BRCA1, BRCA2 and CHEK2 c.1100 delC mutations in patients with double primaries of the breasts and/or ovaries

Background: Previous publications and utilisation of risk models for BRCA1 and BRCA2 mutation identification suggests that multiple primary disease in an individual is a strong predictor of a BRCA1/2 mutation and that this is more predictive than the same cancers occurring in close relatives. Methods: This study assessed the pathological mutation detection rates for BRCA1, BRCA2 and the CHEK2c.1100 delC mutation in 2022 women with breast cancer, including 100 with breast/ovary double primary and 255 with bilateral breast cancer. Results and discussion: Although detection rates for mutations in BRCA1/2 are high at 49% for breast/ovarian double primary and 34% for bilateral breast cancer, the differential effect of multiple primaries in an individual appears to have been overestimated, particularly in those families with only a few malignancies. Nonetheless, bilateral breast cancer does differentially enhance detection rates in strong familial aggregations. CHEK2 1100 DelC mutation rates were lower in bilateral than for unilateral cases at 0.8% compared to 2%. The detected mutation rates for isolated double primary breast and ovarian cancer was 14% (3/22) compared to 17% (17/ 99) for the same two primaries in two close relatives in families with no other cases of breast/ovarian cancer. Risk models may need to be adjusted if further studies corroborate these findings.