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

Abstract

BACKGROUND: Biological 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. METHODS: A 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. RESULTS: Fifty mutation-associated cases (19 BRCA1 cases and 31 BRCA2 cases) and 100 controls who were well matched for age (P 5.9) and tumor size (P 5.6) were included. BRCA1 and BRCA2 carriers had similar median RSs (P 5.6) and risk category stratification (P 5.3). The median RS was higher for cases versus controls (24 vs 16; P <.0001). Risk stratification also differed by mutational status (P 5.0002). 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 5.002). CONCLUSIONS: Germline 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.

Oncotype Dx recurrence score among BRCA1/2 germline mutation carriers with hormone receptors positive breast cancer

“…McAndrew et al . reported similar RS distribution among carriers and noncarriers while our series and the other two BRCA populations exhibited significantly higher RS among carriers compared with controls. We combined our data with the RS distribution found in these three studies to enlarge BRCA population for comparison.…”

“…The Oncotype Dx RS distribution of our carrier group and that of three previous studies compared with the general BC population are presented in Table . McAndrew et al .…”

“…Among them 13 BRCA1 and 14 BRCA2 mutation carriers were identified. We combined our data with 3 recent studies of RS distribution in carriers and compared the entire cohort to data in the general BC population of 82,434 women published by Genomic Health . Patients from Israeli Clalit Health Services HMO described in our population data were excluded from the combined analysis to prevent overlap with the study population based on Clalit HMO database of Lewin et al …”

BRCA mutation genetic testing implications in the United States

“…Likewise, Bayraktar et al [27] observed that overall prognosis of TN breast cancer in BRCA carriers and non-carriers was not significantly different within the first 5 years following initial diagnosis. In contrast, the aggressive nature of these breast cancers has been demonstrated through a higher median Oncotype DX recurrence score in ER-positive, node negative BRCA-associated breast cancers as compared with controls [28] and an inferior overall survival (OS) in BRCA1 mutation carriers with breast and ovarian cancer as compared with non-carrier patients. Notably, this OS difference was not seen in BRCA2 mutation carriers [29].…”

Clinical use of the Oncotype DX genomic test to guide treatment decisions for patients with invasive breast cancer

“…The spectrum of breast cancer phenotypes in BRCA2 gene mutation carriers is much more heterogeneous 55,56. Shah et al retrospectively investigated the utility of Oncotype DX in patients with BRCA1 / BRCA2 gene mutations and ER-positive breast cancer 57. Mutation carriers were more likely than age-matched controls to have RS in the intermediate- or high-risk range and overall had higher median RS.…”