Commercialization of massive parallel sequencing and reversal of patent protection for raw DNA sequences have fueled competition in the genetic testing marketplace, leading to lower costs and abundant choices for consumers. Multigene panel testing will identify a pathogenic mutation in 4 to 12% of familial high-risk patients who have tested negative for BRCA1 and BRCA2 mutation. BRCA1 and BRCA2 are still the genes most frequently implicated in hereditary breast cancer predisposition. PALB2, CHEK2, and ATM are the next most common. Variants of uncertain clinical significance are reported for 20 to 40% of tests. This is likely to improve as data accumulate. Average cancer risk can be estimated for most of the genes, but this should be adjusted up or down based on family history for management decisions. Most patients with a pathologic mutation in any of the breast cancer predisposition genes meet the criteria for enhanced surveillance with magnetic resonance imaging. Risk-reducing surgery is considered for the highest-risk patients. The results of a genetic test can influence management decisions for the newly diagnosed breast cancer patient.
This review contains 4 figures, 7 tables and 51 references
Key Words: breast cancer, chemoprevention, enhanced surveillance, hereditary predisposition, multigene panels, risk-reducing mastectomy, risk-reducing salpingo-oophorectomy
Risk-Reducing Options for Women with a Hereditary Breast Cancer Predisposition