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

Background: The discovery of BRCA1 and BRCA2 has led to a reassessment of t he association between family history of breast/ovarian cancer and breast c ancer risk after controlling for carrier status for mutations in the BRCA1 and BRCA2 genes. We examined whether family history of breast cancer remain s a predictive risk factor for this disease after carrier status for BRCA1 and/or BRCA2 mutations is taken into consideration, Methods: The data are f rom 4730 case subjects with breast cancer and 4688 control subjects enrolle d 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 n oncarriers, logistic regression was used to assess the relationship (odds r atios and 95% confidence intervals [CIs]) between case or control status an d family history of breast or ovarian cancer. Estimates of age-specific bre ast cancer risk are presented by predicted carrier status. Results: Among p redicted noncarriers, case subjects were 2.06 times (95% CI = 1.69-2.50) an d 1.24 times (95% CI = 1.17-1.32) more likely to report a first-degree or s econd-degree family history of breast cancer, respectively, than were contr ol 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 signifi cantly associated with breast cancer risk. Noncarriers were predicted to ha ve a lifetime risk of 9% of developing breast cancer compared with a 63% ri sk for carriers. Conclusions: 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 fami lies with breast and ovarian cancers, the aggregation of these two cancers appears to be explained by BRCA1/BRCA2 mutation-carrier probability.