Prognosis in HR-positive metastatic breast cancer with HER2-low versus HER2-zero treated with CDK4/6 inhibitor and endocrine therapy: a meta-analysis

Lin-Yu Xia; Xu-Chen Cao; Qing-Lin Hu; Wei-Yun Xu

doi:10.3389/fonc.2024.1413674

Prognosis in HR-positive metastatic breast cancer with HER2-low versus HER2-zero treated with CDK4/6 inhibitor and endocrine therapy: a meta-analysis

Front Oncol. 2024 Aug 29:14:1413674. doi: 10.3389/fonc.2024.1413674. eCollection 2024.

Authors

Lin-Yu Xia¹, Xu-Chen Cao², Qing-Lin Hu¹, Wei-Yun Xu³

Affiliations

¹ Department of Thyroid and Breast Surgery, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China.
² The First Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
³ Department of Breast Surgery, Mianyang Central Hospital, Mianyang, Sichuan, China.

Abstract

Background: The combination of CDK4/6 inhibitors (CDK4/6i) and endocrine therapy (ET) is currently the standard first-line treatment for patients with metastatic hormone receptor positive (HR+), and HER2-negative (HER2-) breast cancer. However, the impact of HER2 status on the prognosis of patients receiving CDK4/6i and ET remains unclear. The meta-analysis was conducted to evaluate different outcomes between HER2-low and HER2-zero patients in advanced HR+ breast cancer receiving CDK4/6i and ET.

Methods: A systematic search was performed in PubMed and EMBASE databases for relevant published literature. Objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) were pooled by fixed or random effects models.

Results: Overall, 12 studies with 3567 patients were eligible for analysis. The pooled analysis suggested that no significant differences were observed in terms of ORR and OS between HER2-low and HER2-zero patients who underwent CDK4/6i and ET. Similarly, no significant difference in PFS was found between HER2-low and HER2-zero patients who underwent post-line CDK4/6i and ET or first-line Palbociclib and ET. However, in patients who received mixed-line (not a single treatment line) or first-line CDK4/6i and ET, the PFS was significantly shorter in the HER2-low subgroup than in the HER2-zero subgroup (mixed-line: HR = 1.36; 95% CI = 1.11-1.65; P = 0.002; first-line: HR = 1.14; 95% CI = 1.01-1.28; P = 0.04). A similar phenomenon was observed in patients who received mixed-line or post-line Palbociclib and ET (mixed-line: HR = 1.60; 95% CI = 1.09-2.34; P = 0.02; post-line: HR = 1.43; 95% CI = 1.03-2.00; P = 0.03).

Conclusion: These results indicated that HER2-low status did not have a significant association with ORR and OS, but it may have a worse impact on PFS in patients who received mixed-line or first-line CDK4/6i and ET, as well as mixed-line or post-line palbociclib plus ET.

Keywords: CDK4/6 inhibitor; HER2-low; breast cancer; endocrine therapy; prognosis.

Grants and funding

The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.