Omission of Chemotherapy in HR+/HER2- Early Invasive Breast Cancer Based on Combined 6-IHC Score?

Abstract

Background: Previous randomized studies have assessed the possibility of omission of chemotherapy in some hormone receptor (HR)-positive and HER2-negative (HR+/HER2-) breast cancers (BC) based on gene profiling test, e.g., Oncotype DX. The goal of this study was to evaluate if combination of six proliferation related biomarkers by immunohistochemistry (6-IHC) could be a cost-effective option in determining the necessity of adjuvant chemotherapy in HR+/HER2- BC.Methods: A retrospective analysis of HR+/HER2- BC patients was conducted in the First Affiliated Hospital of China Medical University from 2010 to 2016. The expression of 6 BC-related proliferation and invasion genes (Cathepsin L2, MMP11, CyclinB1, Aurora A, Survivin and Ki67) from Oncotype DX were analyzed through IHC (designated as 6-IHC). All the included patients were divided randomly at a 7:3 ratio into training and testing cohorts. The cutoff prognosis index (PI) of 6-IHC was determined by multivariate Cox risk regression analysis after calculating the PI of each patient in training cohort and confirmed in testing cohort. The patients were classified into “Low” and “High” risk groups based on the PI value. Kaplan-Meier (KM) method was used to analyze Disease-free survival (DFS) and overall survival (OS). 6-IHC score and other factors associated with survival benefit of adjuvant chemotherapy were compared with Ki67 index.Results: A total of 330 patients were included and divided into training cohort (n = 231) and validation cohort (n = 99). The receiver operating characteristic (ROC) curve analysis showed that the patients can be divided into 6-IHC score “High” and “Low” risk groups using the cut-off PI of 2.16. The 8-year DFS and OS were 54.6% and 69.2%, respectively in the 6-IHC score “High” risk group; 85.5% and 92.5%, respectively in the 6-IHC score “Low” risk group. The 8-year DFS and OS were 70.8% and 80.9%, respectively in the Ki67 “High” risk group, 77.7% and 87.6%, respectively in the Ki67 “Low” risk group. The KM curves showed that chemotherapy did not significantly improve the DFS in the 6-IHC score “Low” risk group (p = 0.830), but significantly improved the DFS in the 6-IHC score “High” risk group (P = 0.012).Conclusions: Combined 6-IHC score could be a reliable tool in predicting cancer-specific recurrences and survival in HR+/HER2- BC patients and identifying patients who could benefit from adjuvant chemotherapy regardless of the involvement of axillary lymph node (ALN).