Male breast cancer (MBC) is a
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
in males that originates in their
breast
The breast is one of two prominences located on the upper ventral region of a primate's torso. Both females and males develop breasts from the same embryological tissues.
In females, it serves as the mammary gland, which produces and secret ...
s. Males account for less than 1% of new breast cancers with about 20,000 new cases being diagnosed
worldwide every year.
Its
incidence rates in males vs. females are, respectively, 0.4 and 66.7 per 100,000 person-years (person-years is the number of new cases divided by the product of the relevant population's size multiplied by the average number of years of observation, i.e. new cases ÷
opulation × years. The worldwide incidences of male as well as female breast cancers have been increasing over the last few decades.
Currently, one of every 800 men are estimated to develop this cancer during their lifetimes.
Because it has a far lower incidence in males and because large-scale breast cancer studies have routinely excluded males, current knowledge of male breast cancer is far less than female breast cancer and often rests on small, retrospective, single-center studies.
Consequently, the majority of strategies for evaluating and treating MBC have been adopted from those used for female breast cancer.
However, MBC appears to have some features that warrant clinical approaches differing from those for female breast cancer.
Features of male breast cancers that differ from those in females include variations in their presentations, associations with other diseases, associations with non-medical predisposing conditions, expressions of key breast cancer-related hormones, causes (including frequency and forms of genetic alterations), tumor types, and treatments.
Presentation, diagnosis and treatment of breast cancer in females
The handling of MBC has typically followed many of the same protocols established for female breast cancer. Female breast cancer most often presents as a mass found on routine screening
mammography
Mammography (also called mastography) is the process of using low-energy X-rays (usually around 30 kVp) to examine the human breast for diagnosis and screening. The goal of mammography is the early detection of breast cancer, typically through d ...
or self-examination. It may have attracted attention by its size, tenderness, painfulness, or, less commonly,
nipple
The nipple is a raised region of tissue on the surface of the breast from which, in females, milk leaves the breast through the lactiferous ducts to feed an infant. The milk can flow through the nipple passively or it can be ejected by smooth mu ...
discharge (which may be bloody), nipple retraction, breast swelling, or appearance of a skin lesion such as an ulcer.
The
physical examination
In a physical examination, medical examination, or clinical examination, a medical practitioner examines a patient for any possible medical signs or symptoms of a medical condition. It generally consists of a series of questions about the patien ...
of these individuals focuses on measuring the size of their lumps and checking other sites, particularly the
lymph node
A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that inclu ...
s in the armpit nearest the tumor, for enlargements or masses that may indicate the tumor has
metastasized
Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...
. At this time or later, depending on further findings such as results of a biopsy, the women may be evaluated by medical imaging techniques such as
ultrasonography
Ultrasound is sound waves with frequencies higher than the upper audible limit of human hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hear it. This limit varies fr ...
,
mammography
Mammography (also called mastography) is the process of using low-energy X-rays (usually around 30 kVp) to examine the human breast for diagnosis and screening. The goal of mammography is the early detection of breast cancer, typically through d ...
,
CT scans,
magnetic resonance imaging
Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio wave ...
,
positron-emission tomography
Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, ...
,
scintimammography
Scintimammography is a type of breast imaging test that is used to detect cancer cells in the breasts of some women who have had abnormal mammograms, or for those who have dense breast tissue, post-operative scar tissue or breast implants.
Scint ...
, and/or
single-photon emission computed tomography
Single-photon emission computed tomography (SPECT, or less commonly, SPET) is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera (that is, ...
to determine the extent of the primary tumor and presence of nearby lymph node and/or distant tissue lesions that may be metastases.
Before or after these initial studies, tissues from the lump are obtained by needle biopsy (sampling with a
surgical needle), incisional biopsy (surgical sampling of a part of the tumor), or excisional biopsy (surgical removal of the entire tumor). The recovered tissue is examined for its microscopic
histopathology
Histopathology (compound of three Greek words: ''histos'' "tissue", πάθος ''pathos'' "suffering", and -λογία '' -logia'' "study of") refers to the microscopic examination of tissue in order to study the manifestations of disease. Spe ...
and presence of tumor cells that express the
estrogen receptor
Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen ( 17β-estradiol). Two classes of ER exist: nuclear estrogen receptors (ERα and ERβ), which are members of the ...
,
progesterone receptor
The progesterone receptor (PR), also known as NR3C3 or nuclear receptor subfamily 3, group C, member 3, is a protein found inside cells. It is activated by the steroid hormone progesterone.
In humans, PR is encoded by a single ''PGR'' gene resid ...
, and
HER2/neu
Receptor tyrosine-protein kinase erbB-2 is a protein that in humans is encoded by the ''ERBB2'' gene. ERBB is abbreviated from erythroblastic oncogene B, a gene originally isolated from the avian genome. The human protein is also frequently refer ...
receptor. The tumor may also be examined for cells that express the
androgen receptor
The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone in th ...
and various gene
mutations
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
or other types of gene alterations that are known to be associated with and may contributor to the development and/or progression of breast cancer.
Biopsy of the
sentinel lymph node
The sentinel lymph node is the hypothetical first lymph node or group of nodes draining a cancer. In case of established cancerous dissemination it is postulated that the sentinel lymph nodes are the target organs primarily reached by metastasiz ...
(i.e. armpit lymph node closest to the tumor) or multiple other lymph nodes located in this armpit as well as any suspicious and accessible lesion may also be taken.
(Sentinel lymph node biopsy is preferred over broad dissection of the armpit lymph nodes for detecting local lymph node metastases.
) Based on the findings of these examinations, the tumor, if considered cancerous, is further defined based on its: a)
clinical stage typically using the
TNM staging system
The TNM Classification of Malignant Tumors (TNM) is a globally recognised standard for classifying the extent of spread of cancer. It is a classification system of the anatomical extent of tumor cancers. It has gained wide international acceptance ...
(i.e. scoring (T)umor size, (N)umber of armpit lymph nodes near the primary tumor with metastases, and (M)etastases in distant tissues); b)
grade
Grade most commonly refers to:
* Grade (education), a measurement of a student's performance
* Grade, the number of the year a student has reached in a given educational stage
* Grade (slope), the steepness of a slope
Grade or grading may also ref ...
using the Nottingham system (grades 1, 2, and 3 indicate the tumor cells look progressively less like, and therefore are potentially more aggressive than, the normal tissue cells from which they arose); and c)
histopathology
Histopathology (compound of three Greek words: ''histos'' "tissue", πάθος ''pathos'' "suffering", and -λογία '' -logia'' "study of") refers to the microscopic examination of tissue in order to study the manifestations of disease. Spe ...
(i.e. either ''in situ'' or invasive, i.e. cancer cells confined to their tissue of origin or invading adjacent tissue(s), respectively). The histopathology of these tumor is also critical for classifying the
breast cancer's type. Depending on their cancers' severity predicted by these analyses, female breast cancer patients are treated with
surgical removal,
radiotherapy
Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radia ...
,
chemotherapy
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
,
hormonal therapy
Hormone therapy or hormonal therapy is the use of hormones in medical treatment. Treatment with hormone antagonists may also be referred to as hormonal therapy or antihormone therapy. The most general classes of hormone therapy are hormonal therap ...
, and/or
immunotherapy
Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...
(i.e. drugs activating or suppressing an individual's
immune system
The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
).
Differences between MBC and female breast cancer
The following lists medically important breast cancer features that differ between males and females:
* Presentation: Due to men's smaller breast sizes, their breast tumors may become palpable and cause symptoms earlier those than in females. Nonetheless, males tend to lack awareness of breast cancer, may have
gynecomastia
Gynecomastia (also spelled gynaecomastia) is the abnormal non-cancerous enlargement of one or both breasts in males due to the growth of breast tissue as a result of a hormone imbalance between estrogens and androgens. Updated by Brent Wisse (1 ...
masking their breast tumors, and may delay seeking medical attention. These differences appear to underlie findings that the diagnosis of breast cancer is made later in males than females (average age 67 vs. 63 years old, respectively).
Studies have reported that males more often than females present with breast cancers that have spread to nearby axillary lymph nodes and appear more aggressive based on their microscopic histopathology.
However, a large study by the
Surveillance, Epidemiology, and End Results
The Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute (NCI) is a source of epidemiologic information on the incidence and survival rates of cancer in the United States.
The Program
SEER collects and pub ...
program of the
National Institutes of Health
The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
ranked breast cancer severity based on their TNM stage. The study reported that the percentage of cases presenting with purely local disease (i.e. no metastases) was 63.1% in males and 45.4% in females; with spread to local lymph nodes was 29.1% in males and 43.6% in females; and with distant metastases was 5.7% in males and 8.1% in females (2.1% of males and 2.9% of females were not staged).
* Development of contralateral breast cancers: Men with breast cancer have an
absolute risk Absolute risk (or AR) is the probability or chance of an event. It is usually used for the number of events (such as a disease) that occurred in a group, divided by the number of people in that group.
Absolute risk is one of the most understandable ...
of presenting with a second cancer in their other breast of 1.75, i.e. they have a 75% increase of developing a contralateral breast cancer over their lifetimes compared to men who develop a breast cancer without having had a prior breast cancer.
Female breast cancer is likewise associated with the development of contralateral breast cancer,
with one large study finding the five-year cumulative incidence of developing a contralateral breast cancer of 2.5%.
The
relative risk
The relative risk (RR) or risk ratio is the ratio of the probability of an outcome in an exposed group to the probability of an outcome in an unexposed group. Together with risk difference and odds ratio, relative risk measures the association bet ...
of developing a contralateral breast cancer following mastectomy of the involved breast in men versus the probability of developing breast cancer in men without a history of breast cancer is significantly higher than the relative risk in women.
In order to prevent cancer from developing later in their contralateral breasts, women have had prophylactic mastectomy of their uninvolved breasts at the time of their diseased breast's mastectomy. However, increasing evidence in some studies suggest prophylactic mastectomy provides no survival advantage and is associated with increased costs and higher complication rates.
The rates of female vs. male contralateral breast cancer and the value of prophylactic mastectomy of the uninvolved breast in males, perhaps because of their rarity compared to females, is unclear. However, breast cancers associated with ''
BRCA1
Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the ''BRCA1'' () gene. Orthologs are common in other vertebrate species, whereas invertebrate genomes may encode a more distantly related gene. ''BRCA1'' is a h ...
'' or ''
BRCA2
''BRCA2'' and BRCA2 () are a human gene and its protein product, respectively. The official symbol (BRCA2, italic for the gene, nonitalic for the protein) and the official name (originally breast cancer 2; currently BRCA2, DNA repair associated) ...
''
gene mutations (see below section on "Gene mutations") are widely considered to be the strongest indication for contralateral prophylactic mastectomy in both male and female breast cancers.
* Physical activity: Studies have reported 1) lower rates of breast cancer (i.e. by 20-25%) in men with an employment history involving high levels of physical activity and 2) higher rates of breast cancer in men with an employment history involving low levels of physical activity. Changes in the fat tissue microenvironment in the male breast as a result of physical activity may contribute to these differences.
The level of physical activity has similar effects on the development of female physical activity.
However, most studies show that the protective effect in female breast cancer is a 13% decreased risk in high versus low physical activity groups and is limited to postmenopausal women.
It is not clear that the higher benefit of physical activity in MBC (20 to 25%) is significantly greater than the 12% benefit seen in female breast cancer.
*Additional risk factors: Radiation exposure to the chest or entire body is clearly associated with increased rates of MBC.
For example, men treated with radiotherapy to the chest for thymus gland enlargement or gynecomastia have an increased rate of later developing breast cancer;
men
and women
treated with
radiotherapy
Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radia ...
for breast cancers have increased rates of developing contralateral breast cancer; and male
and female
survivors of the atomic bomb attacks in Japan (1945) had increased rates of developing breast cancer in proportion to their increasing levels of radiation exposure. Men with a history of high alcohol consumption and men with occupations entailing long-term exposure to high temperatures (e.g. such as to blast furnaces, steel works, and rolling mills, i.e. mills processing metals), petrol emissions, or exhaust emissions have had, in some studies, increased risks of developing breast cancer.
High alcohol consumption is also a risk factor for breast cancer in females.
* Expression of key receptors: The
estrogen
Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...
(ER),
progesterone
Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the m ...
(PR),
androgen
An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This inc ...
(AR), and
HER2/neu
Receptor tyrosine-protein kinase erbB-2 is a protein that in humans is encoded by the ''ERBB2'' gene. ERBB is abbreviated from erythroblastic oncogene B, a gene originally isolated from the avian genome. The human protein is also frequently refer ...
receptors
Receptor may refer to:
*Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a n ...
are expressed by breast cancer cells and when active elicit various potentially pro-cancerous responses (e.g. excessive growth) in their parent cells. ER, PR, and AR are activated by estrogens, progesterone, and androgens, respectively,
while the HER2/neu receptor has no known hormone-like activators but is active when attached to other members of the
ErbB
The ErbB family of proteins contains four receptor tyrosine kinases, structurally related to the epidermal growth factor receptor (EGFR), its first discovered member. In humans, the family includes Her1 (EGFR, ErbB1), Her2 (Neu, ErbB2), Her3 (Er ...
family within the same cell, when overproduced, or when containing certain mutations.
The percentage of cases in which breast cancer cells express an ER is 99% of males and 77% of females, the PR is 82% of males and 64% of females, an AR is 97% of males and 77% of females; and the HER2/neu is 9% of males and 11% of females. About 0.3% of males and 11% of females have
triple-negative breast cancer
Triple-negative breast cancer (TNBC) is any breast cancer that lacks or show low levels of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) overexpression and/or gene amplification (i.e. the t ...
, i.e. do not have breast cancer cells that express ER, PR, and HER2/neu receptors and consequently are not amenable to treatment with inhibitors of these receptors. On the other hand, the extremely high rate of estrogen receptor expression in MBC has led to commonly treating these men with a
selective estrogen receptor modulator
Selective estrogen receptor modulators (SERMs), also known as estrogen receptor agonist/antagonists (ERAAs), are a class of drugs that act on the estrogen receptor (ER). A characteristic that distinguishes these substances from pure ER agonists a ...
,
tamoxifen
Tamoxifen, sold under the brand name Nolvadex among others, is a selective estrogen receptor modulator used to prevent breast cancer in women and treat breast cancer in women and men. It is also being studied for other types of cancer. It has b ...
.
Tamoxifen acts indirectly to inhibit ER signaling in breast cancer cells.
* Associations with other diseases and conditions:
Klinefelter syndrome
Klinefelter syndrome (KS), also known as 47,XXY, is an aneuploid genetic condition where a male has an additional copy of the X chromosome. The primary features are infertility and small, poorly functioning testicles. Usually, symptoms are su ...
is a rare genetic disease in which males have inherited an extra
X chromosome
The X chromosome is one of the two sex-determining chromosomes (allosomes) in many organisms, including mammals (the other is the Y chromosome), and is found in both males and females. It is a part of the XY sex-determination system and XO sex-d ...
. Men with this disease have
gynecomastia
Gynecomastia (also spelled gynaecomastia) is the abnormal non-cancerous enlargement of one or both breasts in males due to the growth of breast tissue as a result of a hormone imbalance between estrogens and androgens. Updated by Brent Wisse (1 ...
, obesity,
testicular dysgenesis
Gonadal dysgenesis is classified as any congenital developmental disorder of the reproductive system
in the male or female. It is the atypical development of the gonads in an embryo,
with reproductive tissue replaced with functionless, fibrous ti ...
(i.e. failure to develop functional
testes
A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testoster ...
), and various other abnormalities including a 20 to 50-fold increased risk of developing MBC. It is thought that this increased risk is primarily due to their low
androgen
An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This inc ...
levels, high
gonadotrophin
Gonadotropins are glycoprotein hormones secreted by gonadotropic cells of the anterior pituitary of vertebrates. This family includes the mammalian hormones follicle-stimulating hormone (FSH) and luteinizing hormone (LH), the placental/chorionic ...
s levels, and consequently high estrogen levels relative to androgen levels.
Other states in which males have excessive estrogen relative to androgen levels and increased rates of developing MBC include liver
cirrhosis
Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue repai ...
(females with liver cirrhosis do not have an increased incidence of breast cancer), testicular dysfunction (due to, e.g.
undescended testes
Cryptorchidism, also known as undescended testis, is the failure of one or both testes to descend into the scrotum. The word is from Greek language, Greek () 'hidden' and () 'testicle'. It is the most common birth defect of the male genital tra ...
, congenital
inguinal hernia
An inguinal hernia is a hernia (protrusion) of abdominal-cavity contents through the inguinal canal. Symptoms, which may include pain or discomfort especially with or following coughing, exercise, or bowel movements, are absent in about a third ...
,
orchitis
Orchitis is inflammation of the testes. It can also involve swelling, pains and frequent infection, particularly of the epididymis, as in epididymitis. The term is from the Ancient Greek ὄρχις meaning "testicle"; same root as ''orchid''.
S ...
, i.e. inflammation of the testes caused by, e.g.
mumps
MUMPS ("Massachusetts General Hospital Utility Multi-Programming System"), or M, is an imperative, high-level programming language with an integrated transaction processing key–value database. It was originally developed at Massachusetts Gener ...
or testicular malignancies), and consumption of hormonal drugs for, e.g.
gender reassignment therapy
Sex reassignment therapy or medical transition is the medical aspect of gender transition, that is, modifying one's sex characteristics to better suit one's gender identity. It can consist of hormone therapy to alter secondary sex characterist ...
.
(One study reported a 46-fold increased rate of MBC in trans women, i.e. gender reassignment from male to female.) A large study found that diabetes is associated with an increased risk of developing breast cancer with men having a slightly higher but significant risk than women (20.1% of all men vs. 16.5% of all women).
Earlier studies regarded gynecomastia as a risk factor for MBC but more recent work suggests that this has not been established.
Cases of MBC occur in individuals with three rare inherited genetic disorders, the
Li-Fraumeni syndrome,
Lynch syndrome
Hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome is an autosomal dominant genetic condition that is associated with a high risk of colon cancer as well as other cancers including endometrial cancer (second most common), ovary, ...
, and
Cowden syndrome
Cowden syndrome (also known as Cowden's disease and multiple hamartoma syndrome) is an autosomal dominant inherited condition characterized by benign overgrowths called hamartomas as well as an increased lifetime risk of breast, thyroid, uterine, ...
, although the
odds ratio
An odds ratio (OR) is a statistic that quantifies the strength of the association between two events, A and B. The odds ratio is defined as the ratio of the odds of A in the presence of B and the odds of A in the absence of B, or equivalently (due ...
s (i.e. statistical strength) of these associations is not yet known.
In one study of 58 MBC cases, 11 had one or two other malignancies; the malignancies included prostate cancer (4 cases), prostate cancer in a man with Klinefelter’s syndrome (1 case), oral cavity cancer plus prostate cancer (1 case)), and melanoma plus colon cancer (1 case).
* Types of breast cancer: Before puberty, male and female mammary tissues consist primarily of
ducts connected to poorly developed
mammary lobules, i.e. sacs that are connected to the ducts and will produce milk after pregnancy. Following puberty, females but not males have hormone-induced growth in these lobules.
Consequently, adult males have far less lobular tissue than adult females
and present with beast carcinomas that arise from lobules in ~1% of all cases and ducts in 89% of all cases; these values in women are 8% and 73%, respectively.
The commonest histopathology-defined type of MBC is, as it is in females,
invasive ductal carcinoma
Invasive carcinoma of no special type (NST) also known as invasive ductal carcinoma or ductal NOS and previously known as invasive ductal carcinoma, not otherwise specified (NOS) is a group of breast cancers that do not have the "specific different ...
(also termed invasive carcinoma of no special type).
The other histopathologically-defined types of MBC in descending order of frequency include
ductal carcinoma in situ
Ductal carcinoma in situ (DCIS), also known as intraductal carcinoma, is a pre-cancerous or non-invasive cancerous lesion of the breast. DCIS is classified as Stage 0. It rarely produces symptoms or a breast lump one can feel, typically being d ...
,
papillary carcinomas of the breast (occurs in each of its four subtypes, ''in situ'', encapsulated, solid-paapillary, and invasive papillary carcinoma),
medullary breast carcinoma,
mucinous carcinoma
A mucinous neoplasm (also called colloid neoplasm) is an abnormal and excessive growth of tissue (neoplasia) with associated mucin (a fluid that sometimes resembles thyroid colloid). It arises from epithelial cells that line certain internal orga ...
,
inflammatory carcinoma,
phyllodes tumor
Phyllodes tumors (from Greek: ''phullon'' leaf), also cystosarcoma phyllodes, cystosarcoma phylloides and phylloides tumor, are typically large, fast-growing masses that form from the periductal stromal cells of the breast. They account for less th ...
,
leiomyosarcoma
Leiomyosarcoma is a malignant (cancerous) smooth muscle tumor. A benign tumor originating from the same tissue is termed leiomyoma. While leiomyosarcomas are not thought to arise from leiomyomas, some leiomyoma variants' classification is evolv ...
of the breast,
Paget's disease of the breast
Paget's disease of the breast is a type of cancer that outwardly may have the appearance of eczema, with skin changes involving the nipple of the breast. The condition is an uncommon disease accounting for 1 to 4.3% of all breast cancers and was ...
, and
invasive lobular carcinoma
Invasive lobular carcinoma (ILC) is breast cancer arising from the lobules of the mammary glands. It accounts for 5–10% of invasive breast cancer. Rare cases of this carcinoma have been diagnosed in men (see male breast cancer).
Types
The his ...
.
Mammary secretory carcinoma
Mammary secretory carcinoma (MSC), also termed secretory carcinoma of the breast, is a rare form of the breast cancers. MSC usually affects women but in a significant percentage of cases also occurs in men and children. Indeed, McDvitt and Stewart ...
and
invasive cribriform carcinoma of the breast
Invasive cribriform carcinoma of the breast (ICCB), also termed invasive cribriform carcinoma, is a rare type of breast cancer that accounts for 0.3% to 0.6% of all carcinomas (i.e. cancers that develop from epithelial cells) in the breast. It o ...
which in recent studies have accounted for more than 3% and 1.7%, respectively, of MBC cases, can be added to near the top of this list whereas
tubular carcinoma of the breast, a subtype of the invasive ductal carcinomas, occurs but is extremely rare in men.
Female breast cancers have a far greater number of types (see
breast cancer types) than those reported for men. This may reflect the rarity of many female breast types combined with the rarity of male breast cancer.
* Gene mutations: Two inherited gene mutations critically associated with the development and/or progression of breast cancer occur in the tumor cells of MBC and female breast cancer but with different frequencies: ''
BRCA2
''BRCA2'' and BRCA2 () are a human gene and its protein product, respectively. The official symbol (BRCA2, italic for the gene, nonitalic for the protein) and the official name (originally breast cancer 2; currently BRCA2, DNA repair associated) ...
'' mutations occur in 12% of males and 5% of females while ''
BRCA1
Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the ''BRCA1'' () gene. Orthologs are common in other vertebrate species, whereas invertebrate genomes may encode a more distantly related gene. ''BRCA1'' is a h ...
'' mutations occur in 1% of males and 5-10% of females.
These mutations are the two most frequent causes of the
hereditary breast–ovarian cancer syndrome
Hereditary breast–ovarian cancer syndromes (HBOC) are cancer syndromes that produce higher than normal levels of breast cancer, ovarian cancer and additional cancers in genetically related families (either one individual had both, or several in ...
, a syndrome associated with increased risks of developing not only breast cancer but also ovary cancer, prostate cancer, and less commonly pancreatic cancer and
melanoma
Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...
.
Mutations in other genes such as ''
CHEK2
CHEK2 (Checkpoint kinase 2) is a tumor suppressor gene that encodes the protein CHK2, a serine-threonine kinase. CHK2 is involved in DNA repair, cell cycle arrest or apoptosis in response to DNA damage. Mutations to the CHEK2 gene have been linked ...
,
PALB2
Partner and localizer of BRCA2, also known as PALB2 or FANCN, is a protein which in humans is encoded by the ''PALB2'' gene.
Function
This gene encodes a protein that functions in genome maintenance ( double strand break repair). This prote ...
,
PTEN,
ATM''
and ''
RAD51L3
DNA repair protein RAD51 homolog 4 is a protein that in humans is encoded by the ''RAD51L3'' gene.
Function
The protein encoded by this gene is a member of the RAD51 protein family. RAD51 family members are highly similar to bacterial RecA and ...
'' (also termed ''RAD51D'')
have been reported to occur uncommonly in, and may confer an increased risk of developing, MBC. These genes are uncommon causes of the hereditary breast-ovarian syndrome but for the most part are associated with breast but not the other cancers in men. Mutations in the latter genes also occur in female breast cancer and are associated with ovarian as well as breast cancer. The rates of these mutations in male vs. female breast cancer have not been defined.
Breast cancer in the Cowden syndrome is associated with ''PTEN'' gene mutations, in the Li-Fraumeni syndrome with ''
tumor protein P53'' gene mutations,
and in the Lynch syndrome with mutations in any of the four
DNA mismatch repair
DNA mismatch repair (MMR) is a system for recognizing and repairing erroneous insertion, deletion, and mis-incorporation of nucleobase, bases that can arise during DNA replication and Genetic recombination, recombination, as well as DNA repair, r ...
genes (''MLH1, MSH2, MSH6'', ''PMS2''), or the ''
EpCAM
Epithelial cell adhesion molecule (EpCAM), also known as CD326 among other names, is a transmembrane glycoprotein mediating Ca2+-independent homotypic cell–cell adhesion in epithelia. EpCAM is also involved in cell signaling, migration, prol ...
'' gene.
The relative risks of men vs. women with these inherited syndromes developing breast cancer are unclear.
Since men without a history of breast cancer who carry a mutation in a ''BRCA2'' or ''BRCA1'' gene have increased rates of developing prostate cancer,
screening for prostate cancer in men with beast cancer who are 45 years or older and carry a ''BRCA2'' gene mutation is strongly recommended and should be considered for men with a ''BRCA1'' gene mutation. The
National Comprehensive Cancer Network
National Comprehensive Cancer Network (NCCN) is an alliance of 32 cancer centers in the United States, most of which are designated by the National Cancer Institute (one of the U.S. National Institutes of Health) as comprehensive cancer centers. It ...
recommends self-breast examination starting at age 35 for men with mutations in either ''BRCA'' gene.
* Treatment and prognosis: Similar to breast cancer tumors in women, MBC tumors are treated by surgical removal, radiotherapy, chemotherapy, immunotheapy, and/or hormonal therapy. However, there are key differences in these treatments between the two sexes. The most common surgical treatment for MBC tumors has been
total mastectomy with
breast-conserving surgery
Breast-conserving surgery (BCS) refers to an operation that aims to remove breast cancer while avoiding a mastectomy. Different forms of this operation include: lumpectomy (tylectomy), wide local excision, segmental resection, and quadrantectom ...
being performed in a much smaller proportion of males than females. This difference may be due to men generally having smaller breasts, tumors more often located beneath the
areola
The human areola (''areola mammae'', or ) is the pigmented area on the breast around the nipple. Areola, more generally, is a small circular area on the body with a different histology from the surrounding tissue, or other small circular ar ...
, tumors more often involving nipples and/or skin, and tumors more often having smaller and narrower
resection margin
A resection margin or surgical margin is the margin of apparently non-tumorous tissue around a tumor that has been surgically removed, called " resected", in surgical oncology. The resection is an attempt to remove a cancer tumor so that no portio ...
s than women. These conditions increase the probability that breast-conserving surgery will leave some tumor cells behind and therefore increase the rate of tumor recurrences. Furthermore,
sentinel lymph node
The sentinel lymph node is the hypothetical first lymph node or group of nodes draining a cancer. In case of established cancerous dissemination it is postulated that the sentinel lymph nodes are the target organs primarily reached by metastasiz ...
biopsies (i.e. biopsies of the armpit lymph node nearest to the tumor) pose challenges because there are anatomical differences in lymph node drainages around the breasts between women and men that can lead to misidentifications of sentinel lymph nodes in men. In spite of these reservations, a recent review of 14,061 MBC cases found no statistically significant difference in the
overall survival rates of men treated with mastectomy vs. breast-conserving surgery at 5 years (49.4% vs. 54.7, respectively) and 10 years (19.7 vs. 25.1%, respectively). The study also found that: a) men treated with adjuvant radiotherapy (i.e. radiotherapy in addition to other treatments) had significantly higher 5 year overall survival rates than men not treated with radiation therapy (59.4% v.s. 44.5%, respectively); b) Tamoxifen therapy improved overall survival rates compared to treatments not using tamoxifen at 5 years (81.7 vs. 71.4, respectively) and 10 years (57.9 vs. 50.4, respectively); c) Tamoxifen therapy improved 5 year overall survival rates compared to therapy with
aromatase inhibitors
Aromatase inhibitors (AIs) are a class of drugs used in the treatment of breast cancer in postmenopausal women and in men, and gynecomastia in men. They may also be used off-label to reduce estrogen conversion when supplementing testosterone exog ...
(i.e. medicines that block the production of estrogens); and d) therapy with an aromatase inhibitor plus a
GNRH agonist
A gonadotropin-releasing hormone agonist (GnRH agonist) is a type of medication which affects gonadotropins and sex hormones. They are used for a variety of indications including in fertility medicine and to lower sex hormone levels in the treat ...
(i.e. medicines that indirectly inhibit production of estrogens, progesterone, and androgens
) improved the 5 year overall survival rate over an aromatase inhibitor without a GnRH agonist;
Tamoxifen is routinely and very commonly prescribed for treating all stages of MBC. Indeed, studies suggest that the first-line treatment of choice for metastatic male (but not female) breast cancer is tamoxifen with chemotherapy being reserved for MBC cases that are estrogen receptor-negative or become unresponsive to tamoxifen plus highly symptomatic.
Other studies have found that the prognosis of MBC, similar to female breast cancer: depends on their cancer's TNM stage; that stage for stage, the prognoses of MBC appears similar to that in female breast cancer; and that MBC has a somewhat lower 5-year overall survival rate than female breast cancer (82.8% vs. 88.5%, respectively).
However, men with breast cancer tend to have additional comorbidities including serious neoplasms and are more likely to die from other causes compared to women with breast cancer. It is suggested that
disease-specific survival rate (i.e. percentage of individuals who have not died from breast cancer) would be a more accurate measure of MBC treatment efficacies, prognoses, and survivals than overall survival rates (i.e. the percentage of all individuals who are alive at an indicated time after initial treatment regardless of the cause of death) and should be reported in future studies on MBC.
References
TNM
External links
{{Breast cancer types
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Breast cancer
Hereditary cancers
Rare cancers