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 health 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 means that the male breasts are 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 have proteins on the surface of the cells that can receive and transport estrogen through the cell wall and into the interior of the cell). Two medical 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. Certain medications can cause gynecomastia as a side effect when taken for long periods. These include several types of medicine used to treat high blood pressure, medicines to reduce stomach acid, valium, finasteride, medicines to treat prostate cancer, and others. Check the side effects of the medicines you take if you think you may be developing male breast tissue enlargement (gynecomastia).
Klinefelter's syndrome is an inherited health 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
Cirrhosis 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 free and protein-bound 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 an increased risk for developing breast cancer, with a lifetime risk of about 6 in 100 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. A portion of breast cancers in men are thought to be attributable to BRCA-2 mutation. Mutations in the BRCA-1 gene, which has been associated with inherited breast cancers in women, increase the risk for male breast cancer to a lesser degree than mutations in BRCA-2 (lifetime risk of 1 in 100).
Other genetic mutations have also been associated with an increase in risk for breast cancer in men, including mutations in the PTEN tumor suppressor gene (Cowden’s syndrome), TP53 mutations (Li-Fraumeni syndrome), PALB2 mutations, and mutations associated with hereditary nonpolyposis colorectal cancer (Lynch syndrome).
Finasteride (Propecia, Proscar), a drug that has been used to treat baldness, as well as benign prostatic hyperplasia (prostate enlargement) 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.