Prognostic value of a new clinical-genomic model to predict 10-year risk of recurrence in patients with operable breast cancer.

Abstract

530 Background: Searching for a specific biomarker to predict long-term risk of recurrence for all breast cancer subtypes is challenging. DGM-CM6 (Distant Genetic Model-Clinical variable Model 6) is a new clinical-genomic prognostic model developed from the 18-gene panel which was reported previously. This study aims to validate the long-term prognostic value of this new model in all subtypes of operable breast cancer patients. Methods: We included 752 operable breast cancer patients with stage I-III in all subtypes treated in a Cancer Center from 2005 to 2014 as the internal validation (IV) cohort. The median follow-up was 94.1 months. Meanwhile, Affymetrix U133P2 (n = 1139) data obtained from GEO (GSE9195/16391/17907/19615/20711/21653/42568, EMTAB365) were collected as the external validation (EV) dataset. The prognostic effect of DGM-CM6 was then evaluated by uni- and multivariate analyses. The low- and high-risk patients ( < 33 or ≥ 33 as cut-off value) classified by DGM-CM6 were evaluated by the 10-year distant relapse-free interval (DRFI), relapse-free interval (RFI), relapse-free survival (RFS) and distant relapse-free survival (DRFS), respectively. We further compared the predictive performance between DGM-CM6/DGM and PAM50-ROR score in our IV dataset. Results: In the IV dataset, DGM-CM6 was proved to be an independent prognostic factor by multivariate analysis with hazard ratios of 3.1 (1.6-6.0) for RFS (P = 0.0009) and 3.2 (1.6-6.3) for DRFS (P = 0.0009). Significant differences were observed between low- and high-risk groups with 10-year RFI (94.0% vs. 83.5%, P < 0.0001), RFS (90.0% vs. 80.5%, P = 0.0003), DRFI (94.1% vs. 85.0%, P < 0.0001), and DRFS (90.1% vs. 81.9%, P = 0.0004), respectively. The prognostic value of RFS was convinced in the EV dataset (HR = 1.34, P = 0.00052) by the DGM only. According to C-index estimate analysis, DGM appeared to have better performance comparing with PAM50 ROR score in prediction of long-term DR, DRFS, RFI, and RFS in N0 patients (C index for distant recurrence: 0.582 by DGM, 0.528 by ROR). Conclusions: DGM-CM6 could be a new long-term prognostic model to be applied in all subtypes of operable breast cancer patients. Further validation in a large scale of clinical trials is needed.