Twenty-one-gene recurrence score assay in BRCA-associated versus sporadic breast cancers: Differences based on germline mutation status

BACKGROUNDBiological differences between BRCA-associated breast cancer and sporadic breast cancer may warrant different adjuvant chemotherapy (ACRx) recommendations despite similar phenotypic features. A 21-gene expression profile (Oncotype DX) generates a prognostic recurrence score (RS) that predicts the ACRx benefit in patients with hormone receptor-positive breast cancer. No reports describe assay results for BRCA-associated breast cancer. METHODSA review of Memorial Sloan Kettering Cancer Center databases identified 4908 patients with hormone receptor-positive, node-negative breast cancer who underwent Oncotype DX testing between July 2006 and March 2014. BRCA1/BRCA2 carriers (cases) were identified and matched (1:2) by age at diagnosis and tumor size to noncarrier controls. Two-sample nonparametric tests were used to compare the baseline characteristics, RSs, and risk stratification between BRCA1 and BRCA2 patients. Conditional logistic regression was used to assess these differences by mutational status. RESULTSFifty mutation-associated cases (19 BRCA1 cases and 31 BRCA2 cases) and 100 controls who were well matched for age (P=.9) and tumor size (P=.6) were included. BRCA1 and BRCA2 carriers had similar median RSs (P=.6) and risk category stratification (P=.3). The median RS was higher for cases versus controls (24 vs 16; P<.0001). Risk stratification also differed by mutational status (P=.0002). Cases had more high-risk disease (28% vs 7%) and intermediate-risk disease (56% vs 36%) and less low-risk disease (16% vs 57%). Cases were more likely than controls to receive ACRx (74% vs 46%; P=.002). CONCLUSIONSGermline BRCA-associated hormone receptor-positive breast cancer may be associated with intrinsically less favorable biology. Few affected carriers have RS indicating a clear absence of benefit from ACRx. The increased use of ACRx and benefit from ACRx in BRCA carriers may mitigate otherwise inferior outcomes. Cancer 2016;122:1178-84. (c) 2016 American Cancer Society. BRCA-associated tumors have Oncotype DX recurrence scores that are significantly different than those of sporadic tumors, with few carriers having a recurrence score indicative of a clear absence of benefit from adjuvant chemotherapy. These findings yield insight into the biology of these tumors, have implications for the benefit of adjuvant chemotherapy in patients with germline alterations, and call for validation of the recurrence score assay in BRCA-associated breast cancers.