Clinicopathological features and genomics of ER-positive/HER2-negative breast cancer relapsing on adjuvant abemaciclib

Background: Two years of adjuvant abemaciclib with endocrine therapy (ET) is standard for high-risk estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative, node-positive early-stage breast cancer. Relapse on adjuvant abemaciclib is poorly characterized. Patients and methods: Patients with recurrence on adjuvant abemaciclib at Dana-Farber Cancer Institute were identified. ER, progesterone receptor (PgR), and HER2 expression pre- and post-abemaciclib was determined, and the duration of adjuvant abemaciclib, ET, and first-line metastatic treatment recorded. Genomic alterations associated with ET and cyclin-dependent kinase 4 and 6 inhibitor resistance were analyzed if next-generation sequencing (NGS) was carried out at recurrence. Results: Among 163 patients who received adjuvant abemaciclib (2018-2024), 15 (9.2%) experienced recurrence. Median durations were 8.0 months [interquartile range (IQR) 3.8-21.2 months] for adjuvant abemaciclib, 18.5 months (IQR 7.0-23.0 months) for adjuvant ET, and 3.0 months (IQR 1.6-5.0 months) for first-line metastatic treatment. Among 12 patients with ER, PgR, and HER2 evaluable pre- and post-abemaciclib, 6 (50.0%) with strongly positive ER at diagnosis showed ER ≤10% and PgR <1% at recurrence. Of 10 patients with NGS at recurrence, 90% had P53 pathway alterations, with one ESR1 mutation and no RB1 mutations. Conclusions: In this series of patients relapsing on adjuvant abemaciclib plus ET, 50% showed ER loss, 90% had P53 pathway alterations, and median first-line metastatic treatment lasted 3 months.