Impact of HER2‐low expression on the efficacy of endocrine therapy with or without CDK4/6 inhibitor in HR‐positive/HER2‐negative metastatic breast cancer: A prospective study

Abstract Background CDK4/6 inhibitors in combination with traditional endocrine therapy (ET) have become the recommended first‐line therapy for HR‐positive/HER2‐negative metastatic breast cancer (MBC). The aim of this prospective study was to evaluate the relationship between HER2‐low expression and clinical outcomes in HR‐positive/HER2‐negative MBC patients receiving ET with or without CDK4/6 inhibitors. Methods Between April 2016 and November 2019, 233 women with HR‐positive/HER2‐negative MBC who received ET with or without CDK4/6 inhibitors were enrolled into the study. The primary endpoint was progression‐free survival (PFS). Statistical analysis included descriptive statistics, Kaplan–Meier curves, and Cox proportional hazards models. Results HER2‐low and HER2‐zero subgroups in the CDK4/6 inhibitor plus ET cohort showed no significant difference in the median PFS (10.9 vs. 8.0 months; hazard ratio: 0.92; 95% confidence interval CI: 0.64–1. 30; p = 0.65), while HER2‐low subgroup showed a significantly shorter median PFS compared to the HER2‐zero subgroup in the ET alone cohort (5.6 vs. 17.0 months; hazard ratio: 2.82; 95% CI: 1.34–5.93; p = 0.0044). Moreover, the objective response rate was significantly lower in the HER2‐low subgroup than the HER2‐zero subgroup in the ET alone cohort (10.5% vs. 40.0%, p = 0.047). Lastly, no significant difference was observed in the overall survival between the HER2‐low and HER2‐zero subgroups in both cohorts. Conclusion This study suggested that HER2‐low expression may predict the efficacy of ET but not that of CDK4/6 inhibitor plus ET in HR‐positive/HER2‐negative MBC patients. The results of this study highlight the importance of integrating HER2 status in tailoring personalized treatment strategies for HR‐positive MBC.