Abstract

e12578 Background: Breast cancer is the most diagnosed cancer in women. The 5-year overall survival (OS) rate in early-stage disease is 97% while in advanced disease is 36%. HER2 is a growth receptor involved in cell survival and proliferation. An overexpression of this protein leads to a more aggressive behavior; however, with targeted therapies, OS has improved. Recently, a new classification has been developed for tumors previously known as HER2-negative: HER2-low; which are those with IHC 1+ or 2+/ISH negative. It is believed that in these types of tumors, the signaling pathways of the HER2-positive subtype are also activated. There are conflicting studies on the prognostic impact of this subgroup. Currently, there is availability of anti-HER2 treatment for patients in advanced stages, as described in the DESTINY-Breast04 study, which changes the treatment paradigm for this pathology. Methods: The aim of this study is to determine overall survival in patients with HER2-low breast cancer. A retrospective, analytical, observational cohort was performed. Patients diagnosed with HER2-negative/low breast cancer, treated at the UMAE Oncology Hospital of the CMN Siglo XXI, from January 2018 to December 2022, were included. OS and disease-free survival (DFS) were calculated using Kaplan-Meier curves, and the impact of HER2-low expression on OS and DFS was assessed using log-rank analysis. The prognostic analysis of the complete model was performed using a Cox proportional hazards model. Results: We included 213 patients. The median age was 57 years. Ninety-five patients were HER2-low (44.6%), and 118 were HER2-negative (55.4%). Seventy-six percent had positive hormone receptor (HR) status. Patients with HR+/HER2-negative were 84 (52.2%), and HR+/HER2-low were 77 (47.8%). Among HR-negative status, the majority were HER2-negative (65.4%). When comparing HER2-negative and HER2-low, no statistically significant differences were found, with a 48-month overall survival of 70% for HER2-negative compared to 87.1% for HER2-low (p= 0.5700). OS analysis in the HER2-low group, comparing HR+ vs. HR-, a statistically significant difference at 48 months of 98.31% vs. 49.17% (p <0.0001), respectively, was found. Regarding DFS, a comparison between HR+ against HR-, it was 79.53% vs. 37.14%, respectively (p= 0.0002). The DFS analysis revealed that, among the variables studied, lymphovascular invasion (LVI) and HR+ status showed a statistically significant association with time to recurrence. Particularly, the presence of HR positivity was associated with a significant 82.6% reduction in the risk of recurrence. Conclusions: HER2 status alone (negative or low) did not offer a clear distinction in terms of OS or DFS. Nevertheless, it was observed a difference in OS and DFS outcomes favoring the HR-positive group when examining HR status among individuals with HER2-low, though this finding requires validation in a larger population.

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