MALE BREAST CANCER
What is male breast cancer ?
Men possess a small amount of nonfunctioning breast tissue (breast tissue that cannot produce milk) that is concentrated in the area directly behind the nipple on the chest wall. Like breast cancer in women, cancer of the male breast is the uncontrolled growth of the abnormal cells of this breast tissue.
Breast tissue in both young boys and girls consists of tubular structures known as ducts. At puberty, a girl's ovaries produce female hormones (estrogen) that cause the ducts to grow and milk glands (lobules) to develop at the ends of the ducts. The amount of fat and connective tissue in the breast also increases as girls reach puberty. On the other hand, male hormones (such as testosterone) secreted by the testes suppress the growth of breast tissue and the development of lobules. The male breast, therefore, is made up of predominantly small, undeveloped ducts and a small amount of fat and connective tissue.
How common is male breast cancer ?
Male breast cancer is a rare condition, accounting for only about 1% of all breast cancers. The American Cancer Society estimates that in 2010, about 1,970 new cases of breast cancer in men would be diagnosed and that breast cancer would cause approximately 390 deaths in men (in comparison, almost 40,000 women die of breast cancer each year). Breast cancer is 100 times more common in women than in men. Most cases of male breast cancer are detected in men between the ages of 60 and 70, although the condition can develop in men of any age. A man's lifetime risk of developing breast cancer is about 1/10 of 1%, or one in 1,000.
What are causes and risk factors of male breast cancer?
As with cancer of the female breast, the cause of cancer of the male breast has not been fully characterized, but both environmental influences and genetic (inherited) factors likely play a role in its development. The following risk factors for the development of male breast cancer have been identified.
Exposure to ionizing radiation has been associated with an increased risk of developing male breast cancer. Men who have previously undergone radiation therapy to treat malignancies in the chest area (for example, Hodgkin's lymphoma) have an increased risk for the development of breast cancer.
Hyperestrogenism (high levels of estrogen)
Men normally produce small amounts of the female hormone estrogen, but certain conditions result in abnormally high levels of estrogen in men. The term gynecomastia refers to the condition in which the male breasts become abnormally enlarged in response to elevated levels of estrogen. High levels of estrogens also can increase the risk for development of male breast cancer. The majority of breast cancers in men are estrogen receptor-positive (meaning that they grow in response to stimulation with estrogen). Two conditions in which men have abnormally high levels of estrogen that are commonly associated with breast enlargement are Klinefelter's syndrome and cirrhosis of the liver. Obesity is also associated with elevated estrogen levels and breast enlargement in men.
Klinefelter's syndrome is an inherited condition affecting about one in 1,000 men. A normal man has two sex chromosomes (X and Y). He inherited the female X chromosome from his mother and the male Y chromosome from his father. Men with Klinefelter's syndrome have inherited an extra female X chromosome, resulting in an abnormal sex chromosome makeup of XXY rather than the normal male XY. Affected Klinefelter's patients produce high levels of estrogen and develop enlarged breasts, sparse facial and body hair, small testes, and the inability to produce sperm. Some studies have shown an increase in the risk of developing breast cancer in men with this condition. Their risk for development of breast cancer is markedly increased, up to 50 times that of normal men.
Cirrhosis (scarring) of the liver can result from chronic alcohol abuse, chronic viral hepatitis, or rare genetic conditions that result in accumulation of toxic substances within the liver. The liver produces important binding proteins that affect the transport and delivery of male and female hormones via the bloodstream. With cirrhosis, liver function is compromised, and the levels of male and female hormones in the bloodstream are altered. Men with cirrhosis of the liver have higher blood levels of estrogen and have an increased risk of developing breast cancer.
Epidemiologic studies have shown that men who have several female relatives with breast cancer also have an increased risk for development of the disease. In particular, men who have inherited mutations in the breast cancer-associated BRCA-2 gene have a dramatically increased (about eightyfold) risk for developing breast cancer, with a lifetime risk of about 5%-10% for development of breast cancer. BRCA-2 is a gene on chromosome 13 that normally functions in suppression of cell growth. Mutations in this gene lead to an increased risk for development of breast, ovarian, and prostate cancers. About 15% of breast cancers in men are thought to be attributable to BRCA-2 mutation. The role of the BRCA-1 gene, which has been associated with inherited breast cancers in women, is not as clearly defined for male breast cancers.
Finasteride (Propecia, Proscar), a drug that has been used to treat benign prostatic hyperplasia and to prevent prostate cancer, may be associated with an increased risk for male breast cancer. During clinical trials for the drug, no increased risk was shown. However, over 50 cases of male breast cancer have been reported worldwide in men taking the drug. Further studies are needed to clarify whether a causal relationship between the drug and the disease actually exists.
What are the different types of male breast cancer?
The most common type of male breast cancer is infiltrating ductal carcinoma, which is also a common type of breast cancer in women. Ductal carcinoma refers to cancers with origins in the ducts (tubular structures) of the breast, and the term infiltrating means that the cancer cells have spread beyond the ducts into the surrounding tissue. On the other hand, lobular cancers (cancers of the milk glands), common in women, are extremely rare in men since male breast tissue does not normally contain lobules.
Other uncommon types of cancers of the breast that have been reported in men include ductal carcinoma in situ (cancer in the ducts that has not spread beyond the ducts themselves), cystosarcoma phylloides (a type of cancer of the connective tissue surrounding the ducts), and Paget's disease of the breast (a cancer involving the skin of the nipple). Some other types of breast cancer that occur in men are named for their growth patterns and microscopic appearance of the cancer cells, including papillary carcinoma, inflammatory carcinoma, and medullary carcinoma.
About 85% of breast cancers in men have estrogen receptors on their cell membranes. Estrogen receptors on the cell membranes allow estrogen molecules to bind to the cancer cells. Estrogen binding to the cancer cells stimulates cell growth and multiplication.
What are male breast cancer symptoms and signs?
The most common sign of breast cancer in men is a firm, nonpainful mass located just below the nipple. There may not be other associated symptoms. The average size of breast cancer in men when first discovered is about 2.5 cm in diameter. The cancer may cause skin changes in the area of the nipple. These changes can include ulceration of the skin, puckering or dimpling, redness or scaling of the nipple, or retraction (turning inward) of the nipple. Bloody or opaque discharge from the nipple may also occur. Less than 1% of cases are bilateral (occurring on both sides).
Breast cancer that has spread (metastasized) to the bones may also produce bone pain at the sites of metastases. Advanced breast cancer can also produce symptoms typical of many cancers, including malaise, weakness, and weight loss.
How is male breast cancer diagnosed?
Diagnosis of breast cancer requires identifying cancer cells in tissue specimens obtained by biopsy. Since men have little breast tissue, cancers in male breasts are easily palpable (located by feel) and, therefore, are easily accessible to biopsy. Fine needle aspiration or needle biopsy of a suspicious mass can usually establish a diagnosis. A needle is inserted into the mass and tissue from the suspicious area is withdrawn. Microscopic examination of the tissue by a pathologist establishes the diagnosis.
Other techniques that may be used to diagnose breast cancer in men include incisional (removing a portion of the suspicious tissue) or excisional (removing the mass in its entirety) biopsy of a breast mass. If nipple discharge is present, microscopic examination of a smear of the discharge can sometimes establish the diagnosis.
Imaging studies such as X-rays, CAT scans (CT scans), magnetic resonance imaging (MRI), ultrasound, and bone scans may be performed to evaluate the presence and extent of metastatic disease once the initial diagnosis of breast cancer has been made.
What is staging of male breast cancer?
Staging is carried out to determine the extent to which a cancer has spread within the body. Staging of breast cancer in men is carried out identically to the staging of breast cancer in women. The American Joint Committee on Cancer (AJCC) TNM system takes into account the tumor size, lymph node involvement by cancer, and presence of metastasis:
T: tumor size and extent of local spread
N: extent of tumor involvement of lymph nodes in the axillary (underarm) region. Since the nipple area is rich in lymphatic vessels, male breast cancer commonly spreads via the lymphatic channels to the axillary lymph nodes. (When the tumor has spread to the lymph nodes, doctors sometimes use the term "lymph node-positive" cancer.)
M: presence of distant metastases (spread to other parts of the body through the bloodstream or lymphatic vessels)
Stage 0 refers to intraductal carcinoma, in which the cancer cells have not spread beyond the boundaries of the ducts themselves.
In Stage I breast cancer, the tumor is 2 cm or less in greatest diameter and has not spread to the lymph nodes or to other sites in the body.
Stage II cancers are divided into two groups. Stage IIA cancer is either less than 2 cm in diameter with spread to the axillary lymph nodes, or the tumor is between 2 cm-5 cm but has not spread to the axillary lymph nodes. Stage IIB tumors are either larger than 5 cm without spread to the lymph nodes or are between 2 cm-5 cm in size and have spread to the axillary lymph nodes.
Stage III is considered to be locally advanced cancer. Stage IIIA means the tumor is smaller than 5 cm but has spread to the axillary lymph nodes, and the axillary lymph nodes are attached to each other or to other structures; or the tumor is greater than 5 cm in diameter with spread to the axillary lymph nodes, which may be attached to each other or to other structures. Stage IIIB tumors have spread to surrounding tissues such as skin, chest wall, and ribs, or to the lymph nodes inside the chest wall.
Stage IV cancer refers to metastatic cancer, meaning it has spread to other parts of the body. With breast cancer, metastases (sites of tumor elsewhere in the body) are most often found in the bones, lungs, liver, or brain. Stage IV cancer is also diagnosed when the tumor can be found in the lymph nodes of the neck.
What is the treatment for male breast cancer?
Like breast cancer in women, treatment depends upon the stage of the cancer and the overall physical condition of the patient. Treatments are the same as for breast cancer in women.
Most men diagnosed with breast cancer are initially treated by surgery. A modified radical mastectomy (removal of the breast, lining over the chest muscles, and portions of the axillary lymph nodes) is the most common surgical treatment of male breast cancer. Sometimes portions of the muscles of the chest wall are also removed.
After surgery, adjuvant therapies are often prescribed. These are recommended especially if the cancer has spread to the lymph nodes (node-positive cancer). Adjuvant therapies include chemotherapy, radiation therapy, targeted therapy, and hormone therapy. In cases of metastatic cancer, chemotherapy, hormone therapy, or a combination of both, are generally recommended.
Chemotherapy refers to the administration of toxic drugs that stop the growth of cancer cells. Chemotherapy may be given as pills, as an injection, or via an intravenous infusion, depending upon the types of drugs chosen. Combinations of different drugs are usually given, and treatment is administered in cycles with a recovery period following each treatment. Some of the most common chemotherapeutic agents for treating breast cancer are cyclophosphamide (Cytoxan), methotrexate (Rheumatrex, Trexall), fluorouracil, and doxorubicin (Adriamycin). In most cases, chemotherapy is administered on an outpatient basis. Chemotherapy may be associated with unpleasant side effects including hair loss, nausea and vomiting, and diarrhea.
Radiation therapy uses high-energy radiation to kill tumor cells. Radiation therapy may be delivered either externally (using a machine to send radiation toward the tumor) or internally (radioactive substances placed in needles or catheters and inserted into the body).
Hormonal therapy prevents hormones from stimulating growth of cancer cells and is useful when the cancer cells have binding sites (receptors) for hormones. Over 90% of male breast cancers express estrogen receptors and are most commonly treated with the drug tamoxifen (Nolvadex), which blocks the action of estrogen on the cancer cells. Side effects of tamoxifen treatment can include hot flashes, weight gain, mood changes, and impotence.
While estrogen is the most common target of hormonal therapy, studies have also shown that treatments directed against the actions of male hormones (anti-androgens) can also reduce the size of male breast cancer metastases. The reasons why anti-androgens are effective in widespread disease are not fully understood. Orchiectomy (removal of the testes) was formerly performed to lower androgen levels, but newer nonsurgical methods are currently favored. Drugs known as luteinizing hormone-releasing hormone (LHRH) analogs affect the pituitary gland and result in lowered production of male hormones by the testes.
Targeted therapy involves agents that are designed to specifically target one of the cancer-specific changes in cells. An example of targeted therapy is trastuzumab (Herceptin), a monoclonal antibody that blocks the activity the protein known as HER-2-neu that is made by some breast cancers. This treatment is only used in breast cancers whose cells express the HER-2-neu protein and is given intravenously. Trastuzumab has been shown to be effective in women with breast cancer but has not been extensively tested in men with breast cancer. Similarly, lapatinib (Tykerb) is a drug taken in pill form that also targets the HER2/neu protein. It is used in combination with other agents to treat HER2-positive breast cancer that is no longer responsive to trastuzumab.
If a cancer that has been surgically removed regrows at the original site, this is referred to as local recurrence. Locally recurrent cancers are usually treated by surgery along with chemotherapy or radiation therapy combined with chemotherapy.
What is the outcome (prognosis) of male breast cancer?
The prognosis of a patient with male breast cancer is considered similarly to breast cancer in a woman. As in women, the size and extent (stage) of tumor are the most important factors in the prognosis for male breast cancer. Overall survival rates for each tumor stage are similar for men and women. Since men have less breast tissue than women, it is more common for breast cancers in men to have spread beyond the breast when they are identified, resulting in a more advanced tumor stage at diagnosis.
Disease-specific five-year survival rates (meaning the percentage of patients who do not die of the disease for at least five years following diagnosis) reported for male breast cancer by stage are as follows:
Stage 0 - 100%
Stage I - 96%
Stage II - 88%
Stage III - 60%
Stage IV - 23%
These survival rates were calculated using historical data, and it is likely that current treatments will lead to even greater survival rates for those recently diagnosed.
Male Breast Cancer at a Glance
Male breast cancer is rare and accounts for only about 1% of all breast cancers.
Breast cancer risk in men is increased by elevated levels of estrogen, previous radiation exposure, and a family history of breast cancer.
Infiltrating ductal carcinoma is the most common type of male breast cancer.
A lump beneath the nipple is the most common symptom of male breast cancer.
Male breast cancer is staged (reflecting the extent of tumor spread) identically to breast cancer in women.
Surgery is the most common initial treatment for male breast cancer; chemotherapy, radiation therapy, and hormonal therapy are also administered.
The prognosis of male breast cancer, like breast cancer in women, is predominantly influenced by tumor stage.
Melissa Conrad Stöppler, MD
Dennis Lee, MD
William C. Shiel Jr., MD, FACP, FACR