The discovery of genetic abnormalities associated with an increased risk of breast and other cancers is just in its infancy. The majority (two thirds) of breast cancer cases are not associated with a history of multiple family members (clusters) having the disease. The cause of the cancer in these cases is not known. Among the minority of patients with strong family histories, only a small percentage have been found to have the two specific genetic mutations identified so far, BRCA1 and BRCA2.
The BRCA1 and BRCA2 are genes (DNA) that direct the production of proteins protective against breast cancer. Mutations may occur in any of hundreds of sites on the BRCA genes. The focus of testing for BRCA mutations is on identifying specific mutations that are present in other family members of a particular patient. Such a mutation has practical clinical significance for that patient. The detection of a BRCA mutation in a patient outside the context of a family history has less relevance for several reasons. A mutation may be present but it may not alter the normal function of the gene, or it may do so to a less dangerous extent. The expression (penetrance) of a mutation varies, even in those with the family history of the same mutation. With the mutation, a particular patient may never get breast cancer or may be at the high end of the risk scale. There is also a small possibility of false negative and false positive tests. The absence of a specific mutation does not exclude other mutations. The testing is expensive and may have psychological and social consequences.
A BRCA mutation increases the lifetime risk of developing a breast cancer from about 10% to about 70% by age 70. A patient who develops a breast cancer under the age of 50 with a relative having the same history or a history of ovarian cancer at any age, has a 20% chance of carrying a BRCA mutation. Those with a mutation also have an increased risk of developing a second primary breast cancer and have an increased lifetime risk of developing ovarian cancer (20% vs. 1%). Men with the BRCA2 gene have 15 times the risk of developing breast cancer compared to the normal population. Family history in BRCA assessment must include both female and male bloodlines, not just first degree (mother, sister, daughter) female relatives.
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