ASCO GUIDELINES Bundle

8 Management Table 1. Management of Hereditary Breast Cancer in BRCA1/2 vs. Moderate Penetrance Genes Risk-Reduction/Second cancer e following factors should be considered for assessing risk of contralateral breast cancer (CBC) and role of risk-reducing mastectomy in BRCA1/2 mutation carriers: age of diagnosis (the strongest predictor of future contralateral breast cancer; family history of breast cancer, overall prognosis from this or other cancers (e.g., ovarian), ability of patient to undergo appropriate breast surveillance (MRI), comorbidities, and life expectancy. For women with breast cancer who have a BRCA1/2 mutation and who have been treated or are being treated with unilateral mastectomy, contralateral risk-reducing mastectomy (CRRM) should be offered. CRRM is associated with a decreased risk of contralateral breast cancer; there is insufficient evidence for improved survival. e following factors should be considered for assessing risk of CBC and role of risk- reducing mastectomy: age of diagnosis (the strongest predictor of future contralateral breast cancer), family history of breast cancer, overall prognosis from this or other cancers (e.g., ovarian), ability of patient to undergo appropriate breast surveillance (MRI), comorbidities, and life expectancy. For breast cancer patients with a deleterious germline BRCA1/2 mutation interested in risk-reducing mastectomy, physicians should discuss the option of nipple-sparing mastectomy as a reasonable oncologic option. BRCA1/2 mutation carriers who do not have bilateral mastectomy should undergo high- risk breast screening of remaining breast tissue with annual mammogram and MRI. Systemic Therapy Recommendations When offering chemotherapy for germline BRCA mutation carriers with metastatic breast cancer, platinum chemotherapy is preferred to taxane therapy for patients who have not previously received platinum. ere are no data to address platinum efficacy in other germline mutation carriers. For germline BRCA mutation carriers with breast cancer treated with (neo)adjuvant therapy, data do not support the routine addition of platinum to anthracycline and taxane-based chemotherapy. While single-agent platinum has demonstrated activity in the neoadjuvant setting, there are no data yet comparing it to standard chemotherapy. ere are no data to address platinum efficacy in other germline mutation carriers. For BRCA1/2 mutation carriers with metastatic HER2-negative breast cancer, olaparib or talazoparib should be offered as an alternative to chemotherapy in the 1st-3rd line setting. For BRCA1/2 mutation carriers with metastatic HER2-negative breast cancer, there are no data directly comparing efficacy of PARP inhibitor to platinum chemotherapy. (cont'd)

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