Tamoxifen and breast cancer risk in women harboring a BRCA1 germline mutation: computed efficacy, effectiveness and impact.

The management of breast cancer prone women remains a tough issue despite the release of institutional guidelines. Currently, only the anti-estrogen agent Tamoxifen and prophylactic surgery are claimed to decrease breast cancer incidence. However, efficacy of Tamoxifen, particularly in BRCA1 gene carriers, remains controversial and acceptability of prophylactic surgery is low. To evaluate the expected impact of Tamoxifen in preventing hereditary breast cancers, a modelling was made according to the efficacy of the treatment with respect to biological predictors of response: estrogen receptor (ER) and pS2 status of a series of 33 BRCA1-related breast cancers (BRCA1-BCs), and using data on BRCA1-BCs penetrance, as well as compliance and acceptability of the strategy. Although, 88% of BRCA1-BCs are ER negative in our series, 30% of cases are pS2 positive, implying a potential hormonal sensitivity of a proportion of these cancers. From our modelling, the expected impact of Tamoxifen in BRCA1 gene carriers is a reduction of breast cancer incidence of about 10% according to acceptability and compliance, close to that of 5% and of 13.5% for prophylactic mastectomy, according to acceptability rates from US and French surveys respectively. Since autonomy of choice is the root of western ethics, cancer prone women should be informed about the low but valuable expected reduction of incidence of breast cancer using Tamoxifen preventive therapy.