The effects of low HER2 expression on survival in patients with metastatic breast cancer treated with CDK 4/6 inhibitors: A multicentre retrospective study

Purpose: Endocrine therapy (ET) in combination with CDK 4/6 inhibitors (CDK 4/6i) is the standard treatment modality for hormone receptor (HR)-positive and HER2-negative metastatic breast cancer (mBC). For some authors, patients with low HER2 expression are considered a different subgroup. In this study, we aimed to investigate the prognostic effect of HER2 expression status on survival in mBC patients treated with first-line ET plus CDK 4/6i. Methods: : This multicenter retrospective study included patients with HR+/HER2-negative mBC cancer who were treated with first-line CDK 4/6i in combination with ET from January 2016 and March 2023. Patients were divided into two groups (HER2-low and zero), and survival and safety analyses were performed. Results: : A total of 201 patients were included in this study; of these, 73 (36.3%) had HER2-low disease and 128 (63.7%) had HER2-zero. There were 136 patients (67.2%) treated with ribociclib and 66 (32.8%) with palbociclib. Most of the patients (75.1%) received aromatase inhibitors as endocrine therapy. Baseline characteristics were similar between the two groups. The median follow-up was 19.1 months (range: 2.5–78.4). The most common side effect was neutropenia (22.4%). The frequency of grade 3–4 toxicity was similar between the HER2-zero and low patients (32% vs. 33.6%; p = 0.939). Visceral metastases were present in 44.8% of patients. Between the HER2-low and zero groups, median PFS (25.2 vs. 22.6 months, p = 0.972) and OS (not reached vs. 37.5 months, p = 0.707) showed no statistically significant differences. Conclusion: The prognostic value of HER2-low status remains controversial. Our study showed no significant effect of HER2 low expression on survival in patients receiving CDK 4/6i plus ET.