title: Estimates of the likely prophylactic effect of tamoxifen in women with high risk BRCA1 and BRCA2 mutations.
abstract: The development of breast cancer control strategies in women at high genetic risk of breast cancer is an important issue. The likely benefit of chemopreventive approaches is of particular interest. Tamoxifen tends to be more effective in both prevention and treatment of oestrogen receptor positive tumours than oestrogen receptor negative. In this study, we combine the oestrogen-receptor specific effects of tamoxifen from randomized preventive or therapeutic trials with the oestrogen receptor status of tumours in BRCA1 and BRCA2 mutation positive women from published tumour surveys to obtain estimates of the likely effect of tamoxifen administration in mutation carriers. We used a simple two-stage procedure to estimate the benefit as a weighted average of the effect on oestrogen receptor positive tumours and oestrogen receptor negative, and using a more complex hierarchical modelling approach. Using the simple procedure and deriving the estimates of benefit from both primary prevention and therapeutic trials, we obtain an estimated reduction in risk of breast cancer from administration of tamoxifen in BRCA1 mutation positive women of 13% (RR=0.87, 95% CI 0.68--1.11). The corresponding estimated reduction in BRCA2 mutation positive women was 27% (RR=0.73, 95% CI 0.59--0.90). Using the more complex models gave essentially the same results. Using only the primary prevention trials gave smaller estimates of benefit in BRCA1 carriers but larger estimates in BRCA2, in both cases with wider confidence intervals. The benefit of prophylactic use of tamoxifen in BRCA1 mutation carriers is likely to be modest, and the effect in BRCA2 mutation carriers somewhat greater.
authors.affiliation: Department of Mathematics, Statistics and Epidemiology, Imperial Cancer Research Fund, 61 Lincoln's Inn Fields, London WC2A 3PX, UK. s.duffy@icrf.icnet.uk
authors.forename: S W
authors.initials: SW
authors.lastname: Duffy
authors.forename: R M
authors.initials: RM
authors.lastname: Nixon
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000235:genetics* / Q000517:prevention & control*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D008875:Middle Aged; D008962:Models, Theoretical; D011237:Predictive Value of Tests; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis*; D012307:Risk Factors; D013629:Tamoxifen / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004273:DNA, Neoplasm; D011960:Receptors, Estrogen; D013629:Tamoxifen