Abstract C015: Characterization of HER2-low breast tumors among a cohort of Colombian women

Abstract

Abstract Introduction: HER2-low expression tumors, either with weak or incomplete membrane expression (immunohistochemistry (IHC) 1+ or 2+ with negative in situ hybridization (ISH) result), are considered and treated as HER2-negative tumors. However, recent clinical trials have shown promising results in the application of antibody-drug conjugates (ADCs) for patients with HER2-low breast tumors, highlighting the need to characterize the clinical phenotype of this group. This is the first study in Colombia aiming to explore the clinical-pathological features and survival of women affected with HER2-low breast cancer, compared with HER2-negative (0+) and HER2-positive groups (2+ with ISH+ or 3+). Methods: We included 516 breast cancer patients from different health institutions in Colombia, diagnosed at clinical stages that ranged between I-III. Protein expression of HER2, Ki67, and hormone receptors (estrogen (ER) and progesterone (PR) receptor) was evaluated by IHC in a paraffin block with tumoral tissue by a single pathologist. We defined HER2 expression as positive (3+ or 2+ with positive ISH test), low (1+/2+ with negative ISH result), and negative (0+). We applied a Chi-square or Fisher’s exact test to evaluate clinical-pathological features for HER2-low cases, compared with HER2-negative (low vs. negative) and HER2-positive tumors (low vs. positive). Differences in overall survival (OS) and risk of mortality were assessed using the Kaplan-Meier and log-rang test, and a Cox proportional hazard model. Results: 325 cases (63%) were classified as HER2-negative, 97 (18.8%) as HER2-low, and 94 (18.2%) as HER2-positive. We encountered more clinical-pathological significant differences between HER2-low and HER2-positive tumors than with HER2-negative cases. A higher proportion of patients diagnosed after the age of 50 (79.4% vs. 62.4%, p=0.018), with better-differentiated tumors (Bloom Richardson II: 58.8 vs. 41.2%, p=0.025), and a lower proliferation index (Ki67 <20%: 50.5 % vs. 21.2%, p<0.001) was observed for HER2-low tumors, compared to the HER2-positive group; these characteristics were not significantly different between HER2-low and HER2-negative tumors. The proportion of ER-positivity was significantly higher in the HER2-low group, compared to both HER2-positive (89.7% vs. 62.4%, p<0.001) and negative groups (89.7% vs. 79.7%, p=0.039). Moreover, although longer OS rates were found in HER2-low patients, compared to the negative group (5.5 vs. 5.0 years, p=0.0032), the multivariate Cox model adjusted by ER status showed no statistically significant differences between these groups (HR=0.62, 95% CI, 0.34 – 1.13, p=0.122). Conclusions: HER2-low tumors represent an important proportion of all breast cancer cases diagnosed in Colombian women. Our results are consistent with other reports that show differences in ER expression between HER2-low tumors and both HER2-positive and negative subtypes, although it seems that the prognosis of HER2-low patients is not different than of the other groups. Citation Format: Laura Rey Vargas, Lina Maria Bejarano, Juan Carlos Mejia Henao, Diego Felipe Ballen Lozano, Maria Carolina Sanabria Salas, Silvia Juliana Serrano Gomez. Characterization of HER2-low breast tumors among a cohort of Colombian women [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C015.