Abstract P1-04-17: Clinical and pathological differences between HER2 Low and other cancer subtypes in breast cancer patients

Abstract Background: HER2 is a tyrosine kinase receptor belonging to the human epidermal receptor family and is considered an important proto-oncogene in the biology of breast carcinoma. HER2 overexpression is determined by a +3 score on the immunohistochemistry (IHC) assay. In addition, tumors with IHC results of +1 or +2 with ISH negative were defined as HER2-low. Recent studies have shown that the clinicopathological characteristics of HER2-low tumors, pointing out potential differences regarding hormone receptor status and new treatment possibilities in this patients. Objective: To assess the frequency and clinicopathological differences between cancer subtypes, as well as the survival of these patients. Methods: All patients with breast cancer diagnosed between 1987 and 2021 included in the Pérola Byington Hospital database were eligible. Patients were excluded if they had bilateral disease, had participated in clinical studies, or had incomplete data. The primary endpoint was overall survival stratified by cancer subtype, secondary endpoints were clinicopathological differences between cancer subtypes and death probability. Both the t-test and the chi-square test were used to analyze the association of each variable between the groups. Multivariate analysis was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for the death outcome. Cox regression was used for survival analysis, with the Log-rank method and the results were presented in a survival graph using the Kaplan-Meier method. The R software version 4.1.1 was used to perform all analyzes, with a p-value < 0.05 being considered statistically significant. Results: 11,234 patients were included: 4,541 (40.42%) had Luminal cancer subtype, 2,955 (26.30%) HER2 Low, 2,242 (19.96%) triple negative, and 1,496 (13.32%) HER2 overexpression. Age, self-reported ethnicity, BMI, presence of comorbidities, clinical stage, nuclear grade, histological grade, family history, radiotherapy, chemotherapy, surgery, local, and systemic recurrence, and death showed statistically significant differences between cancer subtypes (table 1). In the multivariate regression (adjusted for the other evaluated characteristics), patients with HER2 overexpression cancer subtype showed a 44.8% greater probability of death than patients with HER2 Low (OR 1.448, 95%CI 1.046-2.004, p=0.026), while the patient with triple-negative cancer had a 26.1% lower probability of evolving to death when compared to the HER2 Low patient (OR 0.739, 95%CI 0.562-0.969, p=0.0229). The luminal subtype showed no statistically significant difference when compared to the patient with HER2 Low. Overall survival showed a statistically significant difference between cancer subtypes, with a median of 12 years for Luminal HR 0.816 (0.73-0.913), 15 years for HER2 overexpression HR 1.154 (1.003-, 327), and no statistical difference for triple negative HR 0.978 (0.859-1.114) compared to 12 years for HER2 Low. Conclusion: This study in breast cancer patients demonstrates significant differences between cancer subtypes, with a higher probability of progression to death for patients with HER2 overexpression, while patients with Luminal subtype had a lower probability, when compared with HER2 Low. More studies are needed to clarify the impact of these differences between cancer subtypes on response to therapy. Association between cancer subtype and other variables (n=11,234). Citation Format: ANDRE MATTAR, Andressa Amorim, Marina Diogenes, Jorge Shida, Luiz Henrique Gebrim. Clinical and pathological differences between HER2 Low and other cancer subtypes in breast cancer patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-04-17.