Abstract PS4-08-30: Prognostic evaluation of HER2-low status in patients with early breast cancer who underwent neoadjuvant chemotherapy

Abstract Introduction: In the last few years, several studies have highlighted the prognostic and therapeutic implications concerning the heterogeneity of HER2 expression in breast cancer (BC). In the metastatic setting, antibody-drug-conjugates (ADCs) targeting HER2 are approved for patients with low HER2 expression and showed overall survival benefit. In the early setting, however, the role of HER2 low is still under investigation. We aim to determine if HER2 low tumors show differences in pathological complete response rates (pCR) after neoadjuvant chemotherapy (NCT) and survival outcomes when compared to HER2 zero tumors. Methods: Retrospective cohort in Hospital de Clínicas de Porto Alegre, an academic hospital in the South of Brazil. Inclusion criteria: adult patients with stage I-III invasive BC who underwent neoadjuvant chemotherapy and surgery between 2010 and 2020. Patients with HER2 overexpression, unknown or inconclusive HER2 status were excluded. HER2 low was classified as 1+ on immunohistochemistry (IHC) or 2+ on IHC without amplification in the Silver-enhanced in situ hybridization (SISH), while HER2 negative was characterized as 0+ on IHC. Main outcomes: 1) pCR rates in the breast and axilla, comprising absence of invasive residual disease (in situ carcinoma allowed); 2) recurrence-free survival (RFS), defined as the time to distant or local recurrence; 3) overall survival, defined as the time to death due to any cause. Results: N = 173 female patients with a mean (standard deviation) age of 49.24 (10.41) years. Median (interquartile range) follow up: 5.69 (4.71) years. Menopausal status: 89 (51.44%) premenopausal. Stage at diagnosis: 55 (31.8%) stage II and 117 (67.63%) stage III. Hormonal receptors (HR) were positive in 121 (69.94%) patients. NCT comprised an anthracycline-based regimen in 167 (96,50%) patients. HER2 status: 88 (50.87%) HER2 low and 85 (49.13%) HER2 zero. HER2 low patients had a higher frequency of positive HR than HER2 zero patients (82.96 vs. 56.47% respectively, Chi square P 0.001). pCR rates were 15.61% in the whole sample, 10.23% in HER2 low and 21.18% in HER2 zero patients; however, statistical significance was not reached (Chi square P = 0.076). RFS rate was 67.05% in 5 years and 61.27% in 10 years, with no difference in RFS between HER2 low and HER2 zero patients (Hazard ratio HR 0.91, 95% Confidence Interval CI 0.56 - 1.47, P = 0.702). OS rate was 70.52% in 5 years and 65.32% in 10 years, also with no difference between HER2 low and zero (HR 0.64, 95% CI 0.39 to 1.08, P = 0.092). Conclusion: In our study, HER2 low and zero patients appeared to have similar pCR and survival rates. More studies concerning HER2 status in the early BC setting should be conducted in order to verify possible differences in oncological outcomes which may change clinical practice. Furthermore, the definition of HER2 low is quite arbitrary and could benefit from revision. Citation Format: S. Giusti Alves, M. Silveira Graudenz, G. Vasconcelos Alves, C. Pimentel Oppermann, J. Basso, M. Morás, L. Gonçalves de Oliveira, G. Luís França Rêgo, A. Lopes Silva, E. de Farias Barra, V. Cristina Rodrigues Borges, A. Baggio Pereira, D. Dornelles Rosa. Prognostic evaluation of HER2-low status in patients with early breast cancer who underwent neoadjuvant chemotherapy abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-08-30.