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 80-fold) 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.
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