PS2-13-14: Transformation of ER/PR Positive Invasive Ductal Carcinoma to Triple-Negative Metastatic Breast Cancer Following Adjuvant Abemaciclib: A Case Report

Abstract Abemaciclib is an oral CDK 4/6 inhibitor approved by the FDA in October 2021 for adjuvant treatment of HR-positive, HER-2 negative early breast cancer in combination with endocrine therapy (1). In the monarchE trial, 2 years of abemaciclib with endocrine therapy improved 5-year absolute invasive disease-free survival by 7.6% and distant relapse-free survival by 6.7% in high-risk, node positive patients (1). Findings A 45-year-old female was diagnosed with bilateral locally advanced IDC. Right breast biopsy showed ER 70%, PR 90%, HER2 0, Ki-67 90% (hot spots), and left breast biopsy showed ER > 90%, PR 5-10%, HER2 0, Ki-67 > 20%, both with Nottingham grade 3 (3+3+2=8) histology and bilateral axillary lymph node biopsies positive for macrometastatic carcinoma. Staging scans at diagnosis, including CT CAP and bone scan, were negative for distant metastasis. Genetic testing was negative. She was treated with 4 cycles of neoadjuvant dose dense AC-Taxol, then bilateral mastectomies, radiation, oophorectomy for ovarian suppression and letrozole for endocrine therapy. Given prior nodal involvement she began adjuvant abemaciclib six months after mastectomy. 8 months into abemaciclib treatment new bony metastases were incidentally found during imaging for pancreatitis. Bone scan confirmed new foci of increased uptake in C2/C3, T11, L4 and the left acetabulum concerning for osseous metastasis. Left acetabular core needle biopsy revealed metastatic adenocarcinoma consistent with known breast primary, ER positive (5%), PR negative (0%) and HER2 negative (1+). Given strong discrepancies between original strongly ER positive breast cancers and the bone metastases with low ER positivity of 5%, she underwent an FES PET which confirmed her osseous metastasis did not demonstrate any ER expression, further confirming change in the tumor’s ER status. Tempus testing revealed multiple inactionable pathogenic mutations, including two TP53 mutations (c.783-2A>C Splice region variant - LOF VAF: 59.8% and p.R267_N268delinsPD - c.800_802delinsCGG Missense variant - LOF VAF: 55%). A study by Corti et al. (2025) evaluated changes in HR status and recurrence among high-risk, HR-positive, HER2-negative early breast cancer treated with adjuvant abemaciclib plus endocrine therapy. Of 163 patients, 15 (9.2%) had recurrence during or shortly after completing abemaciclib (2). The median time to recurrence was 8 months. While half the recurrent tumors had strong ER positivity at time of diagnosis, on recurrence the biomarkers showed statistically significant changes in HR status, with ER positivity ≤10% and PR positivity < 1% on first recurrence. Most common recurrence sites were liver (40%), bone (26.7%), and lung (13.3%). Interestingly, the tumors with recurrence showed alterations in the p53 pathway and of those that had next genomic sequencing completed (n=10), alterations in p53 were found in 90% of the subset. Our goal is to highlight the transition of HR status after adjuvant abemaciclib as our case illustrates a unique presentation of disease recurrence. Further study should evaluate the frequency of new p53 mutations in patients treated with abemaciclib and its role in the transition of HR status. Rastogi P, O’Shaughnessy J, Martin M, et al. Adjuvant Abemaciclib Plus Endocrine Therapy for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative, High-Risk Early Breast Cancer: Results From a Preplanned monarchE Overall Survival Interim Analysis, Including 5-Year Efficacy Outcomes. J Clin Oncol 2024; 42:987-993 Corti C, Martin AR, Kurnia PT, et al. Clinicopathological features and genomics of ER-positive/HER2-negative breast cancer relapsing on adjuvant abemaciclib. ESMO Open. 2025 Jun 3;10(6):105126. doi: 10.1016/j.esmoop.2025.105126 Citation Format: A. Poles, S. Atluri, R. Rao. Transformation of ER/PR Positive Invasive Ductal Carcinoma to Triple-Negative Metastatic Breast Cancer Following Adjuvant Abemaciclib: A Case Report [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 PS2-13-14.