Abstract PS1-11-23: Clinicogenomic Features of Recurrence After Adjuvant Abemaciclib in HR+/HER2- Early Breast Cancer

Abstract Background: Adjuvant abemaciclib combined with endocrine therapy is approved for patients with high-risk hormone receptor-positive (HR+), HER2-negative early breast cancer. However, recurrence still occurs in a subset of patients, and the clinical and molecular features associated with early relapse are not well characterized. Methods: We identified patients who were treated with adjuvant abemaciclib at Memorial Sloan Kettering (MSK) from April 2019 to February 2024 whose disease subsequently recurred. Clinicopathologic and tumor next-generation sequencing data (MSK-IMPACT) were abstracted from patient records. Changes in hormone receptor expression and genomic alterations between primary and recurrent samples were evaluated. Results: Among 334 patients treated with adjuvant abemaciclib, 18 (5.4%) developed recurrence. Baseline clinicopathologic and treatment characteristics are summarized in Table 1. Median time from surgery to abemaciclib initiation was 5.8 months (range 2.0-18.8), and from abemaciclib initiation to recurrence was 14.2 months (2.4-43.7). Median duration of abemaciclib therapy was 12.6 months (0.5-34.6); discontinuation was due to disease progression (14; 77.8%), toxicity (2; 11.1%), therapy completion (1; 5.6%), or early switch to olaparib (1; 5.6%). 16 patients (88.9%) had distant metastases and 2 (11.1%) had locoregional/chest wall recurrence. Median duration of first-line metastatic therapy was 4.0 months (1.5-9.0), including 5 patients still on therapy at the time of data abstraction. Among 17 cases with paired immunohistochemistry data, ER expression declined in 11 (64.7%), with a median absolute decrease of 65% (range 9-95%), including complete loss in 4 tumors (23.5%). PR declined in 15 (88.2%), with a median absolute decrease of 20% (range 1-99), and complete loss in 13 (76.5%). Patients with ≥50% ER loss (8, 47.1%) had a median time to abemaciclib recurrence of 13.1 months, compared to 15.0 months in those with 50% loss (3, 17.6%) and 16.8 months in those with no loss (6, 35.3%). HER2 IHC increased in 8 tumors (47.1%), decreased in 3 (17.6%), and was unchanged in 6 (35.3%). Germline testing was available in 16/18 patients; 4 (25%) had pathogenic variants (BRCA2, n=2; PALB2, n=1; RAD51D, n=1). Tumor NGS findings from matched primary-recurrence pairs (n=6) and unmatched recurrence-only samples (n=8) are summarized in Table 1. Conclusions: In this cohort, recurrence after adjuvant abemaciclib occurred in 5.4% of patients and was characterized by frequent hormone receptor loss and enrichment of alterations associated with endocrine and CDK4/6 inhibitor resistance, including RB1, PTEN, and MYC, as well as targetable alterations such as PIK3CA and BRCA2. These findings highlight the potential value of molecular profiling earlier in the treatment course to assess risk of relapse in high-risk early-stage disease. Updated data will be presented at the meeting. Citation Format: J. Teysir, E. Kohilakis, D. Audi Blotta, Y. Sallah, S. Shen, C. Dang, K. Jhaveri. Clinicogenomic Features of Recurrence After Adjuvant Abemaciclib in HR+/HER2- Early Breast Cancer 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 PS1-11-23.