Abstract PS3-08-02: Impact of Hormone Receptor-Positive Breast Cancer Subtypes on Oral Endocrine Therapy Adherence and Persistence

Abstract Introduction: Hormone receptor-positive (HR+) breast cancer accounts for approximately 78% of cases in the U.S. and is primarily treated with adjuvant oral endocrine therapy (AOET) to reduce recurrence and improve survival. HR+ tumors are further classified into molecular subtypes—luminal A and luminal B—based on hormone receptor expression, Ki-67 proliferation index, and HER2 status, which together guide treatment intensity and strategy. Despite the established benefits of AOET, adherence and persistence remain suboptimal, with up to 50% of patients discontinuing therapy prematurely, increasing the risk of recurrence and mortality. Although side effects and comorbidities are known barriers, limited research has examined how these factors vary by subtype. Understanding these relationships is essential to developing targeted adherence interventions for HR+ breast cancer survivors. Objective: To assess the association between HR+ breast cancer subtypes (luminal A, B, and HER2) and AOET adherence and persistence, and examine the impact of sociodemographic and clinical factors. Methods: This retrospective chart review included patients diagnosed with stage I-III hormone receptor-positive (HR+) breast cancer in 2014 at Rush University Medical Center who were prescribed adjuvant oral endocrine therapy (AOET). Of 391 patients identified through the Rush Cancer Registry, 133 met eligibility criteria after exclusions for stage 0, IV, or unknown; insufficient documentation; or transfer of care. Molecular subtypes were classified as luminal A, luminal B, luminal HER2, or mixed, based on hormone receptor, HER2, and Ki-67 status. Oncotype recurrence scores were available for a subset. Clinical variables, comorbidities, and sociodemographic factors—including age and race/ethnicity—were recorded. Adherence and persistence were assessed by AOET duration, completion of ≥5 years of therapy, and documentation of adherence behaviors, side effects, and reasons for discontinuation. Statistical analyses included descriptive and inferential tests to evaluate associations between subtype, sociodemographic and clinical factors, and adherence outcomes. Results: Among 133 patients, 35% had luminal A, 19% luminal B, 5% luminal HER2, and 29% mixed-subtype tumors. Although AOET duration appeared longer in luminal A compared to other subtypes, these differences were not statistically significant. Receipt of chemotherapy was significantly associated with shorter AOET duration (p = 0.042), suggesting treatment intensity may influence persistence. Consistent with prior studies, patients who reported endocrine-related side effects were significantly more likely to discontinue therapy early (p = 0.026) and were less likely to take AOET as prescribed (p = 0.005 for multi-level adherence; p = 0.003 for binary adherence). Oncotype recurrence scores also differed significantly by subtype (p < 0.001), though scores were not routinely calculated in HER2+ or mixed-subtype patients. Conclusion: Molecular subtype was not a statistically significant predictor of AOET adherence or persistence in this cohort. However, treatment-related side effects and chemotherapy exposure were significantly associated with reduced persistence and nonadherence. While the link between side effects and endocrine nonadherence is well established, our findings confirm that this relationship persists across diverse subtypes and real-world practice settings. These results underscore the need for survivorship strategies that address symptom burden and treatment intensity, especially for patients receiving multimodal therapy. Future work should explore how subtype-specific treatment planning may inform adherence interventions in HR+ breast cancer. Citation Format: W. S. Hercule, J. O. Dorcelien, M. A. Allen, L. Anoruo, C. Ikedi, T. Pham, M. L. Barbosa, T. N. Christ, R. Rao. Impact of Hormone Receptor-Positive Breast Cancer Subtypes on Oral Endocrine Therapy Adherence and Persistence [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 PS3-08-02.