9
Table 1. Management of Hereditary Breast Cancer in
BRCA1/2 vs. Moderate Penetrance Genes
Systemic Therapy Recommendations (cont'd)
For patients with early-stage, HER2–negative breast cancer with high risk of recurrence
and germline BRCA1 or BRCA2 pathogenic or likely pathogenic variants, one year of
adjuvant olaparib should be offered aer completion of (neo)adjuvant chemotherapy
and local treatment, including radiation. For those who had surgery first, one year
of adjuvant olaparib should be offered for patients with triple negative breast cancer
(TNBC) and tumor size >2 cm or any involved axillary nodes. For those with hormone
receptor-positive disease, one year of adjuvant olaparib should be offered to those
with at least four involved axillary lymph nodes. For patients who had neoadjuvant
chemotherapy, one year of adjuvant olaparib should be offered to patients with TNBC
and any residual cancer; for patients with hormone receptor-positive disease, one year of
adjuvant olaparib should be offered to patients with residual disease and a clinical stage,
pathologic stage, estrogen receptor status, and tumor grade (CSP+EG) score ≥3.
Women with Breast Cancer Who Have a Mutation in a Moderate-Penetrance
Gene
Local Therapy Recommendations
Index/Current Cancer
For women with newly diagnosed breast cancer who have a mutation in a moderate-
penetrance breast cancer susceptibility gene, mutation status alone should not
determine local therapy decisions for the index tumor or contralateral risk-reducing
mastectomy.
In breast cancer patients with a mutation in a moderate-penetrance breast cancer
susceptibility gene, BCT should be offered to patients for whom BCT is an appropriate
treatment option. ere is a lack of data regarding ipsilateral breast cancer events aer
BCT among patients with moderate-risk mutations.
For women with newly diagnosed breast cancer undergoing mastectomy who have a
deleterious mutation in moderate-penetrance genes, nipple-sparing mastectomy is a
reasonable oncologic approach to consider in appropriately selected patients.
For women with breast cancer who are carriers of an ATM mutation, radiation therapy
should be offered when clinically indicated. Data regarding rates of toxicity between
ATM mutation carriers and non-carriers are limited and inconsistent. Potential absolute
risks appear to be small; however, more research is needed. Discussion with ATM
carriers interested in BCT is encouraged.
(cont'd)
