Abstract PS2-06-15: Population-based outcomes and patterns of care for patients with stage I-III, HER2-negative breast cancer, by estrogen receptor expression levels: a high-resolution study

Abstract Background HER2-negative breast cancer (BC) encompasses a wide range of estrogen receptor (ER) expression levels. Currently, tumors are classified as ER-positive if at least 1% of tumor cells express ER. However, outcomes vary significantly across this spectrum. Notably, ER-low tumors (ER 1-9%) have been associated with outcomes as poor as those observed in triple-negative breast cancer (TNBC, ER 0%). Despite this heterogeneity, few population-based studies have systematically assessed outcomes across the continuum of ER expression, while accounting for treatment details and tumour characteristics. To address this gap, we analyzed a large, population-based cohort of women diagnosed with stage I-III, HER2-negative BC. Methods We used a high-resolution dataset of individual-level records from the Veneto Tumour Registry, a large population-based cancer registry in Italy. Information on stage, ER levels, grade, and Ki67 was collected. Patient-level data on surgery, chemotherapy (CT), and endocrine therapy (ET) were retrieved from population-based prescription repositories and claims. Patients were stratified by ER level expression: 0% (TNBC), 1-9% (ER-low), 10-49%, and ≥50%. Eligible CT treatments were those given within 12 months before or after surgery. Eligible endocrine treatments included letrozole, anastrozole, exemestane, or tamoxifen following surgery. We estimated cancer-specific survival by ER category, up to six years after diagnosis, using validated cause of death data. Results The study population included 3,771 patients 18 years of age or older, diagnosed with stage I-III, HER2-negative BC between 2017 and 2021, with follow-up until December 31, 2024. The majority of patients (77.8%) were aged 50 years or older. Stage I tumours accounted for 60.9% of cases, while stage II and III tumours made up 31.4% and 7.6%, respectively. ER expression levels were as follows: 6.9% of patients had TNBC, 1% had ER-low, 1.6% had ER 10-49%, and 90.5% had ER ≥50%. Most tumors were grade 1 or 2 (75.4%), and 63.2% had a Ki67 index below 20%. Among patients with an ER level ≥1%, ET was given to 23.7% of those with ER-low, 79% with ER 10-49%, and 89.7% with ER ≥50%. ET discontinuation within the first year remained below 10% across all groups. CT was received by 79.9% of patients with TNBC, 81.6% with ER-low BC, 59.7% with ER 10-49%, and 29.5% with ER ≥50%. Three-year cancer-specific survival was 90.2% for TNBC, 90.5% for ER-low, 94.6% for ER 10-49%, and 98.4% for ER ≥50%. At six years post-diagnosis, survival declined to 85% for patients with TNBC, stabilized around 90% for both ER-low and ER 10-49% groups, and remained above 95% in the ER ≥50% group. Conclusion To our knowledge, this is one of the largest population-based studies to report outcomes and cancer care patterns in patients with HER2-negative early BC across the full spectrum of ER expression, treated in real-world clinical practice. Our findings highlight that survival varies by ER expression level and over time. Patients with TNBC or ER-low BC showed similarly poor short-term outcomes. Over the longer term, survival in the TNBC group declined steadily, whereas trajectories for the other subgroups, including ER-low, were less steep. The 5% absolute difference in six-year cancer-specific survival between TNBC and ER-low BC may suggest a modest benefit associated with ET, which was received by up to one-quarter of patients in the ER-low group. However, the small sample size in this subgroup limits definitive conclusions. Larger, high-resolution, population-based studies with long follow-up are needed to validate the impact of real-world treatment practices and inform cancer care. Citation Format: F. Girardi, S. Guzzinati, M. V. Dieci, P. Napolitano, L. Dal Maso, F. Puglisi, V. Guarneri, M. Zorzi. Population-based outcomes and patterns of care for patients with stage I-III, HER2-negative breast cancer, by estrogen receptor expression levels: a high-resolution study 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 PS2-06-15.