Tamoxifen and breast cancer incidence among women with inherited mutationsin BRCA1 and BRCA2 - National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial

Context Among cancer-free women aged 35 years or older, tamoxifen reduced t he incidence of estrogen receptor (ER)-positive but not ER-negative breast cancer. The effect of tamoxifen on breast cancer incidence among women at e xtremely high risk due to inherited BRCA1 or BRCA2 mutations is unknown. Objective To evaluate the effect of tamoxifen on incidence of breast cancer among cancer-free women with inherited BRCA1 or BRCA2 mutations. Design, Setting, and Participants Genomic analysis of BRCA1 and BRCA2 for 2 88 women who developed breast cancer after entry into the randomized, doubl e-blind Breast Cancer Prevention Trial of the National Surgical Adjuvant Br east and Bowel Project (between April 1, 1992, and September 30, 1999). Main Outcome Measure Among women with BRCA1 or BRCA2 mutations, incidence o f breast cancer among those who were receiving tamoxifen vs incidence of br east cancer among those receiving placebo. Results Of the 288 breast cancer cases, 19 (6.6%) inherited disease-predisp osing BRCA1,or BRCA2 mutations. Of 8 patients with BRCA1 mutations, 5 recei ved tamoxifen and 3 received placebo (risk ratio, 1.67; 95% confidence inte rval, 0.32-10.70). Of 11 patients with BRCA2 mutations, 3 received tamoxife n and 8 received placebo (risk ratio, 0.38; 95% confidence interval, 0.06-1 .56). From 10 studies, including this one, 83% of BRCA1 breast tumors were ER-negative, whereas 76% of BRCA2 breast tumors were ER-positive. Conclusion Tamoxifen reduced breast cancer incidence among healthy BRCA2 ca rriers by 62%, similar to the reduction in incidence of ER-positive breast cancer among all women in the Breast Cancer Prevention Trial. In contrast, tamoxifen use beginning at age 35 years or older did not reduce breast canc er incidence among healthy women with inherited BRCA1 mutations. Whether ta moxifen use at a younger age would reduce breast cancer incidence among hea lthy women with BRCA1 mutations remains unknown.