multivariate analysis indicated that MAST with RT was associated with poor breast satisfaction (β = − 8.381; 95% CI = − 10.858 to − 5.905; P  < 0.001), psychosocial well-being (β = − 11.491; 95% CI = − 14.039 to − 8.943; P  < 0.001), physical well-being (β = − 3.607; 95% CI = − 5.782 to − 1.432; P  = 0.001) and sexual well-being (β = − 9.493; 95% CI = − 11.454 to − 7.533; P  < 0.001). MAST without RT was associated with decreased breast satisfaction (β = − 2.536; 95% CI = − 4.817 to − 0.255; P  = 0.029), psychosocial well-being (β = − 3.171; 95% CI = − 5.487 to − 0.855; P  = 0.007) and sexual well-being (β = − 4.739; 95% CI = − 6.530 to − 2.947; P  < 0.001). cBCS with RT was not associated with BREAST-Q scores on univariate or multivariate analysis. The statistically significant factors correlated with BREAST-Q scores were mostly consistent with the outcomes of the breast surgery models (Fig.  4 ).

Patient and treatment factors associated with breast satisfaction ( A ), psychosocial well-being ( B ), physical well-being ( C ) and sexual well-being ( D ) scores by local therapy strategy. cBCS: conventional breast-conserving surgery; OBCS: oncoplastic breast-conserving surgery; MAST: mastectomy; RT: radiotherapy; BMI: body mass index; CI: confidence interval.

The rates of BCS and breast reconstruction after mastectomy are significantly lower in China than in Western countries 15 . One contributing factor is that Chinese women typically have smaller breast sizes than women in Western countries, while presenting with larger breast tumor volumes at the time of initial diagnosis, making BCS challenging. Additionally, some Chinese patients adhere to outdated beliefs and have concerns about potential impacts on treatment outcomes or cancer recurrence associated with BCS. OBCS provides acceptable long-term oncological outcomes and has extended treatment options for patients who would traditionally be candidates for mastectomies 6 . In recent years, there has been a clear change in the emphasis of surgical oncology in China, with a growing emphasis on utilizing modern oncoplastic surgical techniques to perform more breast conserving surgeries. Given the increasing prevalence of OBCS, it is essential to examine its impact on quality of life.

In this single-center prospective study, discernible disparities in quality of life surfaced among patients with breast cancer undergoing various local treatment strategies within ten years of surgery. Patients opting for more extensive surgery, particularly when combined with RT, experienced diminished quality of life; satisfaction with breasts; and psychosocial, physical, and sexual well-being. This aligns with findings from prior studies. Engel et al.’s study 16 has shown that patients undergoing BCS reports a higher quality of life compared to those opting for mastectomy. This improvement is often linked to the conservation of the breast and the associated psychological advantages. BCS enables breast conservation, leading to enhanced body image and self-esteem. Patients undergoing BCS may experience less psychological distress and enjoy better psychosocial well-being due to breast conservation. Additionally, BCS has a lesser impact on sexual well-being in comparison to mastectomy, as it retains natural breast tissue.

This study’s findings concur with those of Otsuka et al.’s study 17 in that oncoplastic surgery improved satisfaction with breasts. However, in Otsuka et al.’s study, the quality of life score was not elevated by OBCS (major breast surgery: 154.5 ± 24.6; minor breast surgery: 159.0 ± 20.8; OBCS: 158.7 ± 14.0). Although differences exist between major breast surgery and OBCS, the difference is not pronounced. In the present study, psychosocial and sexual well-being scores were elevated compared to MAST. Additionally, patients who underwent OBCS had better physical well-being scores than those who underwent MAST with RT and equal physical well-being scores than those who underwent MAST without RT. This may be attributable to the omission of RT, reduced chemotherapy and lymphedema in the MAST without RT group. Previous studies 18 , 19 have highlighted RT, chemotherapy, and lymphedema as adverse determinants of quality of life.

Rose et al. 20 suggested that patients who underwent OBCS showed significant improvement in the “psychosocial well-being” module compared to cBCS, while no significant differences were observed between the two groups in the “physical health,” “breast satisfaction,” and “sexual health” modules. Furthermore, a meta-analysis 21 indicated improved quality of life with OBCS compared with cBCS in patients with early-stage breast cancer, with better physical and psychological well-being, higher self-esteem, and a more stable body image, leading to improved social and emotional functioning. However, the clinical studies included in the meta-analysis were predominantly small- sample studies from single centers, and the surgical approaches varied. This study identified no significant differences in any of the quality of life modules between the patients who underwent OBCS and those who underwent cBCS, which is consistent with the findings of de Oliveira-Junior et al 22 . This may be because the present study’s follow-up time was longer, and several aspects of OBCS will decline over time 23 . In our study, the tumor lesion on imaging before surgery averaged 2.11 ± 0.67 cm in OBCS subgroup, and 1.62 ± 0.52 cm in cBCS subgroup. Smaller lesions are more likely to undergo cBCS, resulting in comparable cosmetic outcomes between the two surgical groups. Moreover, the limited number of BCS patients in our study is a significant factor that limits the ability to detect differences in quality of life between OBCS and cBCS subgroups.

In addition to the type of surgery, other clinical factors such as BMI (≥ 24), income (< 30,000), < 1y from surgery, axillary dissection, and lymphedema were negatively correlated with quality of life. Identifying these risk factors can facilitate early postoperative intervention and ultimately improve the postoperative quality of life of patients with breast cancer. Age (≥ 60) and ≥ 5y from surgery were associated with enhanced quality of life. Breast cancer patients can experience significant effects from the disease itself and the ongoing adjuvant therapies, both after diagnosis and during the treatment process 24 . These are all factors that lead to decreased quality of life within 5 years, especially within 1 year, rather than ≥ 5y after surgery. Moreover, good economic status was associated with better satisfaction with breasts, and psychosocial, physical, and sexual well-being. Patients with improved financial circumstances can access higher-quality healthcare services, opt for more expensive treatment options that may improve aesthetic outcomes. The financial advantage also affords patients more opportunities for supportive care, counseling, and resources to manage the challenges of breast cancer treatment and recovery, resulting in a decrease in stress, anxiety, and depression. These enhancements can have a positive impact on patients’ self-perception, confidence, and overall satisfaction with their breast appearance, all of which are closely connected to sexual health and intimacy. Notably, other studies 25 , 26 found an association between economic status and quality of life.

This study has some limitations. It was a cross-sectional, single-time, survey-based prospective study; therefore, the baseline quality of life of patients before surgery was not recorded, which may have influenced their choice of surgical approach and postoperative quality of life. Additionally, this study did not identify patients who chose MAST due to refusal of BCS; patients who selected MAST based on personal preferences may have different quality-of-life scores. Furthermore, this study did not include patients with postmastectomy breast reconstructions, which may improve quality of life of postmastectomy patients. Finally, given that this was a single-center small-sample study, studies with larger sample sizes are required to further confirm the findings of this study. Nevertheless, patient-reported questionnaires can provide basic information on quality of life and assist in identifying potential areas requiring intervention during the patient’s survival period.

OBCS is an acceptable option for patients with larger tumors who are not suitable for cBCS because it allows them to conserve their breasts 6 . This study demonstrated that patients who had their breast conserved reported a higher quality of life compared to mastectomy patients. Despite extensive incisions, additional tissue manipulation, and potential flap reconstruction, patients who underwent OBCS did not report a lower quality of life than those who underwent cBCS. Furthermore, they experienced significantly enhanced quality of life compared with patients who underwent MAST, particularly in the domains of satisfaction with breasts, psychosocial well-being, and sexual well-being. Quality of life data should be incorporated into decision support tools to assist patients with breast cancer in selecting the surgical approach, and discussions with patients should include information regarding quality of life to ensure that they understand the long-term impacts of different surgical approaches. This is particularly crucial because most patients with breast cancer have an extended postoperative survival period. Our data can support further improvements in Chinese breast surgical care for better survival and quality of life.

Data availability

The datasets generated and/or analyzed during the current study are not publicly available due to Chinese law but are available from the corresponding author on reasonable request.

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The interpretation and reporting of these data are the sole responsibility of the authors, and no endorsement by the Hangzhou Cancer Hospital is intended nor should be inferred.

This research was financed by the Medical and Health Research Project of Zhejiang Province, China (No. 2023KY964).

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Yi Wang, Yibo He, Shiyan Wu & Shangnao Xie

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YW and SX contributed to the conception, design, wrote the manuscript and analyzed the data; YH was responsible for the execution and for data collection; and SW supervised the study. All authors read and approved the final manuscript.

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Wang, Y., He, Y., Wu, S. et al. Disparities in quality of life among patients with breast cancer based on surgical methods: a cross-sectional prospective study. Sci Rep 14 , 11364 (2024). https://doi.org/10.1038/s41598-024-62105-z

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DOI : https://doi.org/10.1038/s41598-024-62105-z

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Top 100 Cited Classic Articles in Breast Cancer Research

This study aimed to analyze 100 most cited articles in breast cancer research.

Materials and Methods

The data in this study were obtained by a search conducted on the Web of Science (WOS). In brief, the term “breast cancer” was typed in the search box of WOS basic research including all the years and the data. The analysis was carried out by compiling the top 100 cited articles in the shortlist as sorted by the journals, categories of the studies, the countries, the centers, the authors and the publication date. No statistical methods were used in the study. All data were reported as percentages, numbers and bar charts on tables.

Our findings showed that the most frequently cited article received 7609 citations to date. Most articles were published in the New England Journal of Medicine. 81% of the studies originated from the USA. The National Institutes of Health (NIH USA) was ranked the first with 21% and it was followed by Harvard University in terms of number of published articles. 42% of the articles were published under the category of medicine and general internal medicine.

Top 100 most cited articles originated from the United States. The highest number of articles among the top 100 articles were published in New England Journal of Medicine and National Institutes of Health NIH USA was the leading institutes published the most articles.

Introduction

There has been a growing increase in the incidence of breast cancer ( 1 ), which is still the most significant cancer-related cause of female mortality ( 2 ). In spite of significant progress in the management of breast cancer, the search for a curative treatment is still ongoing. Although a number of crucial studies and clinical trials have significantly contributed to the improvement of breast cancer care, many often remain unknown to the majority of clinicians, suggesting a need to identify at least the top 100 most cited studies in the field. Actually, in the past, there were a couple of studies which identified the most cited articles in several fields such as digestive disease and psychology ( 3 , 4 ), which helped the researchers in this field to easily access them. This identification is important because the decisions made by the clinicians are generally based on the evidence and the studies with a high impact ( 5 ). The most significant component of the methodological qualities of studies is associated with an increase of citation and a high impact factor of the journal where it is published ( 6 ). The object of this study was to identify and analyze the qualities of the top 100 cited papers in breast cancer-related studies.

The data in this study were obtained by a search conducted on the Web of Science (WOS) (Clarivate Analytics, United States). The journals indexed in the Science Citation Index Expanded were included. There were no restrictions on the journals. The Science Citation Index Expanded in WOS covers more than 8,500 notable and major journals encompassing 150 disciplines. The coverage time extends from 1900 to the present ( 7 ). The term “Breast cancer” was typed into the search box of WOS basic research with the selection of all the years and the data were searched in Title setting. Our search produced 189.235 published articles between 1978–2017. Thereafter, they were listed based on the citation frequency-from the highest to the lowest. The analysis was carried out by compiling the Top 100 cited classical articles in a shortlist as sorted by the journals, categories of the studies, countries, centers where the studies were published, authors and publication date. Since this was not invasive study, an approval from the ethical committee was not requested. The study was conducted in accordance with the Declaration of Helsinki.

Statistical analysis

No statistical methods were used in the study. All the data were given in percentages, numbers and bar charts.

The articles included in the study were ranked according to the frequency of citation ( Table 1 ). Our search demonstrated that among the top 100 articles, the most frequently cited article received 7609 citations while the least cited article received 960 citations. We found that 93 of the articles received more than 1000 citations and determined that the top 100 articles were published between 1985 and 2011 ( Table 2 ). The number of most cited articles peaked in 2005 with 12 publications, while the number of least cited in articles peaked in 1990 and 1993 with only two publications.

The top 100 cited articles in breast cancer research

Distribution of articles by publication date

These top 100 articles were published in 14 high-impact journals where 25 out of 100 articles were published in the New England Journal of Medicine ( Table 3 ).

Journals in which the top 100 cited articles were published

81% of the studies originated from the USA while the rest originated from the UK, Canada and Italy ( Table 4 ). These top 100 articles that originated from 50 different centers and National Institutes of Health (NIH USA) ranked as the first with 21% of total articles followed by Harvard University and NIH National Cancer Institute (NCI). The University of Washington ranked the last with 4% ( Table 5 ).

Countries of origin of the top 100 cited article

Institutions of origin

Among top 100 authors in these articles, Wolmark N. was determined to be the mostly cited common author with 12% followed by Fisher B. and Bryant J., respectively ( Table 6 ). Furthermore, 42% of these articles were categorized under the title of medicine and general internal medicine followed by studies under the category of multidisciplinary sciences, oncology and genetic hereditary diseases, respectively. The rate of studies under the surgery category was found to be the lowest with 2% ( Table 7 ).

Most common the first 20 authors

Discussion and Conclusion

Bibliometric analysis can be conducted in many areas for different purposes ( 8 , 9 ) and can be used to reveal the historical development in a field ( 9 ). In this study, we aimed to identify the top 100 most cited articles in breast cancer research to help researchers easily access and analyze them. In that respect, this study is one of the early studies under the title of breast cancer.

Although analyzing the top 100 most cited articles was relatively difficult, we identified that the top 100 articles were published between 1985 and 2011 thanks to systems such as WOS. The citations mostly peaked between 2005 and 2007. The number of citations to the studies conducted in the areas of orthopedics and neurosurgery peaked between 1965 and 1980 ( 10 , 11 ). However, the citation frequency of studies in the field of cardiology peaked between 2001 and 2010 ( 12 ). This result may suggest that the development and progression in the area of breast cancer may have occurred within a short period of time. In parallel with the technological advances that have occurred in the last two decades, a significant progress in breast cancer research has been also achieved.

The number of citations is closely associated with the publishing date, and has been increasing with time ( 9 ). For this reason, the vast majority of articles with a high number of citations consisted of early-published articles. No papers published after 2011 appeared in our list. However, the number of citations is not solely depended on publication date. For example, one article in our list published in 2005 received more citations than other articles published between 1985 and 1995.

Another interesting point of our analysis is that all the articles were published in journals with a high impact factor. The New England Journal of Medicine, Lancet and Science were the journals which mostly published top 100 articles, indicating that the vast majority of the studies were published in the best-known general medical journals rather than specific journals in this field. It may be speculated that the audience of a general medical journal may be closely interested in the issue of breast cancer or it is possible to consider that the authors of studies on breast cancer preferentially choose the journals with a high impact.

Another point of our study is that the top 100 articles most often originated from the United States. The bibliometric analyses in other areas also showed that the United States ranked high on the list ( 13 , 14 ). These findings clearly show that the United States is at the forefront of studies on breast cancer. A wide range of patient population and a substantial amount of financial support to researchers can be the main reason behint this.

The authors who have received the highest number of citations are the people who are prominent in their field. For example, Wolmark N. authored 12 articles in the top 100 articles whereas Slamon Dennis J. was not in the list of the first 20 authors who have the highest number of articles although he was the first author in the first 3 articles that received the highest number of citations.

Breast cancer research has progressed historically and gone through milestones in various areas in this process. These areas include breast cancer gene associations, breast cancer treatment modalities, hormonal therapies, HER2 and breast cancer involvement, sentinel lymphadenectomy, breast conserving surgery, breast cancer metastasis, survival, neoadjuvant chemotherapy and breast screening.

Slamon Dennis J. was observed as the first author in first 3 articles with the highest number of citations. All three articles were about the oncogene HER2 / neu. It has been emphasized that HER2 / neu amplification gene has a high prognostic value and this gene may play a role in the pathogenesis of breast cancer. The first three articles with the highest number of citations are very important in terms of revealing the correlation between HER2 / neu and breast cancer. Prognosis is very low in patients with HER2 / neu positive breast cancer. For this reason, HER2-targeting therapies are thought to have positive effects on outcomes. Romond, Edward H., et al. showed an improvement in the outcomes of women with HER2-positive breast cancer treated with trastuzumab, a monoclonal antibody targeting the extracellular domain of HER2. Piccart-Gebhart, Martine J. et al also demonstrated the efficacy of trastuzumab in HER2-positive breast cancer patients after adjuvant chemotherapy. Vogel, Charles L., et al., showed that trastuzumab is safe and effective as a single agent in the first-line treatment of HER2-positive metastatic breast cancer patients. Seven of the top 100 articles are related to HER2 and trastuzumab and they are an important milestone in this field.

Today, hormonal treatments in breast cancer have an important place in therapy. Remmele, W., and H.E. Stegner identified estrogen receptors immunohistochemically from breast cancer tissues in 1987. Fisher, Bernard, et al. published a paper in 1989, showing a randomized clinical trial which demonstrated the efficacy of tamoxifen on breast cancer in patients that are estrogen- and progesterone-receptor-positive. This study provided significant progress in breast cancer treatment. The Early Breast Cancer Trialists’ Collaborative Group investigated the efficacy of tamoxifen in early breast cancers in 1998. Fisher, Bernard et al. explained the protective effects of tamoxifen on breast cancer in 1998.

Gene-based studies have been conducted on breast cancer through the demonstration of the effects of genetic factors in many types of cancer. Miki Y, Swensen J, et al. reported the association of the BRCA-1 gene with breast cancer and ovarian cancer in 1994. Wooster, Richard, et al, showed a relationship between BRCA-2 gene and breast cancer in 1995. Easton, Douglas F. et al. investigated the incidence of breast and over-cancer in BRCA-1 gene mutation carriers. Ford, Deborah et al. showed that families with breast cancer have BRCA-1 and BRCA-2 identified in their gene analysis in relation to breast cancer in 1998. Antoniou, Anthony et al. published a study entitled ‘’ “Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies” in 2003. Today, BRCA1 and 2 genes can be examined and prophylactic mastectomy can be decided upon ( Table 1 ).

Veronesi, Umberto et al. showed that using sentinel-node biopsy can help avoid axillary dissection in breast cancer patients with clinical negative lymph-nodes. Krag, David et al. emphasized the importance of sentinel node in breast cancer. In another study by Krag, D. N., et al., they showed that sentinel-node can be found by radiocalization with gamma probe. In 1994, Giuliano, Armando E. et al. described sentinel lymphadenectomy by lymphatic mapping. In 2003, Veronesi, Umberto et al. published a paper entitled “A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer”, and stated that sentinel-node biopsy was a safe and reliable method. All these papers constituted the milestones for avoiding unnecessary axillary dissection in breast cancer patients, and helped reduce morbidity associated with breast surgery ( Table 1 ).

While radical mastectomy surgery was commonly used as the conventional breast cancer treatment, modified radical mastectomy and especially preventive breast surgery are generally chosen as a curative treatment at the present time. The reason behind this change in treatment method actually is rooted in the findings of the following milestone papers: in 1981, the paper published by Veronesi, Umberto et al. compared radical mastectomy to quadrantectomy, and they found that there were no differences between these groups in terms of disease-free or overall survival rate. Fisher, Bernard et al. published a paper in 1985 entitled “Five-year results of a randomized clinical trial comparing total mastectomy and segmental mastectomy with or without radiation in the treatment of breast cancer.” and they determined that segmental mastectomy with breast irradiation and adjuvant chemotherapy was the appropriate treatment method in stage I and II breast cancer (less than 4 cm).

The rest of the top 100 cited articles were associated with adjuvant and neoadjuvant treatments, survival, breast cancer metastasis, and breast screening. These studies contribute to breast research by providing significant improvements.

In this bibliometric analysis, the vast majority of the top 100 articles were in the category of general internal medicine. It was followed by multi-disciplinary sciences, and the third in rank was oncology research. Surgery was at the bottom of the list. However, surgeons have significantly contributed to the area of breast cancer. The effects of significant studies which have been conducted in recent years will be seen during the upcoming years.

There are some limitations to our study. Only the studies having breast cancer in their title were included in the study. However, breast cancer as the topic of the studies was not taken into consideration. The studies on the topic of breast cancer with a high number of citations can also be separately analyzed. The results which have been found by typing ‘breast, breast neoplasm’ in the search box of WOS can be separately added to the analysis. In order to ensure homogenization in our study, analyses have been conducted under only one title and search.

As a result, it was found that top 100 most cited publications predominantly originated from the United States. The largest part of top 100 articles was published in New England Journal of Medicine. Most articles were published under the category of general internal medicine. The highest number of publications was in 2005. The articles about HER2 / neu were listed as the first three articles. It was determined that National Institutes of Health NIH USA and Harvard University were the institutes which published the highest number of articles.

Analysis of highly cited articles with ‘breast cancer’ in their title provided the opportunity to recognize the progress made in studies on breast cancer. It also provides a historical perspective on the development of breast cancer studies.

Ethics Committee Approval: Ethics committee approval was not requested for this study.

Informed Consent: Informed consent is not necessary as our work is a retrospective international data study.

Peer-review: Externally peer-reviewed.

Author Contributions: Concept - EU.; Design - EU.; Supervision - EU.; Resources - EU.; Materials - EU.; Data Collection and/or Processing - EU.; Analysis and/or Interpretation - EU.; Literature Search - EU.; Writing Manuscript - EU.; Critical Review - EU.; Other - EU.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

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• Risk Factors
• Breast Cancer Resources to Share
• What CDC Is Doing About Breast Cancer
• Advisory Committee on Breast Cancer in Young Women
• MMWR Appendix
• National Breast and Cervical Cancer Early Detection Program
• Bring Your Brave Campaign

Breast Cancer Risk Factors

• Your risk for breast cancer is due to a combination of factors.
• The main factors that influence your risk include being a woman and getting older.

Studies have shown that your risk for breast cancer is due to a combination of factors. The main factors that influence your risk include being a woman and getting older. Most breast cancers are found in women who are 50 years old or older.

Some women will get breast cancer even without any other risk factors that they know of. Having a risk factor does not mean you will get the disease, and not all risk factors have the same effect. Most women have some risk factors, but most women do not get breast cancer. Talk with your doctor about ways you can lower your risk and about screening for breast cancer.

Risk factors you cannot change

• Getting older. The risk for breast cancer increases with age. Most breast cancers are diagnosed after age 50.
• Genetic mutations. Women who have inherited changes (mutations) to certain genes, such as BRCA1 and BRCA2, are at higher risk of breast and ovarian cancer.
• Reproductive history. Starting menstrual periods before age 12 and starting menopause after age 55 expose women to hormones longer, raising their risk of getting breast cancer.
• Having dense breasts. Dense breasts have more connective tissue than fatty tissue, which can sometimes make it hard to see tumors on a mammogram. Women with dense breasts are more likely to get breast cancer.
• Personal history of breast cancer or certain noncancerous breast diseases. Women who have had breast cancer are more likely to get breast cancer a second time. Some noncancerous breast diseases such as atypical ductal hyperplasia or lobular carcinoma in situ are associated with a higher risk of getting breast cancer.
• Family history of breast or ovarian cancer. A woman's risk for breast cancer is higher if she has a mother, sister, or daughter (first-degree relative) or multiple family members on either her mother's or father's side of the family who have had breast or ovarian cancer. Having a first-degree male relative with breast cancer also raises a woman's risk.
• Previous treatment using radiation therapy. Women who had radiation therapy to the chest or breasts (for instance, treatment of Hodgkin's lymphoma) before age 30 have a higher risk of getting breast cancer later in life.
• Exposure to the drug diethylstilbestrol (DES). DES was given to some pregnant women in the United States between 1940 and 1971 to prevent miscarriage. Women who took DES have a higher risk of getting breast cancer. Women whose mothers took DES while pregnant with them also may have a higher risk of getting breast cancer.

Risk factors you can change

• Not being physically active. Women who are not physically active have a higher risk of getting breast cancer.
• Being overweight or having obesity after menopause. Older women who are overweight or have obesity have a higher risk of getting breast cancer than those at a healthy weight.
• Taking hormones. Some forms of hormone replacement therapy (those that include both estrogen and progesterone) taken during menopause can raise risk for breast cancer when taken for more than 5 years. Certain oral contraceptives (birth control pills) also have been found to raise breast cancer risk.
• Reproductive history. Having the first pregnancy after age 30, not breastfeeding, and never having a full-term pregnancy can raise breast cancer risk.
• Drinking alcohol. Studies show that a woman's risk for breast cancer increases with the more alcohol she drinks.

Research suggests that other factors such as smoking, being exposed to chemicals that can cause cancer, and changes in other hormones due to night shift working also may increase breast cancer risk.

What Would You Tell Your Patients About Drinking Alcohol and Breast Cancer Risk?

CDC's Dr. Lisa Richardson explains the link between drinking alcoholic beverages and breast cancer risk in this video.

Who is at high risk for breast cancer?

If you have a strong family history of breast cancer or inherited changes in your BRCA1 and BRCA2 genes, you may have a high risk of getting breast cancer. You may also have a high risk for ovarian cancer.

Talk to your doctor about ways to reduce your risk, such as medicines that block or decrease estrogen in your body, or surgery.

"Having a family history increases cancer risk in both genders."‎

Breast cancer.

Talk to your doctor about when to start and how often to get a mammogram.

For Everyone

Public health.