Awareness and Current Knowledge of Breast Cancer PDF

Akram et al.
Biol Res (2017) 50:33

DOI 10.1186/s40659-017-0140-9 Biological Research
REVIEW Open Access
Awareness and current knowledge

of breast cancer
Muhammad Akram1*, Mehwish Iqbal2, Muhammad Daniyal2 and Asmat Ullah Khan3,4
Abstract
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.
Keywords: Breast cancer, Chemotherapy, Gene therapy, Stem cell therapy
Background American female is 12.38% [3]. The significant decline in

Breast cancer is the most common cancer and also morality due to breast cancer in the United States from
the primary cause of mortality due to cancer in female 1975 to 2000 is attributed to constant enhancement in
around the World. About 1.38 million new breast can- both screening mammography and management [4].
cer cases were diagnosed in 2008 with almost 50% of all According to the World Health Organization (WHO),
breast cancer patients and approximately 60% of deaths enhancing breast cancer outcome and survival by early
occurring in developing countries. There is a huge differ- detection remains the foundation of breast cancer regu-
ence in breast cancer survival rates worldwide, with an lations. Different modern medicines are prescribed to
estimated 5-year survival of 80% in developed countries treat breast cancer. Medical therapy of breast cancer with
to below 40% for developing countries [1]. Developing antiestrogens such as raloxifene or tamoxifen might avoid
countries face resource and infrastructure constraints breast cancer in individuals who are at increased possi-
that challenge the objective of improving breast cancer bility of developing it [5]. Surgery of both breasts is an
outcomes by timely recognition, diagnosis and manage- added preventative measure in some increased probabil-
ment [2]. In developed countries like the United States, ity of developing cancer in female. In patients who have
about 232,340 female will be diagnosed and death of been identified with breast tumor, different strategies of
39,620 female will occur due to breast cancer in 2013 management are used such as targeted therapy, hormo-
[3]. The lifetime risk of developing breast cancer in an nal therapy, radiation therapy, surgery and chemotherapy.
In individuals with distant metastasis, managements are
typically aimed at enhancing life quality and survival rate
*Correspondence: upr2014@yahoo.com
1
Department of Eastern Medicine and Surgery, Directorate of Medical [6]. The unpleasant side effects of breast cancer treatment
Sciences, GC University Faisalabad, Old Campus, Allam Iqbal Road, are one of the most motivating factors to find some alter-
Faisalabad 38000, Pakistan native methods. The use of herbs for treating the patients
Full list of author information is available at the end of the article
© The Author(s) 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License
(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium,
provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/
publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Akram et al. Biol Res (2017) 50:33 Page 2 of 23
having breast cancer is considered a natural alternative, possess one breast that slightly smaller than the other
because some plants may contain properties that natu- [29]. The epidermis of the areola and nipple is very much
rally have the ability to treat breast cancer [7–11]. pigmented and to some extent wrinkled, and the nip-
ple skin contains several apocrine and sebaceous sweat
Epidemiology glands and somewhat small hair. The 15–25 milk ducts
Currently, one in twelve females in Britain between go into the base of the nipple, wherever they expand to
age of 1 and 85 years gets breast cancer. With one mil- synthesize the milk sinuses. These milk ducts functions
lion new cases of cancers reported in the World, breast as the carriers of milk towards the nipples [30]. Slightly
cancer is common in females and comprises 18% of all under the surface of nipple, these sinuses end in cone-
women cancer. Incidence of breast cancer is predicted to shaped ampullae. The spherical areola is present around
increase to 85 per 100,000 women by 2021 [12]. In 2012, the nipple and is between 15 and 60 mm in diameter.
1.67 million new cases of breast cancer were diagnosed Sebaceous glands, sweat glands and lanugo hairs are pre-
that is 25% of all cancers among women. Ferlay et al. [13] sent on its skin, Montgomery’s glands, are big, modified
stated that 883,000 cases are in less developed countries sebaceous glands with tiny milk ducts that open into
and 794,000 in most developed countries. According to Morgagni’s tubercles in the areola epidermis. Deep in
the data, 145.2 women in Belgium and 66.3 in Poland the nipple and areola, several smooth muscle fibers are
between 100,000 suffer from breast cancer [14]. Inci- set circularly and radially in the dense connective tissue
dence of breast cancer in the United States is one out of and longitudinally alongside the lactiferous ducts that
eight women and In Asia one woman suffers from breast lengthen up into the nipple. These muscle fibers are cause
cancer out of 35. In Iran, there are 10 cases in 100,000 emptying of milk sinuses, nipple erection and contrac-
populations and 7000 new cases have been reported tion of areola. The greater part of the breast parenchyma
annually [15]. Prevalence of breast cancer is increasing in expand inferiorly from the point of the 2nd or 3rd rib to
Pakistan [16–18]. Breast cancer is found mostly in highly the inframammary fold, which is at about the point of
populated areas of South Asian developing counties [19, the 6th or 7th rib, and crossways from the border of the
20]. Breast cancers in males have been detected in North- sternum to the anterior axillary line. The mammary tis-
ern areas of Pakistan [21]. Yang et al. [22] stated that new sue also expands erratically into the axilla as the glandu-
cases of breast cancer in China were 168,013 in 2005 and lar tail of spence. The posterior surface of the breast rests
121,269 in 2000. on segment of the fasciae of the pectoralis major, rectus
abdominis muscles, external abdominal oblique and ser-
Anatomy of breast ratus anterior.
Both males and females have breasts [23]. The breast is
made up of fatty tissue called adipose tissue [24]. The A global prospective
female’s breasts usually contain more glandular tissue Globalization, which thus greatly characterizes our
than that of the males [25]. Female breasts contain 12–20 period, was primarily linked with commercial-related
lobes which are further divided into smaller lobules [26]. actions, consequently with ecological concerns, and espe-
These lobes and lobules are connected via milk ducts. The cially in recent times with the dark truth of terrorism. Up
adipose tissue of the breast is supplied by a network of till now the “globalization” of numerous human being
nerves, blood vessels, lymph vessels, lymph nodes, and is actions, together with health care, has been departing on
also composed of fibrous connective tissue and ligaments for several decades, enhancing in step with improvement
[27]. The female breast is designed to provide optimal in information machinery. Correctly or incorrectly, and
nourishment for babies and to provide sexual pleasure for whether planned or not, numerous clinicians in develop-
the female herself. The breasts are glandular organs that ing countries keep an eye on what Americans are achiev-
are very sensitive to hormonal changes in the body [28]. ing, or are alleged to be achieving, as “state of the art” and
They adopt cyclic changes in synchrony with the men- recent most excellent performance that ought to be cop-
strual cycle. They are closely associated with the genital ied. The actions reviewed and our current narration with
system of females. Nipple stimulation enhances secre- transplantation of bone marrow recommends that pre-
tion of prolactin from the pituitary gland. This hormone sent “standard of care” United States described interven-
also affects the uterus and can cause contractions. Lymph tions are inappropriate to global utilization. Unluckily,
node draining the breast tissues is also found in the arm- extensive deficiency of community wellbeing strategies
pits. After a female has had a baby and her milk comes in, to breast cancer has made understanding of such rights
mother may develop striking swelling under arms from for females not viable. Impractical, deadly, and extremely
engorgement of the breast tissue in that region. Breasts expensive treatments for breast cancer cannot assist the
come in all sizes and shapes, as do nipples. Most female
huge number of females in the earth at danger for or who is huge Invasive breast cancer is most occurring general
develop breast cancer [31]. carcinoma in females. The regions of elevated threat
are the prosperous populations of Australia and Europe
Types of breast cancer wherever 6% of females suffer from invasive breast cancer
According to site, it is divided into invasive and non- prior to 75 years of age. The prevalence of breast cancer
invasive breast cancers enhances quickly with increasing age [41]. Invasive breast
cancer that extends to different organs of the body is also
Non‑invasive breast cancer recognized as metastatic breast cancer [42]. Most com-
It is a cancer that has not extended away from the lob- mon organ to which these cells spread are brain, bones,
ule or ducts where it situated [32]. An example of a lungs and liver. These cells once more segregate and
kind of non-invasive breast cancer is ductal carcinoma expand irregularly and produce new cancers. The new
in situ. Ductal carcinoma in situ appears when atypi- forming cells are developing in different part of the body,
cal cells develop within the milk ducts, however have it is still breast cancer [43].
not extended to close proximity of tissue or outside. The
word “in situ” describes “in place.” Even though the atypi- Infiltrating lobular carcinoma (ILC)
cal cells have not extended to tissues outer the lobules or Infiltrating lobular carcinoma is also recognized as inva-
ducts, they can progress and grow into invasive breast sive lobular carcinoma. ILC originates in the milk glands
cancer. The normal background of every scientific unit (lobules) of the breast, but frequently extends to other
is demonstrated and a biological understanding of the areas of the body [44].
accessible information is presented. Lobular carcinoma
in-situ is understood merely a risky sign moderately Infiltrating ductal carcinoma
than a predecessor for the successive growth of invasive Infiltrating ductal carcinoma is also recognized as inva-
cancer, so that one time the judgment is made, addi- sive ductal carcinoma. IDC originates in the milk ducts
tional operative involvement is avoidable and sequential of the breast and extends to the duct wall, invading the
follow-up only is suggested. The management of ductal breast fatty tissues and probably other parts of the body
carcinoma in-situ should be kept in mind that breast- [45].
preserving treatment is at the present considered best
therapy of breast cancer, the illness we are attempting to Medullary carcinoma
stop [33]. The pitfalls of suggested management based on Medullary carcinoma is an invasive breast cancer that
retrospective statistics are have been taken into account designs a discrete margin normal tissue and medullary
and the requirement to conduct clinical studies intended tissue [46].
to establish the best possible beneficial treatment of non-
invasive breast cancer is affirmed [34]. Mucinous carcinoma
It is recognized as colloid carcinoma, mutinous car-
Lobular carcinoma in situ (LCIS) cinoma is a uncommon breast cancer created by the
This type of breast cancer develops into breast lobules mucus-forming cancer cells. Females with mutinous car-
[35]. The breast cancer has not extended exterior to the cinoma usually have an improved prediction than females
lobules into the breast tissue [36]. Lobular carcinoma with additional general kinds of invasive carcinoma [47].
in situ is usually identified as non-invasive breast cancer
[37]. Tubular carcinoma
Tubular carcinomas are a particular kind of invasive
Ductal carcinoma in situ breast carcinoma. Females with tubular carcinoma usu-
It is the most general kind of non-invasive breast cancer, ally have an improved prospects than women with addi-
is limited to the breast duct. Example of ductal carci- tional general kinds of invasive carcinoma [48].
noma in situ is ductal comedocarcinoma [38].
Inflammatory breast cancer
Invasive breast cancer Inflammatory breast cancer is the form of swollen breasts
It exists when abnormal cells from within the lobules or (red and warm) with dimples and/or broad ridges due to
milk ducts split out into close proximity of breast tissue cancer cells blocking lymph vessels or channels in the skin
[39]. Cancer cells can pass through the breast to different over the breast. Though inflammatory breast cancer is
parts of the body through immune system or the systemic uncommon and is tremendously fast-growing [49]. Treat-
circulation [40]. They may move early in the development ment involves vigilant synchronization of all multidisci-
when the tumor is a minute or afterward when the tumor plinary strategies, including radiation therapy, surgery,
chemotherapy and imaging. The administration of neoadju- through a chain of alteration from child bearing age to
vant chemotherapy has accorded considerably to enhance- senility. The changes seen with every menstrual cycle
ment in general survival from the time when the earliest and pregnancy guided us to assume the occurrence of
report of this matter and has performed the function of precursor cells in the mature tissue that is able of syn-
locoregional treatment such as radiation and surgery signifi- thesizing novel duct-lobular units [59]. The typical breast
cant to sustained improvements in this ailment [50]. architecture contains a stratified epithelium bordered by
a basement membrane and fixed in a template of blood
Paget’s disease of the breast vessels, lymphatic and stromal cells [60]. In the usual
It is the uncommon type of breast cancer that usually shows breast, the stratified epithelium comprised of two dissim-
visible changes to the nipple of the breast [51]. Its symp- ilar cell populations, myoepithelial and epithelial, which
toms include red itchy rashes involving the nipple and then can be distinguished by way of immunohistochemical
it can sometime spread to the normal skin as well. However staining with antibodies against myosin and CK, cor-
it resembles with the other skin conditions such as eczema respondingly. It has been postulated that the creation
and psoriasis but it can be differentiated as the other skin of cellular heterogeneity in breast disorders depends on
conditions usually affects both the breasts and can start the primary developmental series of the usual breast.
from the areola rather than the nipple of the breast how- This heterogenicity of the breast carcinoma might hap-
ever Paget’s disease of the breast most often affects only pen from the neoplastic change of either myoepithelial or
one breast and starts with the nipple of the breast instead epithelial cell, or yet from a stem cell that has the abil-
of areola (breastcancercare.org.uk) Nearly 1–3% of all the ity to develop into myoepithelial or epithelial cells [61].
breast cancers are Paget’s disease and can affect both men According to the oncology of breast cancer, neoplastic
as well as women. The actual theory behind the pathogene- cells differ from the normal body cells. Normal tissues
sis or development of Paget’s disease of the breast isn’t clear of the body have limited growth promotion and regula-
yet however there are few theories supporting it’s patho- tion which helps to keep the structure and functions of
genesis. Their warning signs include bleeding and oozing of tissues usual. However, cancerous cells have prolonged
discharge from the nipple, flattening or inversion of nipple, and chronic proliferation without any external stimuli
lump found in the breast etc. It can be diagnosed by using [62]. Cancer cells overcome the growth suppressor genes
punch biopsy. It’s prognosis is good if it remains within the [63]. Breast cancer is a malignant disease that initiates
nipple or in ducts of the breast [52]. in the breast cells. Like other malignant tumors, there
are numerous causes that can increase the possibility
Phyllodes tumor of developing breast cancer. Injure to the deoxyribonu-
Phyllodes tumors are can be either benign or malignant cleic acid (DNA) and hereditary alteration can guide to
[53]. Phyllodes tumors develop in the connective tissues breast cancer have been associated with the exposure of
of the breast and may be treated by surgical removal [54]. estrogen. Some patients inherit fault in the deoxyribo-
Phylloides tumors are extremely uncommon; fewer than nucleic acid (DNA) and genes like the P53, BRCA1 and
10 females die of this kind of breast cancer every year in BRCA2 among others. The patients with a family history
the United States [55]. of breast or ovarian cancer have possibility of develop-
ing breast cancer [64]. Neoplastic cells require consid-
Triple‑negative breast cancer erable potential to multiply and convert into a massive
Breast cancer is at the present extensively documented tumor [65]. The immune system usually tries to find out
that is a heterogeneous disorder with special sub-forms, cancer cells and cells with injured deoxyribonucleic acid
distinguished by means of their dissimilar clinico-patho- (DNA) and demolish them. Breast cancer might be out-
logical characteristics, prevision and responses to man- come of malfunction of such an useful immune defence
agement. Triple-negative breast cancer is described by and surveillance. Breast cancer commonly occurs due to
the deficiency of progesterone receptor, human epi- an association between genetic and environmental fac-
dermal growth factor receptor 2 and estrogen receptors. RAS/MEK/ERK pathway and PI3K/AKT pathway
tor expression [56]. This type is mainly destructive, defend normal cells from cell suicide. When mutation
commonly observed in premenopausal females, and is occurs in genes that are involved in encoding of these
responsible for 10–15% of cases in white females, with a protective pathways, the cells become unable of commit-
elevated occurrence [57]. ting suicide when they are no longer required which then
leads to development of cancer. These mutations were
Pathogenesis of breast cancer confirmed to be experimentally associated with estrogen
The breast is a complex tubulo-alveolar organ fixed exposure [66]. It was recommended that deformity in the
within an asymmetrical connective tissue [58], that go growth factors signaling can assist growth of malignant
cells. Over expression of leptinin breast adipose tis- obese women the fatty tissue can provide the estrogen
sue enhances proliferation of cell and cancer [67]. These as it is capable of producing it. This increase in hormone
are numerous growth factors signaling and other fac- production seems to increase the risk of breast cancer
tors that interrelate between epithelial cells and stromal in obese post menopausal women. Deficiency of vita-
cells. Interruption in these might result in development min D and lack of sun exposure is considered to be the
of breast cancer. In cancer cells, enzyme telomerase turns important cause of breast cancer [81]. It is found to be
away the chromosomal shortening and allows the exten- more in women than men [82]. The risk of breast cancer
sive replication of cells [68]. Tumor cells get their nutri- increases with age however rarely found before the age of
ents and oxygen supply by angiogenesis [69]. Cancer cells 20 years [83]. Carcinoma in one breast can increase the
break their boundaries and can enter into the blood, lym- risk by four times in another breast. While the patients
phatic tissues and other tissues of the body to produce a that have the history of ovarian, endometrial or colon
secondary tumor [70]. cancer have 1–2 times increased risk to develop breast
carcinoma [84]. A female who has had breast cancer has
Causative factors and associated risks of breast carcinoma an enhanced danger of occurring breast cancer in the
Breast cancer is the leading cause of death among Brit- other breast [85]. The minimal role of the gene has been
ish females who are 40–55 years of age. Breast cancer is established in the development of breast cancer. BRCA-1
more common in single women than in married women (breast cancer susceptibility gene) is considered to be
[71, 72]. The breast is an estrogen sensitive organ. Many the cause of 5–10% of breast cancer that is transferred
females who have been on birth control pills or estro- from either father or mother to the next generation.
gen replacement have found that the medications result The study indicates that right environmental conditions
in enlarged and often tender breasts. The activity of this are required for cancer promoting gene for expression.
medication, combined with the standard western high Certain families have been recognized with a genetically
fat, low fiber diet, which over-stimulates breast tissue, higher incidence of early onset breast cancer. If some
could be a trigger for breast cancer. Incidence of breast individuals of the female’s family have had a specific kind
cancer is higher in women above 50 years of age and 2 of cancer, female may have an enhanced danger risk of
cases per 1000 are reported in this age group. Epide- breast cancer [86]. The danger is maximum if the affected
miological investigations have also suggested that those family member had breast cancer at a juvenile period,
women who have many children possess lower risk of had cancer in both breasts, or if female is a close family
breast cancer than those women who have fewer chil- member. First-degree family members such as daughter,
dren. Incidence of breast cancer is 10.04% among all can- sister and mother are mainly significant in estimating
cers and, most commonly occurs in 40–50 aged women. threat. Numerous second-degree relatives such as an aunt
Mean age of breast cancer in Iranian women is 48 years and grandmother with breast cancer might also enhance
[73]. An association of clinic pathological characteristic threat. Breast cancer in a male enhances the danger for
and breast cancer subtypes has been determined in Ira- the entire close female relatives. Women who have a
nian women [74]. Breast cancer mostly occurs in obese positive family history of breast carcinoma are 2–4 times
women [75]. Depression is most commonly found in more likely to develop the cancer, especially the females
women with breast cancer [76]. Andsoy et al. [77] con- who are the carriers of BRCA1 or BRCA2 genes have the
ducted a study to investigate knowledge of colorectal, significant chance to develop carcinoma of breast [87].
cervical and breast cancer. For this study 226 working Breast cancer affects both male and females; though, the
nurses were screened. It is very interesting that certain prevalence is more in female as compared to male. Gen-
epidemiological studies have claimed that women who erally, females are at 100-fold increased danger of breast
give birth to their child before they attain the age of cancer than male [88]. Early menarche, nulli parity, preg-
20 years are known to have decreased risk of breast can- nancy after the age of 30, oral contraceptives or hor-
cer than those women who have not given birth to any mone replacement therapy all these factors can increase
child or who have given birth to their first child after the the risk of breast cancer [83]. Steroid hormones include
age of 30 years. The risk increases with age rapidly dur- androgens, progesterone and estrogen, which belong to a
ing premenopausal and slowly during post-menopausal cluster of structurally connected hormones known as sex
life. Breast feeding decreases the risk of breast cancer hormones that are released into the blood by the gonads
[78]. Menopause resulting from surgical removal of ova- and adrenal glands. They are synthesized from single
ries (oophorectomy) decreases the risk [79]. Presence of general precursor, cholesterol through a reaction cata-
certain kinds of benign tumours in breast increases the lyzed by numerous enzymes to make a large diversity of
risk of malignancy [80]. The ovaries stop producing the hormones for diverse target organs and tissues [89]. This
female hormones once the menopause sets in, but in procedure is well regulated and the discharge of these
hormones into the systemic circulation. These hormones carrier of these genes is 10–30 times more than those
cross the plasma membrane to reach the target cells and females that have no inherited gene variants. In spite of
bind to specific receptors called steroid hormone recep- the big boost in breast cancer danger linked with BRCA1
tors to exert their activity [90]. Oestrogens have impor- and BRCA2 genes, they are responsible approximately
tant activities on differentiation, growth and performance 5% of all breast cancers, as merely 1 in 1000 females have
of several tissues, including urogenital system of man and acquired one of them. There are several tribal Subgroups
women, cardiovascular system, brain, uterus and breast in which BRCA1 and BRCA2 genes are more possible to
[89]. In accordance with this, Kato et al. [91], reported be innate (e.g. approximately 1% of females of Ashkenazi
that the progression of reproductive organ cancer like Jewish descent have acquired increased risk BRCA1 or
prostate and breast cancer frequently occurs because of BRCA2 genes; analogous variants are moreover famil-
the androgens, progesterone and estrogen, which exert iar in women belong to Iceland and different Scandina-
numerous biological activities in normal as well as abnor- vian countries). Individual risk indicator as an outcome
mal cells. The study indicates that the development of of hereditary testing for BRCA1 and BRCA2 remains a
normal and abnormal epithelial cells of the breast can be demanding experience. Almost 2000 variants have been
modulated by stromal cells of the breast and can release found in the two genes (BRCA1 and BRCA2) and, for
growth factors after stimulation by the endogenous hor- numerous; it is yet not recognized whether or not they
mones. An aromatase enzyme is found in adipose tissues, enhance prevalence of breast cancer. One possible sign is
which makes estradiol from the precursor molecule, cho- the site of the variant in the gene; it indicates that vari-
lesterol. Fat cells are found in excess amount in breast of ants in few parts of the genes might cause bigger threat
aged females; therefore, the quantity of estradiol is higher of breast cancer than others [96, 97]. Even though all
in breast tissues of post menopausal female than their females who acquire a BRCA1 or BRCA2 variant do not
plasma level [92]. This most likely is responsible for the essentially cause breast cancer, it is uncertain what other
increasing occurrence of breast cancer in aged female determinants such as genetic or environmental persuade
and assists the action of steroid hormones in breast can- the risk of breast. There is also promising data that deter-
cer pathogenesis. Benign tumors and proliferative lesions minants for breast cancer might perform in a differ-
without or with atypia can increase the risk of breast can- ent way for carriers of BRCA1 or BRCA2 variants than
cer [85]. Breast cancer has been linked with high level for females lacking hereditary vulnerability because of
of dietary fats and low level of certain nutrients for vari- these genes [98]. Literature review also recommends that
ous years [93]. Animal fat stimulates colonal bacterial to high-risk genes other than BRCA1 and BRCA2 possibly
form estrogen from cholesterol found in the diet, thus enhance the risk of developing breast cancer, mainly for
increasing level of estrogen in the body. The body fat is younger females.
also involved in synthesis of oestrone, a type of estrogen.
Obesity, increased fat consumption, radiation therapy Mortality
[94]. Evidence is accumulating that certain environmen- Fifth most common cause of cancer death is breast can-
tal pollutants contribute to estrogenic activity and may cer. The mortality and age standardized prevalence of
contribute to the prevalence of breast problems in the breast cancer is higher in the United States compared
industrialized world. Alcohol consumption is linked with to world. In Poland, seventeen percent of disease cases
breast cancer risk. This association was felt to be second- occur due to cancer and 14% deaths occur due to can-
ary to the fact that consumption of alcohol enhances level cerous changes. Worldwide death due to breast cancer
of hormones in the blood [95]. calculated in 2004 was 519,000 [99]. In the United States
alone, approximately 1,208,000 cancer cases are reported
BRCA1 and BRCA2 per year and that some 538,000 people die from the pre-
These are two genes that have been recognized as pos- vious manifestation of this disease condition, represent-
sessing the firm relationship with breast cancer. Both ing about one fifth of the total annual deaths from all
emerge to contain comparable biological activities such causes [74].
as DNA damage repair and, in their variant kind, they
enhance the danger of breast cancer and other ovar- Stages of breast cancer
ian cancers. The preeminent knowledge accessible to According to the report of breast cancer.org Stages of the
date is based on a joint investigation of 22 researches, breast cancer depends upon the size and type of tumor
11 which established that the prevalence of breast can- and how much the tumor cells have been penetrated in
cer is 65% at 70 years of age in women who acquired a the breast tissues [100]. Whereas stage 0 describes the
BRCA1 gene and 45% in those women who are carri- non invasive and stage 4 describes the invasive kind of
ers of BRCA2 genes. The prevalence of breast cancer in tumor. Descriptions of those tumor stages are:
Stage 0 menopausal condition, earlier pregnancies and utiliza-

This is the non invasive stage of tumour which indicates tion of hormone replacement therapy after menopause
that both cancerous and non cancerous cells are within or utilization of oral contraceptives. Personal history as
the boundaries of that part of the breast in which the well as family history should be carried out in detail. Per-
tumor begins to grow and no evidence found of their sonal history includes age at diagnosis of breast cancer,
invasion in the surrounding tissues of that part, the previous breast biopsies and treatment of other cancer
example of this tumour stage is ductal cell carcinoma with use of radiations. Family history includes history
in situ (DCIS) [101]. of ovarian cancers and breast cancer in first degree rela-
tives. Patents should be examined for particular mani-
Stage 1 festations such as breast pain, weight loss, pain in bone,
This stage describes as the invasive breast carcinoma tiredness and nipple discharge [107]. Physical examina-
and microscopic invasion is possible in this stage. It has tion includes inspection of breasts, area around neck and
two categories that are 1A and 1B stage. The category collarbone, and armpits (axillae) carried out by clinicians
1A describes the tumor which measures up to 2 cm and [108]. Breasts are observed for any deformities such as
none of the lymph nodes are involved in it while stage lumps or other manifestations of breast cancer. Lymph
1B describes that small group of cancer cells larger than nodes are also examined that are usually enlarged in
0.2 mm founds in lymph node [102]. patients with breast cancer.
Stage 2 Self examination

Stage 2 also has two categories 2A and 2B. Stage 2A Usefulness of the breast self-examination is contentious
describes that the tumour is found in axillary lymph because the advantage in conditions of reduced deaths
nodes or in sentinel lymph nodes but no tumor found in has not been established [109]. Most physicians educate
breast. The tumor can be smaller or larger than 2 cm but females to carry out monthly BSE to become recogniz-
not more than 5 cm. However stage 2B describes that the able with their usual structure and authorize them with
tumor could be larger than 5 cm but can’t reach to the reference to their own healthcare [110]. Women are
axillary lymph nodes [103]. guided for self examination of the breast cancer. Women
can find abnormalities in size and shape of breast on self
Stage 3 examination [111–113]. Alipour et al. [114] conducted a
It has been divided into three sub categories that are 3A, study to investigate the the SMS based and paper based
3B and 3C. Amongst which stage 3A describes that no paper learner’s satisfaction and learning effect. Gynecolo-
tumor is found in breast but it can be found in 4–9 axil- gists gave printed materials and text messages regarding
lary lymph nodes or in sentinel lymph nodes while stage facts of breast cancer and breast cancer tests. Doctors
3B describes that the tumour can be of any size but have found higher motivation and better effects in the SMS
caused swelling or ulcer on the skin of the breast and can group than the printed material group. Sreedharan et al.
have spread up to 9 axillary lymph nodes or to sentinel conducted a study in United Arab States hospitals. Self
lymph nodes stage 3B can be considered as inflammatory administered structured questionnaire was used to inves-
breast cancer which includes red, warm and swollen skin tigate practices of self examination and knowledge. Satis-
of the breast. However stage 3C describes the spread of factory results were found from this study [115]. Ozkan
tumor up to 10 or more than 10 axillary lymph nodes and et al. [116] investigated the level of knowledge regard-
it also have involved the lymph nodes above and below ing self examination of the breast cancer among 113
the clavicle [104]. midwifery and nursing students. These researches have
shown that continuous education program about breast
Stage 4 cancer can raise the awareness among the population.
This is the advanced and metastatic stage of cancer and Ceber et al. [117] conducted studies on breast self exami-
this stage describes the spread to other organs of the nation and health beliefs of Turkish women and stated
body that is lungs, bones, liver brain etc [105]. that physical illnesses and early death can be prevented
by early diagnosis of breast cancer. He further stated
Diagnosis that one out of seven patients with breast cancer is diag-
History and physical examination nosed in time. Beydag and Karaoglan [118] investigated
The clinical history of patients with breast cancer is the awareness about breast self examination in 1st and
aimed at investigating cancer threat and demonstrating 4th years students and concluded that 4th years students
the occurrence or lack of manifestations indicative of have more knowledge about breast examination than the
breast illness [106]. It must comprise age at menarche, 1st years students.
Ultrasound breast imaging of loco-regional lymph nodal extent and/or far-away

There are numerous researches behind the application metastases not obvious by regular imaging, therefore
of adjunctive screening ultrasound in elevated hazard altering staging in up to 25% of the patients. This pro-
women with thick breast tissue, which reveals a signifi- cedure is employed for the management planning by
cant but established figure of false positives [119, 120]. describing spread of primary illness. It is also employed
There is no randomized clinical study conducted for in re-staging after management ailment relapse and
investigation of impact of screening ultrasonography on treatment follow up [125].
mortality rates of breast cancer. Entire breast ultrasound
might permit the Physicians to display for breast tumors Tumor markers
not measured by long-established mammography, par- Porika et al. [126] stated that tumour markers should
ticularly in thick breasts wherever mammography sen- be measured in all stages of the breast cancer including
sitivity is lesser [121]. Ultrasound breast imaging shows metastasis prediction, treatment, diagnosis and screen-
the size and position of tumour whether it is filled with ing. Thirteen verities of tumor markers of breast cancer
fluid or is solid and needs to be biopsied to rule out can- are measured, six out of 13 are novel for the guideline.
cer. This examination is quickly becoming a routine pro- The different varieties displayed proof of clinical use
cedure for diagnosing lumps in young women [122, 123]. and are suggested for utilization in practice [127]. It is
particularly significant that the comparative autonomy
Nuclear medicine of the markers in reference to other accessible markers
It is a type of molecular imaging wherever a radioactive to demonstrated so as to evade the gratuitous price and
substance (radiopharmaceutical) is introduced to an indi- expenditure of redundancy [128]. Furthermore, it is sig-
vidual and the radiation from the radiopharmaceutical nificant that the physician be attentive of the restrictions
is displayed by perceptive emission detectors including in together specificity and sensitivity of every marker so
gamma cameras and PET detectors and gamma Cameras because not to specificity and sensitivity of every marker
located exterior to the body of patient. Combination of so since not to over- or under-interpret the prognostic
CT and gamma camera and the combination of CT and worth of a few investigation. With these caveats in intel-
PET is a main progress in enhancing recognition and ligence, trial submission of tissue, germ-line and soluble
vicinity of disease. tumor markers can recover medical care of individuals at
threat for and with breast cancer.
Single photon emission computerised tomography
(SPECT) Ca 15‑3
This procedure utilizes solitary photon radionuclides It can be employed for monitoring of patients with breast
including gallium-67, iodine-131 and technicium-99 m cancer. High blood levels are seen in <10% of patients in
that discharge gamma rays. It is a efficient scan and is the beginning of breast cancer and in approximately 70%
precise for organ of curiosity. It can also be employed to of patients with advanced stage of breast cancer. The lev-
the entire body, is comparatively secure in expressions of els of CA 15-3 typically fall after successful management.
radiation quantity and is fine in recognition of primary However CA 15-3 can also be high in other types of can-
and metastatic cancers. Iodine-131 is together indicative cers and in few non-cancerous conditions including hep-
and remedial for cancer of thyroid [124]. atitis and benign breast conditions.
Positron emission tomography (PET/CT) Ca 27.29

In expressions of radiation quantity, PET/CT is also It is another marker for monitoring of patients with
comparatively secure and utilizes positron emitting breast cancer. This test does not seem to be any better
radionuclides including oxygen-15, flouoride-18 and to identify early or advanced stage of breast cancer. This
carbon-11. The frequently utilized tracer in positron tumor marker is seen in other types of cancers and in few
emission tomography is a radioactive type of glucose non-cancerous disorders.
such as [18F]fluoro-2-deoxy-d-glucose. Tissues with
enhanced metabolic requirements including develop- Estrogen and progesterone receptors
ing cancer cells, demonstrate increased uptake of the For the identification of breast cancer, breast cancer
tracer and displays on the scan. With combination of tissues are investigated for estrogen and progester-
CT and PET, significant information regarding numer- one receptors including HER2 antigen. These tests give
ous situations affecting the different organs of the body information regarding the aggressiveness of cancer and
is simply mapped. PET/CT is extremely perceptive response of certain drugs used for treatment of breast
and precise for predicating occult and different areas cancer.
Immunohistochemistry uneasiness at what time the anesthetic is given [136].

Immunohistochemistry (IHC) has grown to be an essen- MRI, ultrasound and mammogram can be used to guide
tial component of pathology. Although eosin and hema- the prickle for the duration of core biopsy [137].
toxylin stain is the primary foundation for diagnostic
pathology of the breast, Immunohistochemistry stains Vacuum‑assisted stereotactic core biopsy
give valuable and sometimes very important information. In this core biopsy, different tiny tissue samples are taken
Furthermore, taking into consideration the part of hor- via single tiny incision in the skin with a prickle and a
monal treatment in hormone receptor–positive breast suction-type device [138]. It is carried out using local
tumors, as well as the accessibility of targeted chemo- anaesthetic. MRI, ultrasound or a mammogram may be
therapeutic drugs for HER2-positive patients, Immu- employed to direct the prickle into position. The patient
nohistochemistry knowledge indicates a key element of may experience little uneasiness during the process [139].
workups. Careful use of Immunohistochemistry stains
in combination with E & H test assists determine mainly Surgical biopsy
diagnostic matters encountered by clinicians during their If the abnormal vicinity is too minute to be biopsied by
routine practice. Clinicians should be well-known to uti- another procedure or the biopsy outcome is not appar-
lize the each immunostain and its restrictions to evade ent, a surgical biopsy is carried out. Prior to the biopsy,
errors in interpretation. Immunohistochemistry stains a guide wire may be placed into the breast to assist the
assists in differential diagnosis of challenging epithelial medical doctor locate the abnormal tissue. Local anes-
disorders of the breast. They should be selectively and thetic can be used and the physician may use MRI, ultra-
sensibly utilized and their results must be understood sound and mammogram to direct the wire into position.
with the differential diagnoses in consideration and with The biopsy is after that carried out under a general anes-
an understanding of potential drawback [129]. thetic. Little area close to breast tissue and lump are
detached, alongside the wire [140, 141].
MRI and breast cancer
Mammography has been considered as an appropriate Digital mammography
screening method for breast cancer detection for many It helps to find lumps in dense tissue. The image can also
years [130] but it can’t distinguish between the solid and be easily stored and transmitted to another radiologist
cystic masses and can miss up to 10–15% of the cases for a second opinion [142–144]. Tarhan et al. [12] stated
however MRI provides more accurate results and clear mammography may give false negative and false positive
benefit to the women who are developing breast cancer results in patients with dense breast tissues. Kanaga et al.
due to the BRCA1 and BRAC2 genetic mutation and are [145] stated that the practice of mammography is 19% in
present with the axillary lymph adenopathy [131]. Malaysian women as compared to other study which was
10.5%. Lack of health insurance coverage, low income
Breast biopsy and embracement were the main barriers to mammog-
Breast biopsy is the simply best technique for diagnosing raphy as mentioned in earlier studies. Mammography is
breast cancer [132]. There are numerous different types considered as the gold standard test for early detection
of breast biopsies. To enhance diagnostic precision and of breast cancer [146] but in case of scarce resources in
get rid of as many false negative results as possible, breast some areas in breast health awareness program should
imaging, clinical breast examination and biopsy are per- be promoted for the early detection of breast cancers and
formed concurrently (triple test). the staff should also gets the training of clinical breast
examination so that the patient get diagnosed at earlier
Fine needle aspiration stage especially in those areas where mammography is
A thin prickle is employed to get cells from the abnormal unavailable [147].
area or a breast lump [133]. Ultrasound can be used to
assist direct the prickle. A restricted anesthetic might be PEM and MRI in breast cancer patients
used to anesthetize the region where the prickle will be Hence both the positron emission mammography and
inserted [134]. magnetic resonance imaging have proven breast can-
cer detection sensitivity, however hormone replace-
Core biopsy ment therapy, post menopausal status and breast tissue
A wider prickle is to get a portion of tissue (a core) density has no influence on the sensitivity of PEM and
from the abnormal area or breast lump [135]. It is typi- MRI. Positron emission mammography can be used as an
cally made under restricted anesthetic, thus breast is alternative of MRI in patients who don’t want to have an
insensitive, while patient may experience little hurt or MRI due to multiple reasons such as time issues, limited
budgets, lack of interest, claustrophobia (fear of being Psychological adjustment to breast cancer
kept in as small space) [148]. However, both have the Breast cancer is extremely common and very worrying
similar sensitivity to detect cancerous lesions compre- experience for numerous females every year in devel-
hending invasive and ductal carcinoma in SITU [149]. oping and developed countries [159]. Psychological
research has given an image of the emotional and com-
Treatment munity impact of breast cancer on females’ lives, and
In the management of breast cancer, aim is to preserve of factors linked with better versus worse amendment.
quality of life with prolonged life expectancy. The use Psychosocial mediations have been helpful in reducing
of bioflavonoids may inhibit estrogen formation [150]. patients’ grief and improving their life quality. Current
Effective communication between doctors and patients study also recommends that psychological aspects might
plays an important role to improve clinical outcome. be associated with potentially significant biological ail-
Oshima et al. [151] reported that effective communica- ment linked processes. Additionally, to giving an idea of
tion between doctors and patients is effective. A study the psychological aspects in breast cancer, investigation
conducted in Japan indicates that this communication in this vicinity has given a foundation for further studies
helps the patients to cope with adverse effects. Doc- on adjustment to health-related nervous tension in com-
tor patient communication enhances the quality of life mon [160].
of breast cancer patients [152]. Previous studies have
shown that less exposure from radiations, higher family Surgery
monthly income, long years after diagnosis, higher edu- This is the foremost management strategy for individuals
cation, initial stage cancer and younger age were consid- whose breast cancer has not extended to further areas of
erably related with better quality of life (QOL) in patients the body and is also a choice for further complex stages of
with breast cancer [153]. Breast cancer is less common the illness [161–163]. The kinds of breast cancer surgery
in breast feeding women, but the protective effect of this vary in the quantity of tissue that is excised with the can-
factor is not clearly investigated [154]. Cancer is a fatal cer; this depends on the cancer’s characteristics, whether
disease affecting humankind in every country. Vinblas- it has extended, and the patient’s special feelings. A few
tine and vincristine was introduced in 1961 as anti can- of the most familiar kinds of surgery include:
cer drugs. CIPLA has improved the process of isolating
vinblastine and vincristine in the World [155], and India Lumpectomy (breast conserving surgery)
is exporting these alkaloids to European countries and Some patients diagnosed with breast cancer undergo
the demand is steadily increasing. The main forms of some type of surgery [164]. According to American can-
treatment for cancer in humans are surgery, radiation cer society, lumpectomy or partial mastectomy is the
and chemotherapeutic agents. The drugs can often pro- procedure of removing the part of the breast that con-
vide temporary relief of symptoms, lengthening of life tains malignant tumor along with some healthy tissues
and occasionally cures the disease. Many hundreds of and surrounding lymph nodes leaving the major part of
chemical drugs of known classes of cancer chemothera- the breast intact as possible [165]. This practice gener-
peutic agents have been synthesized [156]. The activity of ally experienced in women that are in their initial phase
these compounds is based on their capacity for biologi- of cancer, however the patient also requires another type
cal alkylation. The effective dose of such alkylating agents of treatment such as radiation therapy, chemotherapy or
was almost the same as the toxic dose. Multi-targeted hormone replacement therapy along with this procedure.
therapy could be more effective, because the recurrence Most surgeons and patients prefer lumpectomy initially
rate of cancer is high and death occurs due to metastasis. rather than having the complete breast removal, espe-
Deng et al. [157] reported that Pemetrexed and Lobapl- cially if the patient is more concerned about losing her
atin is prescribed in metastatic breast cancer. Huang and breast [166]. However, adverse effects of lumpectomy
Cao [158] reported that cantharidin sodium injection is are tenderness, temporary inflammation, sclerosis and
effective in the management of breast cancer. Cantharidi- changed appearance of breast, etc [167].
nate sodium injection is herbal origin and is prepared in
China for treatment of breast cancer. Breast cancer man- Mastectomy
agement strategies differ depending on the step of the Mastectomy is done to decrease the risk of development
cancer—its mass, place, whether it has extended to other of breast cancer [168]. Bilateral prophylactic mastectomy
organs of the body and the physical condition of the indi- decreases the chances of development of breast cancer
vidual. Present management for breast cancer includes but does not eliminate the risk of developing cancer com-
targeted therapies, hormonal treatment, radiation ther- pletely [169]. Aromatase and tamoxifen decreases the
apy and surgery. risk of contra-lateral breast cancer and it is considered
more effective than contra lateral prophylactic mastec- randomized clinical studies demonstrates a momentous
tomy [170]. Mastectomy is considered the most effective enhancement in overall survival and disease-free survival
method of dealing with an already diffused case of breast for females whose ovarian ablation were performed as
cancer, for which a lumpectomy was not decisive enough. adjuvant treatment compared to those females who did
Nevertheless, the loss of breast leads to feeling of asexu- not. Literature review indicates that ovarian ablation
ality and loss of self-image and consequent depression in may be employed an alternative therapy for breast cancer
most women [171]. [176].
Reconstructive surgery Role of estrogen and progesterone receptors in the

Females who have a mastectomy might as well have management of breast cancer
breast renovation, either immediate reconstruction or The estrogen receptor assay has developed into a typical
delayed reconstruction. It is performed to get better the practice in the treatment of complex breast cancer [177].
look of the breast following tumor surgery. All females Tumors missing estrogen receptor react occasionally to
having a mastectomy must be presented the option to endocrine treatment, while improvement proportions of
converse reconstructive surgical treatment [172]. Mas- 50–60% are seen in estrogen receptor positive tumors.
tectomy is a comparatively simple surgical practice that Current researches demonstrate that the estrogen recep-
typically results in stay in hospital for 1–2 days. Defi- tor condition of the principal cancer is a superior inter-
ciency of the breast mass changes the patient’s special preter of the endocrine reliance of metastatic cancers at
look and can create wearing a few forms of clothing dif- the moment of clinical deterioration. Additionally, the
ficult. The utilization of an exterior prosthesis to tackle deficiency of estrogen receptor in the primary cancer is
these problems can be awkward and scratchy, particu- an significant self-regulating predictive display of higher
larly for females with huge breasts. Though, the most incidence of relapse and shorter survival. Quantitative
significant issue of mastectomy is the psychosocial effect investigation of estrogen receptor and an analysis for
of the physical and aesthetic distortion, which can com- progesterone receptor are two procedures for enhanc-
prise nervousness, sadness, and negative impacts on ing the precision of selecting or rejecting individuals for
body figure and on sexual activity [173]. Breast recon- hormonal treatment; cancers with a elevated quantitative
struction is commonly requested by females with breast estrogen receptor amount or those with a positive pro-
cancer who are unable for breast-conserving treatment gesterone receptor show the maximum response. Initial
and females with an increased hereditary danger for investigation demonstrates that the existence of proges-
breast cancer. Existing breast reconstruction procedures terone receptor might be a improved indicator of tumor
are miscellaneous and might engage the utilization of hormone dependence than quantitative estrogen recep-
prosthetic implant or an autologous tissue flap, or both. tor [178].
Despite of the method employed, cancer might relapse
in the reconstructed breast; additionally, in autologous Anti‑estrogen therapy
tissue flaps reconstructed breasts, little complexity such It can be used in such types of cancers that are affected
as fat necrosis may take place. Researches recommend by hormones and the tumor has hormone receptors such
that breast reconstruction restores body representation, as estrogen receptors. Clarke et al. [179] stated that the
proves vigor, femaleness, and sexuality; and optimistically most common category of drugs that are used in breast
influences the patient’s feelings of comfort and life quality cancer is anti estrogen, which includes the agents that are
[174]. (tamoxifen, raloxifene, toremifene etc). Tamoxifen inhib-
its the hormone oestrogen from entering into cells of the
Ovarian ablation as adjuvant therapy for breast cancer breast cancer. This mechanism inhibits the breast can-
Ovarian ablation has been employed as management cer cells from developing. Tamoxifen can be suggested
for breast cancer [175]. There are numerous techniques to treat female of any age group. However tamoxifen
of ovarian ablation such as radiation induced ablation, is considered as the drug of choice in women that have
surgical removal of ovaries and chronic utilization of positive estrogen receptor breast carcinoma. Tamox-
luteinizing hormone-releasing hormone (LHRH) ana- ifen is a selective estrogen receptor modulator (SERMS)
logs. Additionally, there are few proposals that cytotoxic and acts like estrogen on other parts of the body such
chemotherapy might perform by inducing ovarian abla- as uterus. However, it demonstrates anti estrogen prop-
tion in premenopausal females with breast cancer. Of erties of breast tissues and competes with estrogen for
the abundant case series and clinical studies of ovarian binding to the estrogen receptors in the breast [180]. If
ablation conducted in the earlier period, numerous have we have to discuss about the toxic effects of anti estro-
been laden with methodologic issues. Meta-analysis of gen therapy, comparatively there is very least toxicity
found in it as compared to other cytotoxic drugs [181]. risk decline of breast cancer prevalence in the raloxifen
While some patients withdraw the treatment before com- treated patients as compared to the placebo group [193].
pleting the course of drug due to the side effects such A randomized clinical study of Raloxifen and Tamox-
as hot flushes, gastro intestinal problems and vaginitis ifen was planned for comparing the efficacies of ralox-
etc. Though, the medical indications for discontinuing ifen and tamoxifen on postmenopausal females with an
antiestrogen therapy include adeno carcinoma, sarcoma enhanced 5-year threat of breast cancer as expected by
and thrombo embolic diseases etc. Any how the Ameri- the Gail model [194, 189]. The study demonstrated that
can society of clinical oncology recommends Tamoxifen raloxifen was comparable to the tamoxifen in decreasing
as standard adjuvant therapy for patients with Estrogen the threat of invasive breast cancer and was linked with
positive breast carcinoma [182]. On the other hand Ful- a minor danger of cataract and thromboembolism than
vestrant; Faslodex has entirely anti estrogenic action and tamoxifen. In 2007, approximately 10 years following the
is considered as estrogen antagonist it demonstrates anti endorsement of tamoxifen, the FDA permitted raloxifen
neo plastic activities in breast tissues without having a for the impediment of breast cancer for postmenopau-
positive effect on the uterus and bones, which may lead sal females with osteoporosis and for postmenopausal
to certain side effects if taken for a long period of time females at increased danger for breast cancer. In Aus-
such as osteoporosis [183]. Tamoxifen and raloxifene are tralia, tamoxifen is prescribed for the treatment of breast
selective estrogen receptor modulators (SERMs), a set of cancer and osteoporosis.
medicine that selectively prevents or motivates oestro-
gen-like activity in different tissues, affecting the estrogen Aromatase inhibitors
receptors [184]. Tamoxifen exhibits its oestrogen antago- These are compound designed for decreasing oestrogen
nist action in numerous tissues such as uterus, liver, bone formation by targeting aromatase, the enzyme complex
and breast [185]. It was used as adjuvant treatment in accountable for the last stair in the formation of estro-
estrogen receptor positive patients and tamoxifen was gen [195]. The third-generation aromatase inhibitors
accepted by the United States Food and Drug Adminis- including letrozole, exemastane and anastrozole are in
tration (FDA) in 1998 for the impediment of breast can- present utilization [196]. Randomized clinical trial con-
cer for females at elevated danger [186]. This verdict was ducted for investigation of these agents in the treatment
based on the outcome of a experiment carried out by the of breast cancer has indicated that these compounds con-
United States National Cancer Institute that was inter- tain an outstanding effectiveness in treating females with
rupted premature as an intervening study indicated that advanced disorder. Clinical study indicated that females
tamoxifen decreased breast cancer prevalence by approx- managed with aromatase inhibitors had a superior contra
imately one half [187, 188]. Four big prospective studies lateral breast cancer threat decline than females managed
have investigated the efficacy of tamoxifen versus placebo with tamoxifen [131].
for breast cancer danger decline for females at elevated
danger of breast cancer [189]. A summary of these stud- Radiation therapy
ies demonstrated a 38% general decline in breast cancer It is useful for reducing the necessity of mastectomies. A
occurrence for females at increased danger of breast can- combination of a lumpectomy and radiation therapy is
cer who administered tamoxifen for the period of 5 years being increasingly used over a mastectomy in the early
and also indicated that tamoxifen inhibits only estrogen stages of breast cancer [197]. A study was conducted in
receptor positive breast cancers (RR ~ 50%) with no India. For this study 135 women were selected, most of
influence on estrogen receptor negative breast cancer them had undergone mastectomy. At the time of analysis,
[190]. A variety of adverse effects have been reported there was no local recurrence after hypo fractioned radi-
for females taking tamoxifen, such as venous thrombo- ation therapy and metastatic disease developed in only
sis, cataract, endometrial cancer, menstrual disorders four patients [198]. Zhou et al. [199] reported that radia-
and hot flushes. A study indicated that the risk decreas- tion therapy is effective in early breast cancer patients.
ing activity of tamoxifen expands beyond the vigorous This study was conducted on 143 women who underwent
management phase of 5 years, and remains for minimum either routine or intra operative radiation therapy after
10 years, whereas the majority of adverse reactions do breast conserving surgery. At 54 months of follow up,
not carry on behind the 5 year management duration there was a significant local control of the tumour. High-
[191]. Raloxifene, has also been revealed to decrease energy rays from radiation therapy kill cancer cells. This
danger of breast cancer, however seems to exert some therapy affects only the cells that are treated. Use of radi-
adverse reactions [192]. During the precedent periods, ation therapy may be done after breast cancer surgery to
clinical studies carried out to investigated the efficacy of destroy the remaining cells in the chest area.
raloxifen on fracture and osteoporosis, showed a 44–76%
Brachytherapy Thermochemotherapy
It is a kind of radiotherapy [200]. It might be recognized Medifocus heat management in combination with chem-
as accelerated partial breast irradiation. It directs radia- otherapy enhanced the shrinkage of median cancer in
tion merely to the area around the vicinity wherever the the thermochemotherapy arm to 88.4%, whereas for
cancer was. This might replace the requirement to pro- chemotherapy alone the shrinkage of median cancer was
vide radiation to the whole breast. It also decreases the 58.8%. For the thermo-chemotherapy management arm,
number of management sessions [201]. approximately 80% of breast cancers had a cancer size
decrease of 80% or more, compared to merely 20% for the
Chemotherapy chemotherapy alone [214].
The process of killing cancer cells by using certain
medicines is termed as chemotherapy [202, 203]. It can Complementary therapies
be given in both situations, before and after surgery, Women with breast cancer occasionally desire to use
depending upon the condition of the patient. According complementary therapies along with their medical ther-
to the American cancer society the medicines include apy [215]. These therapies are usually not investigated in
in chemotherapy are Docetaxel, Paclitaxel, Platinum randomized clinical trials [216]. Some female believe that
agents (cisplatin, carboplatin), Vinorelbine (Navelbine), they have benefited from a number of these treatments
Capecitabine (Xeloda), Liposomal doxorubicin (Doxil), [217]. Vitamins, nutritional supplements, yoga, medita-
Cyclophosphamide (Cytoxan), Carboplatin (Paraplatin) tion, visualization, traditional medicines and acupunc-
etc [204]. However it has various side effects [205]. Meta- ture are included in complementary therapies.
static or secondary breast can is difficult to treat but it
can be controlled and sometime for various years [206]. Medicinal plants
Chemotherapy can be prescribed to manage metastatic Medicinal plants
breast cancer to minimize or sluggish its development. Screening of plant extracts for anticancer activity started
It can also be administered to decrease some manifesta- in 1961 by National cancer institute in the USA, and
tions. Other treatment option can be initiated prior or up to 1981 (20 years) about 1,14,045 plants had been
alongside chemotherapy. screened of which only 3.4% (representing about 3400
different species) have been observed to be active in one
Taxol or more biological systems.
Taxol is used clinically in the treatment of ovarian can-
cers and is undergoing clinical trials against metastatic Ganoderma lucidum (Polyporaceae)
breast cancers [207]. It may also have potential value It contains ganoderic acid, ganoderic acid G, ergosta,
for lung, head and neck cancers. Taxotere is a side chain ergosterol peroxide ganoderic acid G, ergosta, ergosterol
analogue of taxol, which has also been produced by semi peroxide, methyl ganoderate A, B, ganoderic acid C2. It
synthesis from 10-deacetyl-baccatin III [208]. It has is an anticancer [218]. Jiang et al. [219] reported that the
improved water solubility, and is being clinically tested Ganoderma lucidum suppresses growth of breast cancer
against ovarian, and breast cancers. It can be used in cells through the inhibition of Akt/NF-kappa B signaling.
those where resistance to cisplatin has been observed It is used to treat cancer cells. It inhibits the transcription
[209]. factor NF-kappa B and inhibits the invasive behavior of
breast cancer cells. The exact mechanism for inhibition
Anthracyclines of cancer cells is not understood. The study showed that
Anthracycline are commonly prescribed in the treatment the proliferation of breast cancer MDA-MB-231 cells is
of breast cancer [210]. They impede with enzymes associ- inhibited and Akt/NF-kappa B signaling is suppressed.
ated the DNA copying, which is desired for cells to sepa- Phosphorylation of Akt at Ser473 is suppressed by this
rate to create new cells. Epirubicin and doxorubicin are plant and expression of Akt is suppressed, as a result NF-
the most commonly used medicines in breast cancers. kappa B activity in MDA-MB-231 cells is inhibited.
There is proof that anthracyclines functions better than
various other chemotherapy medicines [211]. However Momordica charantia (Cucurbitaceae)
these have adverse reactions such as damage to the heart The parts used are fruits, leaves and seeds. It contains
and loss of hair [212, 213]. Prior to start of medicines, glucoside, albuminoids, fatty acids, non polar lipid,
patient should converse with clinician any probable linolinic acid, palmitic acid, myrtenol, hexenol, benzyl
adverse reactions of drugs used and how these medicines alcohol, acylglycosylsterols and glycoproteins [220]. It
might influence life quality. 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 Indole‑3‑Carbinol (13C)
charantia extract inhibits breast cancer by modulating A compound known as indole-3-carbinol, which is a
cell cycle regulatory genes. This study was conducted plant chemical derived from cruciferous vegetables such
in vitro models. An extract of this plant was investigated as Brussels sprouts and cabbage, changes the way estro-
in human breast cancer cells, MCF-7 and MDA-MB-231, gen is metabolized. This compound predictably alters
and primary human mammary epithelial cells. This the endogenous estrogen metabolism towards increased
extract was able to decrease cell proliferation and apop- catechol estrogen production and may thereby provide a
totic cell death was induced. Survivin and claspin expres- novel dietary means for decreasing risk of breast cancer
sion was inhibited by this extract. [236].
Carthamus tinctorius (Asteraceae) Silibinin and Chrysin

The parts used are flowers and seeds. It contains pal- Previous research indicates that chrysin and silibinin
mitic acid, hexadecanolenin, coumaric acid, daucos- function synergistically and possess significant anti-
terol, apigenin, kaempferol, trans-3-tridecene-5, 7, 9, cancer activities against T47D breast cells [187, 188]. It
11-tetrayne-1, 2-diol, trans-trans-3, 11-tridecadiene -5, shows potential that the synergistic efficacy is based, at
7, 9-triyne -1, 2-diol [223]. It is used in colds, flu, fevers, least in part, by down-regulation of hTERT and cyclin
hysteria, anemia, and diabetes mellitus. It is an anti- D1. Their potential activities in the established synergism
oxidant [224] and alpha glucosidase inhibitor [225]. Loo among Chrysin and Silibinin should be verified by addi-
et al. [226] reported the efficacy of this plant in breast tional in vitro or in vivo researches. Study demonstrates
cancer. MDA-MB-231 breast cancer cell and normal that Chrysin and Silibinin combined might come out as
human mammary gland cell were treated with a com- an eye-catching approach based on herbal medicine for
pound that contains Carthamus tinctorius. This com- the management of breast cancer [237].
pound observed inhibition of cell proliferation. Inhibition
of cell proliferation was dose dependent. Its cytotoxic Lactobacillus acidophilus
activity was more than commonly used cytotoxic drugs. Breast cancer and hyperestrogenism may be decreased by
the inclusion of lactobacillus acidophilus in the diet. This
Viscum album (Viscaceae) useful bacterium helps to metabolize estrogen properly
Part used are leaves and stem. It contains sinapylfla- in the bowel. Clinicians can prescribe lactobacillus acido-
vanone, glucopyranoside, flavanone, hydroxy flavanone philus that is available in different forms, including cap-
and viscin [227]. It is antioxidant, cardiac tonic, and anti- sules in patients with breast cancer [238].
cancer [228]. It is used in palpitation, vascular spasms,
asthma, dizziness, vertigo and headaches. Gunver et al. Selenium
[229] reported the efficacy of this plant in breast cancer. Women with breast cancer have been shown to possess
selenium levels that are lower than those of women with-
Calendula officinalis (Asteraceae) out cancer. Selenium is a trace mineral that is often lack-
The parts used are leaves. It contains triterpene, calen- ing in refined food diets. A contrary association exists
dula glycoside, butyl ester, flavonol glycosides, and carot- among the prevalence of human breast cancer and con-
enoids [230]. It is anti-inflammatory and anti-cancer centration of dietary selenium. The adding of Selenium to
[231]. It is used in carcinoma of the vagina, and cervix. the food has been revealed to reduce the occurrence of
Pommier et al. [232] reported the efficacy of Calendula breast cancer [239].
officinalis for the prevention of acute dermatitis during
irradiation for breast cancer. Targeted therapies
These are drugs prescribed to manage some types of
Citrullus colocynthis (Cucurbitaceae) breast cancer. The mainly familiar targeted treatment
The parts used are seeds and fruit. It contains phytos- is the drug Herceptin [240]. It is prescribed to manage
terol, flavones C-glycosides, saponins, aspartic acid, HER2 positive breast cancer. It functions by preventing
arginine, colocynthin, colocynthitin and cucurbitacin the cancer cells from developing and progressing [241].
glycosides [233]. It is used in constipation and carci-
noma of the breast [234]. It is an emmenagogue, ecbolic, Gene therapy for carcinoma of the breast
cathartic, hydragogue and antioxidant [235]. This plant Gene therapy is a remedial strategy that is considered to
has growth inhibitory activity. Cucurbitacin glucosides correct particular molecular deformities associated with
have been isolated from this plant. These glycosides pre- the progression or development of breast cancer [242].
vent human breast cancer cells [234]. Mutated BRCA1 and p53 genes recognized as cancer
susceptibility gene are involved in progression of can- cells in normal and malignant tissue of the breast. The
cer [243]. Since mutational inactivation of gene activity investigations of these stem cells have assisted to clarify
is reserved to cancer cells in these contexts, cancer gene the source of the molecular complexity of breast cancer
modification techniques may give an opening for selec- in human. The cancer stem-cell theory has significant
tive targeting without major hazards of normal, non- role for timely recognition, prevention, and manage-
cancer cells [244, 245]. Both BRCA1 and p53 emerge to ment of human breast cancer. Dysregulation of stem
restrain tumor cells that lack mutations in these genes, cell renewal pathways are involved in the development
indicating that the so-called gene modification tech- of both sporadic and hereditary breast cancers. These
niques may contain broader efficacy than previously abnormal stem cells may give targets for the improve-
considered. Raising awareness of cancer genetics has rec- ment of cancer prevention options. In addition, since
ognized these and new genes as possible targets for gene breast cancer stem cells may be extremely challenging to
substitute treatment [246]. Early patient study of BRCA1 chemotherapy and radiation, the progress of additional
and p53 gene therapy have given a number of indications efficient treatments for breast cancer may need the effi-
of possible effectiveness, but have also recognized areas cient targeting of this cell population [252].
of clinical trials that are wanted prior to these therapeu-
tic strategies may be broadly employed in patients with Anti‑oestrogens and prevention of breast cancer
breast cancer [247]. With the accomplishment of anti-oestrogens in breast
tumor management, numerous studies evaluated their
Oncogenes inactivation use as an mediator to avert breast cancer in female
Numerous oncogenic proteins have been recognized at high risk [253, 254]. Tamoxifen is the antiestrogen
and linked with a variety of cancers [248]. The frequently medicine employed most commonly in the treatment of
practical strategy in clinical studies is the employment of breast cancer. Administration of tamoxifen as an adju-
antisense options. Oncogenes transcription also can be vant treatment following surgery, normally for 5 years,
prevented by means of adenoviral gene E1A, which hin- decreases the risk of hormone receptor breast cancer
der erbB-2 transcription, an option helpful in managing recurrence.
cancer that over express this oncogenic protein [249]. Metastatic breast cancer is also managed by tamox-
ifen. In numerous females, tamoxifen induce the mani-
Augmentation of cancer suppressor genes festations of menopause such as mood swings, vaginal
The mutations in tumor suppressor genes are linked with discharge and hot flushes. Toremifene is one more medi-
the development of numerous cancers. Some clinical cine strongly related to tamoxifen. It is used an alter-
studies are being conducted to deliver p53 via adenoviral nate drug in postmenopausal female for the treatment
vectors to different cancers. Likewise, viral vectors have of metastatic breast cancer. Fulvestrant is another drug
been used to administer a breast cancer gene BRCA1 and that decreases the estrogen receptor numbers. It is usu-
retinoblastoma gene into ovarian cancer and bladder, ally useful in postmenopausal female, even in tamoxifen
correspondingly. In various circumstances, this strategy resistant breast cancer. In previous studies, tamoxifen
will fall short, as the mutant gene indicates dominant was evaluated for its efficacy in 13, 388 females at higher
negative activity of the normal gene. To avoid this dif- risk of breast cancer for the period of 5 years. The study
ficulty for p53 gene therapy, a genetic repair approach indicated a 49% decrease in risk of increasing invasive
rather than a gene augmentation strategy might be more breast cancer and as well decreased risk of opposing side
successful [250]. breast cancer, reappearance and extended existence in
the female who had tamoxifen as accessory after opera-
Cancer stem‑cell therapy for breast cancer tion [187, 188]. Antioestrogens are currently suggested
Current investigation in biology of breast has provided as chemoprevention for female with atypical hyperplasia,
the foundation for the cancer stem-cell hypothesis [251]. genetic tendency to develop cancer and important family
Two significant aspects of this theory are that cancer history of breast tumor. They are also prescribed because
arises in progenitor cells or mammary stem cells as an component of practice post-operative concomitant man-
outcome of dysregulation of the normally strongly regu- agement of those with estrogen receptor positive cancers
lated method of self-renewal. As a consequence, cancers for duration of 5 years following surgery [255].
posses and are obtained by a cellular subcomponent that
keeps central stem-cell functions such as self-renewal, Human monoclonal antibody
which directs differentiation and tumorigenesis that is Monoclonal antibodies are prepared in the labora-
responsible for cellular heterogeneity. Development in tory [256]. These are used alone or in combination
the stem-cell field have guided to the recognition of stem with radiation therapy and chemotherapy to locate and
target cancer cells. Usually, the body’s immune system with impediment strategies long prior to cancer start
attack to foreign antigens such as infectious agents. It and develop [260]. Numerous prescription and non-pre-
will then create antibodies to assist fight it off. The scription medicines are now accessible for utilization in
body does not identify cancer cells as a kind of foreign angioprevention. Angioprevention can be proposed at
attacker. So, antibodies are then not formed. A rand- four levels; first for the healthy people, 2nd for popula-
omized clinical trial was conducted to investigate effi- tion at enhanced risk of tumor, 3rd for preneoplastic
cacy of denosumab, a completely human monoclonal disease and 4th for prevention of cancer relapse. There
antibody against receptor activator of nuclear factor κ are numerous achievements in prevention of cancer
B (RANK) ligand, in comparison with zoledronic acid in that reveal medical possibility and levels of interference,
the prevention of skeletal-related events in breast can- from no to slight to strong clinician participation. To
cers individuals with bone metastases. Denosumab was evade toxicity whereas maintaining effectiveness, angio-
found better as compared to zoledronic acid in prevent- prevention desires to attain a level of angiogenesis pre-
ing or delaying the SREs in breast cancer patients with vention that is not extremely oppressive, such that hale
bone metastasis. It is demonstrated that denosumab is and hearty vascular activity is maintained. These drugs
possible therapeutic alternative for individual with bone block angiogenesis. In the absence of blood supply to
metastases [257]. cancer cells, they cannot develop and die. Various drugs
are under investigation for the management of metastatic
Immunotherapy breast cancer. In initial stage of breast cancer, they are
It utilizes the immune system of the body to fight against also investigate in the neoadjuvant (before surgery) set-
the cancer cells [258]. Cancer vaccine is one of its exam- ting [261]. Antiangiogenic treatment in breast cancer
ples. Parts of cancer cells or cancer cells are utilized presents important promise, and numerous continuing
for formation of vaccines. These cells excite the body’s investigations are trying to better describe the best man-
immune system to assist assault and destroy cancer cells agement settings and mediator assortment. For patients
[259]. Immunotherapy has turn into a significant constit- with estrogen receptor positive aliment, researches rec-
uent in the management of breast cancer. HER2 targeted ommend a relationship among resistance of endocrine
treatment are at the present an important part of HER2 and cancer dependence on angiogenic networks, sug-
over expressing breast tumor therapy. Trastuzumab, with gesting a possible curative advantage in mixing endo-
the new current accompaniments of pertuzumab and crine treatment with antiVEGF mediator. Findings from
TDM1, encompass considerably superior breast cancer randomized clinical studies emphasize the multiplicity
prediction. With various Federal Drug and Administra- in reaction to antiVEGF treatment and recommend the
tion recommended antibody treatments used in together requirement for better choice of patient subsets further
the adjuvant and metastatic settings, development pro- to be expected to advantage from these therapies. The
gresses to be done in the area of immunotherapies. recognition of biomarkers for therapy response is solitary
Current achievements in targeted therapies, vigorous part of deep attention, though mainly study to date has
particular immunotherapy, grasp assure for continuous become unsuccessful to discover a relationship linking
success in general endurance within the adjuvant setting. cancer-associated markers including cancer mutations
The extremely precise and targeted strategy of vaccine and EGF expression and scientific response.
therapy not simply avoids the adverse effects of recent
standard of care therapies, active and passive immu- Surveillance and follow up
notherapies including ipilimumab; however presents A regular assessment of the important in print literature
remedial strategy beyond now the HER2-overexpressing conducted by de Bock et al. [262], revealed that 40% of
individuals. Even though vaccines for breast cancers have recurring cancers are identified in asymptomatic individ-
been mainly ineffective in precedent clinical studies, the uals during routine visits. This information intensifies the
most of these studies conducted in the location of late- significance of surveillance and follow-up. Clinical inves-
stage metastatic illness, adverse surroundings for agents tigation such as history and physical examination is sug-
intended to stop, as different to manage, disease. With gested each 4–6 months for 5 years, after that each year
present clinical studies conducted on the adjuvant set- with annual mammography. Female on tamoxifen should
tings, immunogenicity is at the present indicating asso- go through a yearly gynecologic evaluation if the uterus
ciation with medical response. exists. Female who suffers from ovarian failure secondary
to management or on an aromatase inhibitor should have
Anti–angiogenesis drugs checking of bone fitness with a bone mineral thickness
Angiogenesis and inflammation are host-depend- determination at the start and sometimes subsequently.
ent manifestations of tumors that can be targeted Women should also be advised to adopt variable risk
factors, including lessening alcohol use, reducing BMI Publisher’s Note

and enhancing physical activity. Springer Nature remains neutral with regard to jurisdictional claims in pub-
lished maps and institutional affiliations.
Conclusion Received: 15 July 2017 Accepted: 22 September 2017

The increase of information on the pathophysiologic
mechanisms of breast cancer has brought extensive
development in the figure of biomolecular markers. In
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