Although 15 to 20 percent of men with breast cancer have a family history of MBC, only about 7 percent of the general male population has a positive family history. This disparity implies that some families carry genetic mutations that increase their risk for both male and female breast cancer.
Five to 10 percent of breast cancers that arise in women are related to genetic predisposition. Two breast/ovarian cancer genes, BRCA1 and BRCA2, which are inherited in an autosomal dominant pattern, are thought to account for 80 percent of multiple-case breast cancer families. The lifetime risk of breast cancer in affected women is 40 to 70 percent.
Inherited mutations in BRCA1 and BRCA2 also increase the risk of MBC, although not to the same absolute level of risk as in women. BRCA2 mutations are a more important predisposing factor for breast cancer in men than are BRCA1 mutations. In population-based series of men with breast cancer unselected for family history, 0 to 4 percent have BRCA1 mutations, while between 5 and 15 percent have BRCA2 mutations, depending on ethnicity and the strength of the family history. Because of this, all men diagnosed with breast cancer should be referred for genetic counseling and BRCA testing.
Men who inherit germline BRCA2 mutations have an estimated 6 percent lifetime risk of MBC; this represents a 100-fold higher risk than in the general male population. MBC in BRCA carriers is associated with young age at diagnosis and aggressive characteristics (ie, high histologic grade, HER2 overexpression).
Other genes may be involved in predisposition to MBC. Mutations in the PTEN tumor suppressor gene, which causes Cowden's syndrome, have been associated with MBC, as have mutations in mismatch repair genes (eg, hMLH1).
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Updated by Medical Writers Group, LLC, New York, for John W. Nick Foundation, Inc. - January, 2008. (Made possible through a grant provided by Cancer Research and Prevention Foundation.)
