Management of Hereditary Breast Cancer: American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Guideline

Patients with newly diagnosed BC and <i>BRCA1</i>/<i>2</i> mutations may be considered for breast-conserving therapy (BCT), with local control of the index cancer similar to that of noncarriers. The significant risk of a contralateral BC (CBC), especially in young women, and the higher risk of new cancers in the ipsilateral breast warrant discussion of bilateral mastectomy. Patients with mutations in moderate-risk genes should be offered BCT. For women with mutations in <i>BRCA1</i>/<i>2</i> or moderate-penetrance genes who are eligible for mastectomy, nipple-sparing mastectomy is a reasonable approach. There is no evidence of increased toxicity or CBC events from radiation exposure in <i>BRCA1</i>/<i>2</i> carriers. Radiation therapy should not be withheld in <i>ATM</i> carriers. For patients with germline <i>TP53</i> mutations, mastectomy is advised; radiation therapy is contraindicated except in those with significant risk of locoregional recurrence. Platinum agents are recommended versus taxanes to treat advanced BC in <i>BRCA</i> carriers. In the adjuvant/neoadjuvant setting, data do not support the routine addition of platinum to anthracycline- and taxane-based chemotherapy. Poly (ADP-ribose) polymerase (PARP) inhibitors (olaparib and talazoparib) are preferable to nonplatinum single-agent chemotherapy for treatment of advanced BC in <i>BRCA1</i>/<i>2</i> carriers. Data are insufficient to recommend PARP inhibitor use in the early setting or in moderate-penetrance carriers. Additional information available at www.asco.org/breast-cancer-guidelines.