Public health aspects of breast cancer gene testing in Canada. Part 1: risks and interventions

The risks (penetrance) of breast and ovarian cancer in carriers of the BRCA1 or BRCA2 genes are high, but it is likely that estimates based on selected large multicase families are inflated by selection bias. Estimates based on a population survey of Ashkenazi Jews are lower, but other population-based estimates are still not available. The proportion of breast or ovarian cancers related to the genes is similarly lower in population-based samples than in referred selected families, and, even for subjects with cancer onset at young ages or with a family history, it is quite small. Other genes with lower prevalence are also important, and there is evidence of some gene environmental interactions. The management of female BRCA gene carriers includes intensive surveillance, prophylactic surgery and the use of tamoxifen. Apart from screening justified by randomized trials in the general community, such as mammography, recommendations for surveillance and prophylactic surgery are based only on expert opinion, and there has been little consideration of risk-benefit or cost-benefit comparisons. Tamoxifen reduced breast cancer incidence in one trial of high-risk women, but not in two other smaller trials, and the effect on mortality has not been determined. The limitations of genetic testing, and particularly of intervention strategies, deserve close scrutiny.