Comparison of StemPrintER with Oncotype DX Recurrence Score for predicting risk of breast cancer distant recurrence after endocrine therapy

Abstract

Objective: Molecular tests predicting the risk of distant recurrence (DR) can be used to assist therapy decision-making in oestrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer patients after considerations of standard clinical markers. The Oncotype DX Recurrence Score (RS) is a widespread tool used for this purpose. Here, we compared the RS with the StemPrintER Risk Score (SPRS), a novel genomic predictor with a unique biological basis in its ability to measure the expression of cancer stemness genes.

Materials and methods: We benchmarked the SPRS vs. RS, alone or in combination with clinicopathological variables expressed by the Clinical Treatment Score (CTS), for the prognostication of DR in a retrospective cohort of 776 postmenopausal patients with ER+/HER2-breast cancer enrolled in the translational arm of the randomised Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial. Likelihood ratio (LR) with χ² test and C-index were used to assess prognostic performance for the entire ten-year follow-up period and in early (0-5 years) and late (5-10 years) intervals.

Results: In all patients, the SPRS provided significantly more prognostic information than the RS for ten-year DR prognostication (C-index = 0.688, LR-χ² = 33.4 vs. C-index = 0.641, LR-χ² = 22.1) and for late (5-10 years) DR prognostication (C-index = 0.689, LR-χ² = 18.8 vs. C-index = 0.571, LR-χ² = 4.7). The SPRS also provided more prognostic information than the RS when added to the CTS in all patients (CTS + SPRS: LR-Δχ² = 14.9; CTS + RS: LR-Δχ² = 9.7) and in node-negative patients (CTS + SPRS: LR-Δχ² = 11.7; CTS + RS: LR-Δχ² = 6.6).

Conclusions: In postmenopausal ER+/HER2- breast cancer patients, SPRS provided more prognostic information than RS for DR when used alone or in combination with the CTS. The SPRS could therefore potentially identify high-risk patients, who might benefit from aggressive treatments, from low-risk patients who might safely avoid adjuvant chemotherapy or prolongation of endocrine therapy.

Keywords: Biomarkers; Breast cancer; Cancer stem cells; Metastasis; Prognostic genomic tools.