Effect of HER2-low expression on the efficacy of CDK4/6 inhibitors in breast cancer: A meta-analysis.

e13034 Background: The effect of human epidermal growth factor receptor 2 (HER2)-low expression on the efficacy of CDK4/6 inhibitors in breast cancer is unclear. Therefore, the aim of this meta-analysis was to determine the effect of HER2-low on the efficacy of CDK4/6 inhibitors in advanced breast cancer. Methods: We searched 10 databases and meeting minutes up to July 15, 2023, to identify studies that reported median progression-free survival (mPFS) and overall survival (OS) among HR+/HER2-low breast cancer patients and HER2-zero breast cancer patients receiving treatment with CDK4/6 inhibitors. We calculated pooled hazard ratios (HRs) and 95% confidence intervals (CIs). Results: A total of 9 retrospective studies involving 1494 patients were included. HER2-low breast cancer patients accounted for 52.48% of the sample, and HER2-zero breast cancer patients accounted for 47.52% of the sample. The mPFS was significantly worse for HR+/HER2-low breast cancer patients treated with CDK4/6 inhibitors combined with endocrine therapy than for HER2-zero breast cancer patients (risk ratio = 1.29, 95% CI: 1.15-1.44, p < 0.00001). There was no significant difference in the median overall survival (mOS) between patients with HER2-low breast cancer and patients with HER2-zero breast cancer (risk ratio = 1.07, 95% CI: 0.69-1.66%, p = 0.78). The mPFS was significantly worse for HR+/HER2-low breast cancer patients receiving first-line treatment with CDK4/6 inhibitors combined with endocrine therapy (risk ratio = 1.25, 95% CI: 1.07-1.47, p = 0.0002). Conclusions: The mPFS of patients with advanced HER2-low breast cancer and first-line salvage patients receiving CDK4/6 inhibitors combined with endocrine therapy was significantly inferior to that observed in HER2-zero breast cancer patients. However, there were no discernible differences in the mOS between the two patient groups.