A 95-gene signature stratifies recurrence risk of invasive disease in ER-positive, HER2-negative, node-negative breast cancer with intermediate 21-gene signature recurrence scores

Abstract

Purpose A subset of patients with intermediate 21-gene signature assay recurrence score may bene t from adjuvant chemoendocrine therapy, but a predictive strategy is needed to identify such patients. The 95-gene signature assay was tested to stratify patients with intermediate RS into high (95GC-H) and low (95GC-L) groups that were associated with invasive recurrence risk.Methods Patients with ER-positive, HER2-negative, node-negative breast cancer and RS 11-25 who underwent de nitive surgery and adjuvant endocrine therapy without any cytotoxic agents were included.RNA was extracted from archived formalin-xed, para n-embedded samples, and 95-gene signature was calculated.Results Two hundred six patients had RS of 11-25 (95GC-L, N = 163; 95GC-H, N = 43). In Cox proportional hazards model, 95GC-H was signi cantly associated with shorter time to recurrence than was 95GC-L (HR 5.94; 95%CI 1.81-19.53; P = 0.005). The correlation between 95-gene signature and 21-gene signature assay scores was not strong (correlation coe cient r = 0.27), which might suggest that 95-gene signature re ects biological characteristics differing from what 21-gene signature shows.Conclusions The 95-gene signature strati es patients with ER-positive, HER2-negative, node-negative invasive breast cancer and intermediate RS of 11-25 into high and low groups that are associated with recurrence risk of invasive disease. Further retrospective analysis in the prospectively-accrued TAILORx population is warranted to con rm that 95-gene signature can identify patients who would bene t from adjuvant chemoendocrine therapy.

Multicenter retrospective study on the use of Curebest™ 95GC Breast for estrogen receptor-positive and node-negative early breast cancer

“…Finally, all study participants were Japanese, and the performance when targeting other races in other countries is unknown. However, a recently published study evaluated the recurrence stratification of patients from both Japan and the US, with comparable results between populations [17].…”

Breast Cancer Patients: Who Would Benefit from Neoadjuvant Chemotherapies?

“…In addition, a 95-gene signature assay (Curebest 95GC Breast, Sysmex Corporation, Kobe, Japan), which stratifies patients into high (95GC-H) and low (95GC-L) groups, is used to predict recurrence risk in ESBC patients with ER+, HER2−, and lymph node negative (N0). Curebest 95GC assay has helped reduce the unnecessary administration of ACT [ 15 ]. A previous study has also demonstrated that the patients with ER+, HER2−, and N0 have less aggressiveness, and 85% did not experience recurrence [ 14 ].…”

“…Yao L et al reported that breast cancer patients with HER2+ or TNBC benefited from standard NACT cycles [ 21 ]. Breast cancer patients with the most common type (i.e., invasive ductal carcinoma) at low risk (RS < 10) did not benefit from receiving NACT except AET [ 15 ]. Soliman H et al generated the RS among 764 ER+, HER2− breast cancer patients with Oncotype DX test results and compared to their ability to predict pCR to NACT.…”

“…Genetic mutations, e.g., BRCA1 and BRCA2, predict the risk of hereditary breast and ovarian cancers, and different genetic signatures have also been developed for precision medicine, helping clinicians and cancer patients to choose the most appropriate therapeutic regimens. Oncotype DX (Genomic Health, Redwood, CA, USA), a gene expression profile consisting of 16 cancer-related genes (AURKA, BAG1, BCL2, BIRC5, CCNB1, CD68, CTSL2, ERBB2, ESR1, GRB7, GSTM1, MKI67, MMP11, MYBL2, PGR, SCUBE2), has been officially recommended by the National Comprehensive Cancer Network (NCCN), and widely used to calculate the recurrence score (RS) for ER+ breast cancer patients on a scale of 0-100, with ratings of low (0-10), intermediate (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25), and high risk (>26) [14]. The MammaPrint (70-gene signature, Agendia Precision Oncology, Amsterdam, The Netherlands) has been approved by the United States Food and Drug Administration (FDA) to calculate RS for both ER+ and ER-breast cancer patients.…”

“…A previous study has also demonstrated that the patients with ER+, HER2−, and N0 have less aggressiveness, and 85% did not experience recurrence [14]. The Trial Assigning Individualized Options for Treatment (TAILORx) was evaluated in a large phase III clinical trial, which compared the combination of ACT and adjuvant endocrine therapy (AET) with AET among ESBC patients with an intermediate RS (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). The results found that most cases with ESBC do not benefit from ACT.…”