Male breast cancer
Encyclopedia
Male breast cancer is a relatively rare cancer
in men that originates from the breast
. As it presents a similar pathology
as female breast cancer
, assessment and treatment relies on experiences and guidelines that have been developed in female patients. The optimal treatment is currently not known.
exposure, exposure to female hormones (estrogen
), and genetic factors. High estrogen exposure may occur by medications, obesity
, or liver disease
, and genetic links include a high prevalence of female breast cancer in close relatives. Chronic alcoholism
has been linked to male breast cancer. The highest risk for male breast cancer is carried by men with Klinefelter syndrome. Male BRCA mutation
carriers are thought to be at higher risk for breast cancer.
have been described, lobular carcinoma in situ has not been seen in men. Breast cancer in men spreads via lymphatics and blood stream like female breast cancer. Accordingly, the TNM staging system for breast cancer is the same for men and women.
Size of the lesion and lymph node involvement determine prognosis; thus small lesions without lymph node involvement have the best prognosis. Estrogen receptor
and progesterone receptor
status and HER2/neu gene amplification need to be reported as they may affect treatment options. About 85% of all male breast cancers are estrogen receptor–positive, and 70% are progesterone receptor–positive.
discharge, nipple retraction. swelling of the breast, or a skin lesion such as an ulcer. Ultrasound and mammography
may be used for its further definition. The lump can be examined either by a needle biopsy where a thin needle is placed into the lump to extract some tissue or by an excisional biopsy where under local anesthesia a small skin cut is made and the lump is removed. Not all palpable lesions in the male breast are cancerous, for instance a biopsy may reveal a benign fibroadenoma
. In a larger study from Finland the average size of a male breast cancer lesion was 1.8 cm. Beside the histologic examination
estrogen and progesterone receptor studies are performed. Further, the HER2 test is used to check for a growth factor protein. Its activity can be increased in active cancer cells and helps determine if monoclonal antibody therapy (i.e. Trastuzumab
) may be useful.
Male breast cancer can recur locally after therapy, or can become metastatic.
Stage IIA: One of the following applies:
T0 or T1, N1 (but not N1mi), M0: The tumor is 2 cm or less across (or is not found) (T1 or T0) and either:
It has spread to 1 to 3 axillary lymph nodes (N1a), but not to distant sites (M0), OR
Tiny amounts of cancer are found in internal mammary lymph nodes on sentinel lymph node biopsy (N1b), but not in distant sites (M0), OR.
It has spread to 1 to 3 axillary lymph nodes, and tiny amounts of cancer are found in internal mammary lymph nodes on sentinel lymph node biopsy (N1c), but not to distant sites (M0).
OR
T2, N0, M0: The tumor is larger than 2 cm across and less than 5 cm (T2), but it hasn't spread to the lymph nodes (N0) or to distant sites (M0).
Stage IIB: One of the following applies:
T2, N1, M0: The tumor is larger than 2 cm and less than 5 cm across (T2). It has spread to 1 to 3 axillary lymph nodes and/or tiny amounts of cancer are found in internal mammary lymph nodes on sentinel lymph node biopsy (N1). It has not spread to distant sites (M0).
OR
T3, N0, M0: The tumor is larger than 5 cm across but does not grow into the chest wall or skin (T3). It has not spread to lymph nodes (N0) or to distant sites (M0).
may mask the condition. The diagnosis is made later in men—at age 67 on average—than in women with their average at 63. Lesions are less contained in men as they do not have to travel far to infiltrate skin, nipple, or muscle tissue. Thus, lesions in men tend to be more advanced. Indeed, almost half of male breast cancer patients are stage III or IV. In familial cases, male BRCA2 carriers are at risk, rather than BRCA1 carriers. With the relative infrequency of male breast cancer, randomized studies are lacking.
with axillary dissection or lumpectomy
and radiation therapy with similar treatment results as in women. Also, mastectomy with sentinel lymph node
biopsy is a treatment option. In men with node-negative tumors, adjuvant therapy is applied under the same considerations as in women with node-negative breast cancer. Similarly, with node-positive tumors, men increase survival using the same adjuvants as affected women, namely both chemotherapy plus tamoxifen and other hormonal therapy. There are no controlled studies in men comparing adjuvant options. In the vast majority of men with breast cancer hormone receptor studies are positive, and those situations are typically treated with hormonal therapy.
Locally recurrent disease is treated with surgical excision or radiation therapy combined with chemotherapy. Distant metastases are treated with hormonal therapy, chemotherapy, or a combination of both. Bones can be affected either by metastasis or weakened from hormonal therapy; bisphosphonate
s may be used to counterbalance this process and strengthen bones.
Hormonal options include:
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
in men that originates from the breast
Breast
The breast is the upper ventral region of the torso of a primate, in left and right sides, which in a female contains the mammary gland that secretes milk used to feed infants.Both men and women develop breasts from the same embryological tissues...
. As it presents a similar pathology
Pathology
Pathology is the precise study and diagnosis of disease. The word pathology is from Ancient Greek , pathos, "feeling, suffering"; and , -logia, "the study of". Pathologization, to pathologize, refers to the process of defining a condition or behavior as pathological, e.g. pathological gambling....
as female breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
, assessment and treatment relies on experiences and guidelines that have been developed in female patients. The optimal treatment is currently not known.
Incidence
About one percent of breast cancer develops in males. It is estimated that about 2,140 new cases are diagnosed annually in the US and about 300 in the UK, and the number of annual deaths is about 450 in the US. In a study from India, eight out of 1,200 (0.7%) male cancer diagnoses in a pathology review represented breast cancer. The incidence of breast cancer in men has been increasing. The tumor can occur over a wide age range, but typically appears in men in their sixties and seventies. Known risk factors include radiationRadiation
In physics, radiation is a process in which energetic particles or energetic waves travel through a medium or space. There are two distinct types of radiation; ionizing and non-ionizing...
exposure, exposure to female hormones (estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
), and genetic factors. High estrogen exposure may occur by medications, obesity
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
, or liver disease
Liver disease
Liver disease is a broad term describing any single number of diseases affecting the liver.-Diseases:* Hepatitis, inflammation of the liver, caused mainly by various viruses but also by some poisons , autoimmunity or hereditary conditions...
, and genetic links include a high prevalence of female breast cancer in close relatives. Chronic alcoholism
Alcoholism
Alcoholism is a broad term for problems with alcohol, and is generally used to mean compulsive and uncontrolled consumption of alcoholic beverages, usually to the detriment of the drinker's health, personal relationships, and social standing...
has been linked to male breast cancer. The highest risk for male breast cancer is carried by men with Klinefelter syndrome. Male BRCA mutation
BRCA mutation
A BRCA mutation is a mutation in either of the genes BRCA1 and BRCA2. Harmful mutations in these genes produce a hereditary breast-ovarian cancer syndrome in affected families...
carriers are thought to be at higher risk for breast cancer.
Pathology
As in females, infiltrating ductal carcinoma is the most common type. While intraductal cancer, inflammatory carcinoma, and Paget's disease of the nipplePaget's disease of the breast
Paget's disease of the breast is a malignant condition that outwardly may have the appearance of eczema, with skin changes involving the nipple of the breast....
have been described, lobular carcinoma in situ has not been seen in men. Breast cancer in men spreads via lymphatics and blood stream like female breast cancer. Accordingly, the TNM staging system for breast cancer is the same for men and women.
Size of the lesion and lymph node involvement determine prognosis; thus small lesions without lymph node involvement have the best prognosis. Estrogen receptor
Estrogen receptor
Estrogen receptor refers to a group of receptors that are activated by the hormone 17β-estradiol . Two types of estrogen receptor exist: ER, which is a member of the nuclear hormone family of intracellular receptors, and the estrogen G protein-coupled receptor GPR30 , which is a G protein-coupled...
and progesterone receptor
Progesterone receptor
The progesterone receptor also known as NR3C3 , is an intracellular steroid receptor that specifically binds progesterone...
status and HER2/neu gene amplification need to be reported as they may affect treatment options. About 85% of all male breast cancers are estrogen receptor–positive, and 70% are progesterone receptor–positive.
Diagnosis
Typically self-examination leads to the detection of a lump in the breast which requires further investigation. Other less common symptoms include nippleNipple
In its most general form, a nipple is a structure from which a fluid emanates. More specifically, it is the projection on the breasts or udder of a mammal by which breast milk is delivered to a mother's young. In this sense, it is often called a teat, especially when referring to non-humans, and...
discharge, nipple retraction. swelling of the breast, or a skin lesion such as an ulcer. Ultrasound and mammography
Mammography
Mammography is the process of using low-energy-X-rays to examine the human breast and is used as a diagnostic and a screening tool....
may be used for its further definition. The lump can be examined either by a needle biopsy where a thin needle is placed into the lump to extract some tissue or by an excisional biopsy where under local anesthesia a small skin cut is made and the lump is removed. Not all palpable lesions in the male breast are cancerous, for instance a biopsy may reveal a benign fibroadenoma
Fibroadenoma
Fibroadenomas of the breast, are lumps composed of fibrous and glandular tissue. Because breast cancer can also appear as a lump, doctors may recommend a tissue sample to rule out cancer in older patients...
. In a larger study from Finland the average size of a male breast cancer lesion was 1.8 cm. Beside the histologic examination
Histology
Histology is the study of the microscopic anatomy of cells and tissues of plants and animals. It is performed by examining cells and tissues commonly by sectioning and staining; followed by examination under a light microscope or electron microscope...
estrogen and progesterone receptor studies are performed. Further, the HER2 test is used to check for a growth factor protein. Its activity can be increased in active cancer cells and helps determine if monoclonal antibody therapy (i.e. Trastuzumab
Trastuzumab
Trastuzumab is a monoclonal antibody that interferes with the HER2/neu receptor.The HER receptors are proteins that are embedded in the cell membrane and communicate molecular signals from outside the cell to inside the cell, and turn genes on and off...
) may be useful.
Male breast cancer can recur locally after therapy, or can become metastatic.
Staging
In addition to TNM staging surgical staging for breast cancer is used; it is the same as in female breast cancer and facilitates treatment and analysis.- Stage I refers to invasive breast cancer with the tumor not exceeding 2 cm and absence of lymph node involvement.
- Stage II: Includes stages IIA and IIB
Stage IIA: One of the following applies:
T0 or T1, N1 (but not N1mi), M0: The tumor is 2 cm or less across (or is not found) (T1 or T0) and either:
It has spread to 1 to 3 axillary lymph nodes (N1a), but not to distant sites (M0), OR
Tiny amounts of cancer are found in internal mammary lymph nodes on sentinel lymph node biopsy (N1b), but not in distant sites (M0), OR.
It has spread to 1 to 3 axillary lymph nodes, and tiny amounts of cancer are found in internal mammary lymph nodes on sentinel lymph node biopsy (N1c), but not to distant sites (M0).
OR
T2, N0, M0: The tumor is larger than 2 cm across and less than 5 cm (T2), but it hasn't spread to the lymph nodes (N0) or to distant sites (M0).
Stage IIB: One of the following applies:
T2, N1, M0: The tumor is larger than 2 cm and less than 5 cm across (T2). It has spread to 1 to 3 axillary lymph nodes and/or tiny amounts of cancer are found in internal mammary lymph nodes on sentinel lymph node biopsy (N1). It has not spread to distant sites (M0).
OR
T3, N0, M0: The tumor is larger than 5 cm across but does not grow into the chest wall or skin (T3). It has not spread to lymph nodes (N0) or to distant sites (M0).
- Stage III is divided into three subcategories:
- In IIIA there is breast cancer with axillary lymph nodes clumped together or attached to other structures.
- In IIIB the tumor has spread to the chestwall or skin, and may have involved lymph nodes of the axilla and/or breastbone.
- In IIIC the tumor has spread to the chest wall or skin and lymph nodes below or above the collar bone are affected.
- Stage IV is applied to metastatic breast cancer; typically lungs, liver, bone, or brain are involved.
Differences from female breast cancer
There are significant differences between male and female breast cancer. Lesions are easier to find in men due to the smaller breast size; however, lack of awareness may postpone seeking medical attention. The presence of gynecomastiaGynecomastia
Gynecomastia or Gynaecomastia, , is the abnormal development of large mammary glands in males resulting in breast enlargement. The term comes from the Greek γυνή gyné meaning "woman" and μαστός mastós meaning "breast"...
may mask the condition. The diagnosis is made later in men—at age 67 on average—than in women with their average at 63. Lesions are less contained in men as they do not have to travel far to infiltrate skin, nipple, or muscle tissue. Thus, lesions in men tend to be more advanced. Indeed, almost half of male breast cancer patients are stage III or IV. In familial cases, male BRCA2 carriers are at risk, rather than BRCA1 carriers. With the relative infrequency of male breast cancer, randomized studies are lacking.
Treatment
Treatment largely follows patterns that have been set for the management of postmenopausal breast cancer. The initial treatment is surgical and consists of a modified radical mastectomyRadical mastectomy
Radical mastectomy is a surgical procedure in which the breast, underlying chest muscle , and lymph nodes of the axilla are removed as a treatment for breast cancer....
with axillary dissection or lumpectomy
Lumpectomy
Lumpectomy is a common surgical procedure designed to remove a discrete lump, usually a benign tumor or breast cancer, from an affected man or woman's breast...
and radiation therapy with similar treatment results as in women. Also, mastectomy with sentinel lymph node
Sentinel lymph node
The sentinel lymph node is the hypothetical first lymph node or group of nodes reached by metastasizing cancer cells from a primary tumor.-Physiology:...
biopsy is a treatment option. In men with node-negative tumors, adjuvant therapy is applied under the same considerations as in women with node-negative breast cancer. Similarly, with node-positive tumors, men increase survival using the same adjuvants as affected women, namely both chemotherapy plus tamoxifen and other hormonal therapy. There are no controlled studies in men comparing adjuvant options. In the vast majority of men with breast cancer hormone receptor studies are positive, and those situations are typically treated with hormonal therapy.
Locally recurrent disease is treated with surgical excision or radiation therapy combined with chemotherapy. Distant metastases are treated with hormonal therapy, chemotherapy, or a combination of both. Bones can be affected either by metastasis or weakened from hormonal therapy; bisphosphonate
Bisphosphonate
Bisphosphonates are a class of drugs that prevent the loss of bone mass, used to treat osteoporosis and similar diseases...
s may be used to counterbalance this process and strengthen bones.
Chemotherapeutic and hormonal options in male breast cancer
Chemotherapeutic options include:- cyclophosphamideCyclophosphamideCyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....
plus methotrexateMethotrexateMethotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...
plus fluorouracilFluorouracilFluorouracil is a drug that is a pyrimidine analog which is used in the treatment of cancer. It is a suicide inhibitor and works through irreversible inhibition of thymidylate synthase. It belongs to the family of drugs called antimetabolites...
(CMF). - cyclophosphamide plus doxorubicinDoxorubicinDoxorubicin INN is a drug used in cancer chemotherapy. It is an anthracycline antibiotic, closely related to the natural product daunomycin, and like all anthracyclines, it works by intercalating DNA....
plus fluorouracil (CAF). - TrastuzumabTrastuzumabTrastuzumab is a monoclonal antibody that interferes with the HER2/neu receptor.The HER receptors are proteins that are embedded in the cell membrane and communicate molecular signals from outside the cell to inside the cell, and turn genes on and off...
(monoclonal antibody therapy).
Hormonal options include:
- Orchiectomy.
- Gonadotropin hormone releasing hormone agonist (GNRH agonist) with or without total androgen blockage (anti-androgen).
- TamoxifenTamoxifenTamoxifen is an antagonist of the estrogen receptor in breast tissue via its active metabolite, hydroxytamoxifen. In other tissues such as the endometrium, it behaves as an agonist, hence tamoxifen may be characterized as a mixed agonist/antagonist...
for estrogen receptor–positive patients. - ProgesteroneProgesteroneProgesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
. angela nelson
- Aromatase inhibitorAromatase inhibitorAromatase inhibitors are a class of drugs used in the treatment of breast cancer and ovarian cancer in postmenopausal women. AIs may also be used off-label to treat or prevent gynaecomastia in men....
s.