Prognostic Predictors Do Not Equate to Predictors of Chemotherapy Benefit in HR-Positive, HER2-Negative Breast Cancer: A Population-Based Study

Abstract Background: Patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), early breast cancer had a favorable prognosis. We conducted a study to identify patients benefiting from adjuvant chemotherapy in this cohort.Methods: Patients with HR+, HER2-, early breast cancer were identified from the SEER database and were classified into the chemotherapy and non-chemotherapy groups. A propensity score matching (PSM) was performed and subgroup analyses were conducted in the after-matched patients to explore which subgroups benefited from chemotherapy. Gene expression RNA-seq data and phenotypic data of HR+, HER2-, early breast cancer were identified from the TCGA database, differentially expressed genes (DEGs) from paired tumor and normal samples were identified, and DGEs were filtered through interactions between chemotherapy and gene expression level to obtain genes associated with chemotherapy benefits. A chemotherapy predictive clinical score (CPCS) and a chemotherapy predictive genetic score (CPGS) were established respectively based on variables or genes identified.Results: In total, 86158 patients with HR+, HER2-, early breast cancer were identified from the SEER database and there were 15259 patients in each after-matched group. Race, T stage and N stage were associated with chemotherapy benefits and entered into the establishment of CPCS. Amongst the 29 normal samples and 254 tumor samples of HR+, HER2-, early breast cancer in the TCGA database, 29 pairs of samples were identified to filter 1709 DEGs, of which 84 DGEs were associated with chemotherapy benefits. SOWAHA、RP11-205M3.3、IRX6、PPBP and EMX1 were chosen to establish the CPGS according to their P-values for interaction.Conclusions: Nodal status was an important indicator for chemotherapy decisions in HR+, HER2-, early breast cancer and most patients without nodes involved could be spared chemotherapy. In addition, a CPCS and a CPGS were established respectively using a completely new method to identify patients benefiting from chemotherapy.