Abstract

Abstract Context: Breast cancers with a HER2 immunohistochemistry (IHC) result of 1+ or 2+ and a negative amplification test (FISH), previously treated as HER2 negative, are now termed HER2-low and are being targeted for treatment. We aim to explore the clinical significance of this group. Design: 394 breast cancer cases were included from our institution from 2010. Demographic and clinicopathological data on receptors status, recurrence/metastasis, treatment, and survival was collected. HER2 was re-evaluated according to the 2018 CAP ASCO guidelines and patients were treated according to standardized protocol. HER2 +2 with positive FISH and HER2 +3 were excluded. HER2-low was compared to HER2-0. Appropriate statistical analysis was performed. Results: 394 patients (76% IDC; 8% ILC; 16% others) were included, such that 91 (23%) were HER2-0 and 303 (77%) HER2-low. Median age was 58 years (range: 25-95). Median follow-up was 54 months (range: 0.5-259). Grade 3 tumors were significantly more frequent in HER2-0 than HER-2 low (52% vs. 33%; p=0.010). Grade 3 or ILC patients had higher risk of recurrence than Grade 1 (HR 2.55; p< 0.001) or IDC (HR 2.03; p=0.033). After adjusting for grade, HER2-low had a significantly worse RFS than HER2-0 (HR 1.58; p=0.043). In the ER negative subgroup, HER2-low had significantly worse RFS than HER2-0 (HR 2.02; p=0.023). No differences in overall survival were seen. Conclusions: Our data showed higher recurrence in HER2-low group compared to HER2-0. This suggests that breast cancer patients with HER2- low are a separate entity and might benefit from additional targeted therapy. Table 1 Hazard regression analysis of risk factors associated with recurrence Citation Format: Fadi Zaiem, Asem AbuJamea, Mira Kheil, Anna Numi, Omar Abbas, Sanaa Awada, Ragad Almsaddi, Saleh Al-Juburi, Lauren Larson, Deepti Jain, Maya AlSaghir, Hyejeong Jang, Seongho Kim, Sudeshna Bandyopadhyay, Sunil Jaiman, Rouba Ali-Fehmi. Clinical Significance of HER2-low 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 PO3-01-11.

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