Effect of BRCA1 and BRCA2 on the association between breast Cancer risk and family history

The discovery of BRCA1 and BRCA2 has led to a reassessment of the association between family history of breast/ovarian cancer and breast cancer risk after controlling for carrier status for mutations in the BRCA1 and BRCA2 genes. We examined whether family history of breast cancer remains a predictive risk factor for this disease after carrier status for BRCA1 and/or BRCA2 mutations is taken into consideration. The data are from 4730 case subjects with breast cancer and 4688 control subjects enrolled in the Cancer and Steroid Hormone Study. The probability of being a BRCA1 and/or BRCA2 gene carrier was calculated for each woman. Among predicted noncarriers, logistic regression was used to assess the relationship (odds ratios and 95% confidence intervals [CIs]) between case or control status and family history of breast or ovarian cancer. Estimates of age-specific breast cancer risk are presented by predicted carrier status. Among predicted noncarriers, case subjects were 2.06 times (95% CI = 1.69-2.50) and 1.24 times (95% CI = 1.17-1.32) more likely to report a first-degree or second-degree family history of breast cancer, respectively, than were control subjects. Case subjects were 1.99 times (95% CI = 1.63-2.44), 1.66 times (95% CI = 1.18-2.38), and 2.23 times (95% CI = 0.21-24.65) more likely to report an affected mother, sister, or both, respectively, than were control subjects. A family history of ovarian cancer was not statistically significantly associated with breast cancer risk. Noncarriers were predicted to have a lifetime risk of 9% of developing breast cancer compared with a 63% risk for carriers. Among women with a moderate family history of breast cancer, i.e., predicted noncarriers of BRCA1 and/or BRCA2 mutations, family history remains a factor in predicting breast cancer risk. In families with breast and ovarian cancers, the aggregation of these two cancers appears to be explained by BRCA1/BRCA2 mutation-carrier probability.