BRCA mutations occur in approximately 20% of families with inherited susceptibility to breast cancer. Personal and family characteristics associated with an increased likelihood that a BRCA mutation will be identified are listed in Table 3. Breast cancers in BRCA1 carriers often have medullary features, are more likely to be poorly differentiated with high mitotic rates and S-phase fraction, lack an in situ component, have low estrogen and progesterone receptors score, and node-positive. BRCA2 tumors are more histologically heterogeneous and more likely to be estrogen-receptor-positive. For BRCA1 carriers, breast cancer survival rates are similar to those for sporadic cancer patients when controlling for stage. The lifetime risk for second primary breast cancers in BRCA-mutation carriers with breast cancer is 40-60%, with 5-year risk estimates of 22-31%. The lifetime risk for male breast cancer in BRCA2-mu-tation carriers has been reported to be approximately 6.3%. The average age of onset of ovarian cancer is 48-54 years in BRCA1 carriers and 62 years in BRCA2 carriers, similar to onset ages in sporadic cases. Ninety-four percent of BRCA1 ovarian tumors have serous histology (60% in sporadic cases).
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