Next-generation sequencing for hereditary breast and gynecologic cancer risk assessment

To summarize advances in next-generation sequencing and their application to breast and gynecologic cancer risk assessment. Next-generation sequencing panels of 6-112 cancer-associated genes are increasingly used in patient care. Studies report a 4-16% prevalence of mutations other than BRCA1/2 among patients who meet evidence-based practice guidelines for BRCA1/2 testing, with a high rate (15-88%) of uninterpretable variants of uncertain significance. Despite uncertainty about results interpretation and communication, there is early evidence of a benefit from multiple-gene sequencing panels for appropriately selected patients. Multiple-gene sequencing panels appear highly promising for the assessment of breast and gynecologic cancer risk, and they may usefully be administered in the context of cancer genetics expertise and/or clinical research protocols.