DGM-CM6: A New Model to Predict Distant Recurrence Risk in Operable Endocrine-Responsive Breast Cancer.

Lei Lei,Yunyun Zhou,Xiao-Jia Wang,Yin-Yuan Mo,Skye Hung-Chun Cheng

doi:10.3389/fonc.2020.00783

Abstract

To investigate the prognostic value of DGM-CM6 (Distant Genetic Model-Clinical variable Model 6) for endocrine-responsive breast cancer (ERBC) patients, we analyzed 752 operable breast cancer patients treated in a Taiwan cancer center from 2005 to 2014. Among them, 490 ERBC patients (identified by the PAM50 or immunohistochemistry method) were classified by DGM-CM6 into low- and high-risk groups (cutoff <33 and ≥33, respectively). Significant differences were observed between the DGM-CM6 low- and high-risk groups for 10-year distant recurrence-free survival (DRFS) in both lymph node (LN)- (P < 0.05) and LN+ patients (P < 0.05). Multivariate analysis confirmed the independent strength of DGM-CM6 for the prediction of high- vs. low- risk groups for DRFS (P < 0.0001, HR: 6.76, 95% CI, 1.8–25.42) and overall survival (P = 0.01, HR: 6.06, 95% CI:1.55–23.47), respectively. In summary, DGM-CM6 may be used to classify low- and high-risk groups for 10-year distant recurrence in both LN- and LN+ ERBC patients in the Asian population. A large scale clinical trial is warranted.

Highlights

Endocrine-responsive breast cancer patients (ERBC) generally have a better outcome than human epidermal growth factor receptor-2 (HER2)-enriched and triple negative breast cancer patients (TNBC), the risk of long-term disease recurrence is unpredictable [1]
The results presented here confirm the robustness of the distant genetic model-clinical variable model 6 (DGM-CM6) model for the prediction of long-term distant recurrence risk in both lymph node (LN) negative and LN positive endocrine-responsive breast cancer patients (ERBC) patients
Our results highlighted that within the ERBC population, not all estrogen receptor (ER)/progesterone Receptor (PR)+ HER2- samples are Luminallike since basal-like and HER2-enriched samples could be identified (Table S2). This suggests that our model can successfully predict the distance recurrence (DR) risk in ERBC patients based on the status of three IHC biomarkers what might be considerably cost-effective

Summary

Introduction

Endocrine-responsive breast cancer patients (ERBC) generally have a better outcome than human epidermal growth factor receptor-2 (HER2)-enriched and triple negative breast cancer patients (TNBC), the risk of long-term disease recurrence is unpredictable [1]. To maximize the treatment effects, adjuvant chemotherapy has been recommended for high-risk ERCB patients [2]. It is a challenge to clearly separate highand low- risk groups for distance recurrence (DR) within the ERCB population, due to the overall better outcomes compared to other subtypes. It is critically important to develop models that can accurately predict the group of patients who will benefit from endocrine therapy or chemotherapy, so that all patients can be administered appropriate treatment. Molecular biomarkers have been very helpful for predicting recurrence-free survival and overall survival in breast cancer patients. The performance of these panels has not been found to be optimal in predicting the risk of distant recurrence

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