Abstract PO1-05-10: Clinical effectiveness of CDK4/6 inhibitors in HER2-low metastatic breast cancer
Authors: Frank Zhang, Jesus Anampa Mesias
Journal: Cancer Research (2024)

Abstract Introduction: There is growing evidence indicating that human epidermal growth factor 2 (HER2)-low is a unique subtype of breast cancer that comprises a substantial share of patients historically classified as HER2 negative. Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) are important in the treatment of hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer (MBC). Whether HER2-low status or the level of HER2 gene amplification have prognostic significance for HR+/HER2-negative MBC patients treated with ET and CDK4/6i remains an area of active investigation. Methods: Patients diagnosed with HR+/HER2-negative MBC and who were treated with palbociclib, ribociclib, or abemaciclib from 6/10/2015 to 12/28/2022 were selected from the Montefiore Health system database and followed until 3/24/2023. HER2-0 was defined as immunohistochemistry (IHC) 0, and HER2-low was defined as IHC 1+ or IHC 2+/in situ hybridization negative by 2018 ASCO/CAP guidelines. Median values were used to establish cutoffs for HER2/CEP17 ratio and HER2 gene copy number (GCN). Characteristics of the patients and tumors in the subgroups were compared using chi-squared/Fisher’s exact test for categorical data and Kruskal-Wallis/Wilcox signed rank tests for continuous data. Kaplan-Meier and Cox proportional hazards analysis were used to compare overall survival (OS) and progression free survival (PFS). Results: 239 patients received CDK4/6i, with 46 HER2-0 and 193 HER2-low patients. There was no statistically significant difference in clinicopathological characteristics between both cohorts. No significant differences were observed in median OS (36 vs 34 months, P &amp;gt; 0.9) and median PFS (44 vs 35 months, P = 0.4) between HER2-0 and HER2-low patients. Adjusting for HER2 status, multivariable analysis showed no statistically significant association between HER2-low status and worse OS (HR: 1.03, P = 0.9) or worse PFS (HR: 1.37, P = 0.4). The median HER2/CEP17 ratio was 1.25 (Interquartile range (IQR): 1.18-1.39), and the median HER2 GCN was 2.58 (IQR: 2.10-3.18). Median OS (25 vs 37, P = 0.15) and median PFS (35 vs 37, P = 0.15) showed no significant differences between ratio-below vs above-median patients. However, patients with GCN-below-median had significantly worse OS (25 vs 37 months, P = 0.026), with no significant difference in median PFS (38 vs 35 months, P = 0.3). Multivariate analysis revealed a significant effect of GCN-below-median on OS (HR: 0.50, P = 0.022) but not on PFS. Conclusion: The clinical effectiveness of CDK4/6i is not influenced by HER2-low status; however, the extent of HER2 gene amplification may have a substantial impact on therapy responsiveness in MBC patients undergoing CDK4/6i treatment. Table 1. Baseline characteristics of patients with MBC comparing HER2-0 vs HER2-low, above/below median HER2/CEP17 ratio, and above/below median HER2 GCN. Table 2. Median OS and PFS in patients with MBC comparing HER2-0 vs HER2-low, above/below median HER2/CEP17 ratio, and above/below median HER2 GCN. Table 3. Multivariable analysis of OS and PFS for patients with MBC comparing HER2-0 vs HER2-low, above/below median HER2/CEP17 ratio, and above/below median HER2 GCN. Citation Format: Frank Zhang, Jesus Anampa Mesias. Clinical effectiveness of CDK4/6 inhibitors in HER2-low metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-05-10.