Cross-Stratification and Differential Risk by Breast Cancer Index and Recurrence Score in Women with Hormone Receptor–Positive Lymph Node–Negative Early-Stage Breast Cancer

Abstract

Purpose: Previous results from the TransATAC study demonstrated that both the Breast Cancer Index (BCI) and the OncotypeDX Recurrence Score (RS) added significant prognostic information to clinicopathologic factors over a 10-year period. Here, we examined cross-stratification between BCI and RS to directly compare their prognostic accuracy at the individual patient level.Experimental Design: A total of 665 patients with hormone receptor-positive (HR þ ) and lymph node-negative disease were included in this retrospective analysis. BCI and RS risk groups were determined using predefined clinical cut-off points. KaplanMeier estimates of 10-year risk of distant recurrence (DR) and log-rank tests were used to examine cross-stratification between BCI and RS.Results: As previously reported, both RS and BCI were significantly prognostic in years 0 to 10. BCI provided significant additional prognostic information to the Clinical Treatment Score (CTS) plus RS (DLR-c 2 ¼ 11.09; P < 0.001), whereas no additional prognostic information was provided by RS to CTS plus BCI (DLR-c 2 ¼ 2.22; P ¼ 0.1). Restratification by BCI of the low and intermediate RS risk groups led to subgroups with significantly different DR rates (P < 0.001 and P ¼ 0.003, respectively). In contrast, restratified subgroups created by RS of BCI risk groups did not differ significantly.Conclusions: In this retrospective analysis, BCI demonstrated increased prognostic accuracy versus RS. Notably, BCI identified subsets of RS low and RS intermediate risk patients with significant and clinically relevant rates of DR. These results indicate that additional subsets of women with HR þ , lymph node-negative breast cancer identified by BCI may be suitable candidates for adjuvant chemotherapy or extended endocrine therapy.

Summary of head‐to‐head comparisons of patient risk classifications by the 21‐gene Recurrence Score® (RS) assay and other genomic assays for early breast cancer

“…RS results were compared to BCI in one study, with MMP in four studies, with ROR in four studies, and with EP/EPclin in one study . One further study, the 2016 TransATAC study, compared RS with BCI, ROR and EPclin . As to nodal status, three of 14 studies included node‐negative patients only (RS vs .…”

“…MMP by Maroun et al . 2015), while 11 of 14 studies included node‐positive patients as well . A list of the studies is shown in Table .…”

“…Risk group distribution, by each study in the current comparison. ( a ) For BCI, the intermediate group is as defined in Sestak 2016 . ( b ) The Tsai 2018 study sought to reclassify by MMP patients who were first classified as intermediate by the RS assay .…”

“…The prognostic power of Mammaprint in untreated patients was validated in the TRANSBIG study . Because of its extensive validation and wide clinical use, the RS assay is a common comparator in head‐to‐head studies with other assays …”

Multiparametric Genomic Assays for Breast Cancer: Time for the Next Generation?

“…In this issue of Clinical Cancer Research, Sestak and colleagues (1) compare the performance of a 7 gene prognostic score (Breast Cancer Index, BCI, Biotheranostics, San Diego, CA), with a 21 gene prognostic score (Oncotype Dx, RS, Genomic Health, Redwood City, CA) in a retrospective cohort of 665 patients with hormone receptor positive, lymph node negative early stage breast cancer treated with tamoxifen or anastrozole alone (no chemotherapy) in the Anastrozole, Tamoxifen, Alone or in Combination (ATAC) trial. In particular, these authors compare the prognostic accuracy of both in cases where these assays yielded discordant results.…”