Abstract

Abstract Introduction: Outcomes have greatly improved for patients with HER2+ breast cancer. Recently, tumors with IHC 1+ or 2+/negative FISH have been classified as ‘HER2-low’. The development of novel HER2 agents has shown clinical benefit in this subset of patients. Information on the clinical characteristics of these patients which could be prognostic, and which could impact therapeutic options is limited. Methods: This was an IRB-approved study. Relevant patient demographics, disease characteristics, and treatment details of patients with metastatic breast cancer seen at our center from 2018 to 2021 were collected by chart review. All data analyses were performed using R version 4.3.1, and a p-value ≤ 0.05 was considered statistically significant. Results: A total of 102 patients with metastatic breast cancer were included. Patients were divided as HER2+, HER-, HER2 low ER+ and HER2 low ER -. 66.6% of patients had HER2 low disease. Patients with HER2 low ER- disease were more likely to have tumors that were of higher grade (grade 3, 71.4%, p=0.003), higher mean Ki67 (60%, p<0.001), and of ductal histology (100%, p=0.006). There was a statistically significant difference in PFS among the four groups (p=0.001). Median survival was longer in patients with HER2 low ER+ compared to the HER2- group. (1.42 vs 0.58, p<0.001, Table 1). Amongst HER2 low ER+ patients, there was a significant PFS difference in those treated with CDK4/6 inhibitors compared to chemotherapy (2.83 vs. 0.67, p=0.009). We found no difference in PFS between patients who were HER2 1+ ER+ and HER2 2+ ER+. In multivariate analysis, there was no significant association of race, grade, menopausal status, Ki67, histologic subtype, and metastatic sites with PFS. Table 1. PFS Summary Group Total number Progression/Death Median Survival HER2- 13 13 0.58 HER2 low ER- 14 11 0.88 HER2 low ER+ 54 32 2.42 HER2+ 20 12 1.08 Conclusion: In this small single-center retrospective study, patients with metastatic HER2 low ER- breast cancer had higher-grade tumors. HER2 low ER+ patients had a better PFS compared to HER2- patients. This seems to suggest that the HER2 low group may have some inherent biologic differences. Larger studies are needed. Citation Format: Radhika Kulkarni, Muhammad Ali Shahid, Oscar Hinojosa Castro, Kunj Patel, Chun-Hui Lin, Courtney Rose, Vrushali Dabak. Understanding the new subgroup- Her 2 low breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2563.

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