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Narod et al, using data collected from the international Hereditary Breast Cancer Clinical Study Group, have compared tamoxifen use between 209 mutation carriers with bilateral breast cancer (that is, cancer in both breasts) and 384 mutation carriers with unilateral disease [Narod, S.A. et al (2000) Lancet 356, 1876-1881]. In a matched case-control study they found that women with bilateral disease were less likely to have been treated with tamoxifen for the first cancer than were women with unilateral disease. The multivariate odds ratio for contralateral breast cancer with tamoxifen use was 0.5 (95% confidence interval 0.28-0.89). Oophorectomy and chemotherapy also protected against contralateral breast cancer and their effects appeared to be independent of that of tamoxifen. The protective effects of tamoxifen and chemotherapy only seemed to last for up to about 10 years, whereas oophorectomy gave lasting protection against contralateral disease.

Comment: It has been difficult, in the years since the discovery of the BRCA1 and BRCA2 genes, to know what treatment and/or prophylaxis to recommend for women carrying mutations in these genes as it has not been clear whether their cancers respond in the same way as the 95% of breast cancer cases not associated with these genes. Information is, however, now beginning to accumulate and the study of Narod et al is a useful addition to the evidence base. It is interesting, but not yet explicable, that the protective effect of tamoxifen in their study was significantly greater in North American centres than in Europe. A similar effect has been seen in large prevention trials with tamoxifen.