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Abstract
Approximately 10% of breast cancer cases are attributed to a hereditary predisposition. Here, we review the risks and management options for highly penetrant genes including BRCA1/2, TP53, PTEN, CDH1, STK11, and PALB2 which confer a 5 to greater than 10-fold increased risk of breast cancer, and an increased risk of other cancers. Risk-reducing salpingo-oophorectomy (RRSO) reduces mortality in BRCA1/2 carriers. Other management strategies are tailored to the hereditary cancer syndrome in question and include more intensive screening with imaging and serologic studies, risk-reducing surgeries such as mastectomy, and consideration of risk reduction agents. Given the advances in our knowledge regarding the impact of management strategies in mutation carriers, genetic testing for high-penetrance breast cancer genes has become standard of care. It is critically important to discuss the implications of testing unaffected family members, in order to be able to offer impactful interventions to healthy at-risk individuals.
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