s2 We are currently focusing on the interplay of genes and environment in the development of estrogen receptor (ER)-negative breast cancer, which is aggressive, less responsive to treatment, and more likely to strike young women and those of African ancestry. Unfortunately, there are no strategies to prevent ER-negative breast cancer and research is urgently needed. Nevertheless, we have made progress in understanding genetic risk factors for some familial forms of breast cancer, which is reason enough to adopt family-based interventions for breast cancer prevention, especially among families with identifiable highly penetrant mutations in breast cancer susceptibility genes. In 1997, I chaired the ASCO Task Force on Cancer Genetics Education, charged to educate oncologists about the importance of genetics in clinical oncology practice. Since then, a growing body of evidence documents the benefits of preventive measures with minimal risk to women with identifiable highly penetrant mutations in BRCA1 and BRCA2 genes. Whereas other genes, such as TP53 in Li-Fraumeni Syndrome and PTEN in Cowden syndrome, contribute to a small fraction of hereditary breast cancer, mutations in these genes are rare. Germ-line mutations in BRCA1 or BRCA2 are strong predictors of breast and/or ovarian cancer development, and the contribution of these mutations to breast cancer risk within any specific population is a function of both their prevalence and penetrance. Mutation prevalence varies among ethnic groups and may be influenced by founder mutations as observed in Ashkenazi Jews and Icelanders. Although estimates of mutation prevalence and penetrance rates are inconsistent and occasionally controversial, understanding them is critical for providing individualized risk assessment. Although the contribution of other genes to early onset and familial breast cancer needs clarification, genetic testing for BRCA1 and BRCA2 has become standard of care and an important component of personalized breast cancer risk assessment and prevention.
Variants in estrogen-biosynthesis genes CYP17 and CYP19 and breast cancer risk: a family-based genetic association study
