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