Tamoxifen reduces the incidence of breast cancer in women by approximately 50% according to results from the National Surgical Adjuvant Breast and Bowel Project's Breast Cancer Prevention Trial. Women who have mutations in the breast cancer genes BRCA1 and BRCA2 are known to be at very high risk for the development of breast cancer. It is not known if tamoxifen reduces the incidence in these genetically susceptible women.

To answer this question, Dr. Mary-Claire King and colleagues identified 288 women who had developed invasive breast cancer during the Breast Cancer Prevention trial.

Mutation status for BRCA1 and BRCA2 was determined from blood samples stored from baseline examinations. Eight women with BRCA1 mutations developed breast cancer during the trial (5 on tamoxifen and 3 on placebo), and 11 women with BRCA2 mutations developed breast cancer during the trial (3 on tamoxifen and 8 on placebo).

The resulting risk ratios for developing breast cancer associated with tamoxifen use were 1.67 for women with BRCA1 gene mutations, 0.38 for women BRCA2 gene mutations, and 0.48 in women without either BRCA mutation. The risk ratios were not statistically significant because of the small number of events.

Relating the results to the biology of breast cancer, Dr. King pointed out that 80% of breast cancers that occur in women with inherited mutations in BRCA1 are negative for estrogen receptors. Tamoxifen does not reduce the incidence of estrogen receptor-negative tumors.

By contrast, 80% of breast cancers occurring in women with BRCA2 mutations are positive for estrogen receptors. The risk ratio for tamoxifen's effect in preventing estrogen receptor-positive tumors was 0.32, similar to its effect in preventing breast cancer associated with BRCA2 mutations.

Dr. King concluded that the effect of tamoxifen in reducing the incidence of breast cancer in women with BRCA2 mutations, but not in women with BRCA1 mutations, may be related to the estrogen receptor status of cancers resulting from the two breast cancer genes.

She emphasized that these results relate to prevention of breast cancer. Tamoxifen should still be used to treat all estrogen receptor-positive breast cancers, regardless of BRCA mutations.