Abstract P3-05-58: Frequency and prognosis of HER2-low status in Mexican patients with metastatic breast cancer

Abstract Background Breast cancer (BC) is the leading cause of cancer and cancer-related death in Mexican women. Recently, low expression of HER2 (HER2-low), defined as immunohistochemically 1+ or 2+ and lack of HER2 gene amplification, has gained increased attention as a promising new predictive biomarker for treatment with antibody-drug conjugates, such as trastuzumab-deruxtecan, not currently available in Mexico. To date, the frequency and prognostic value of HER2-low status in the Mexican population with metastatic BC remains unknown. Methods Single center retrospective cohort of patients diagnosed with metastatic BC between 2017 and 2020. Only patients with known HER2 status and available survival data were included. Patients’ sociodemographic and clinicopathological characteristics, and outcomes were collected from medical records. Descriptive statistics were used to analyze sociodemographic and clinicopathological characteristics. X2 tests were used to evaluate associations between HER2 status and other characteristics. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method and compared by the log-rank test according to HER2 status. Multivariable adjusted hazard ratios were estimated by Cox regression models. A p value of < 0.05 was considered statistically significant. Results Among 55 patients with metastatic BC, median age at diagnosis was 51 years, 56.4% were postmenopausal and 25.5% had family history of BC. The most frequent histologic subtype was ductal (65.5%), followed by lobular (20%). Approximately 2/3 presented with metastatic disease de novo (67.3%), 69.1% presented with visceral metastases and the median number of lines of treatment was 2. According to intrinsic subtypes 54.5% were luminal HER2-negative (HER2-), 16.4% luminal HER2-positive (HER2+), 10.9% HER2 enriched, and 18.2% triple negative. According to HER2 status, 11 (20%) were HER2+, 26 (47.3%) were HER2-low, and 18 (32.7%) were HER2-. HER2-low expression was more frequent in the hormone-receptor positive (HR+) (51.3%) than in HR negative (HR-) (31.3%), however, this difference was not statistically significant (p = 0.11). Patients’ characteristics according to HER2 status are shown in Table 1. With a median follow-up of 39.9 months, there were no differences in PFS and OS according to HER2 status. Median OS was 45, 30.8, and 46.4 months, for HER2+, HER2-low, and HER2-, respectively (p = 0.48). On univariate analysis, age, menopausal status, RH status, HER2 status, disease presentation and visceral metastases were not associated with improved OS. In patients with HER2-low status, median OS was 36.6 and 15.8 months for patients with HR+ and HR- disease (p = 0.009). In the HER2-low subgroup, multivariate analysis showed that HR status (hazard ratio 10.96 [95% CI 2.11-56.92], p = 0.004) and having received ≥2 lines of treatment (hazard ratio 13.34 [95% CI 1.97-90.37], p = 0.008) were statistically associated with better OS. Conclusion Our findings show that almost half of patients with metastatic BC have a low HER2 expression. Although HER2-low status did not impact survival in a small cohort of Mexican patients, HR status and lines of treatment were associated with better prognosis in patients with HER2-low disease. These results demonstrate the high burden of Mexican patients with HER2-low disease who could benefit from targeted therapies after first line therapy, and the importance of ensuring access to effective treatment options. Table 1. Patient characteristics. Citation Format: Bertha Alejandra Martinez-Cannon, Haydee Cristina Verduzco-Aguirre. Frequency and prognosis of HER2-low status in Mexican patients with metastatic breast cancer [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 P3-05-58.