Exceptional Response to Pembrolizumab in Metastatic ER+/HER2- Breast Cancer With Liver Metastases: A Case Report and Literature Review.

Background: Hormone receptor-positive (HR+) and HER2-negative breast cancer is the most common subtype in women, particularly in the postmenopausal setting. Unlike triple-negative breast cancer, the benefit of immune checkpoint inhibitors (ICIs) in HR+/HER2- disease remains uncertain because of low tumor immunogenicity and limited PD-L1 expression. Case Presentation: We describe a case of a 70-year-old woman who presented with severe anemia and was incidentally found to have a bleeding left breast mass. Biopsy confirmed Grade 3 invasive ductal carcinoma (ER+/PR+ > 95%, HER2-) with nodal involvement but no distant metastases, consistent with Stage IIIc disease. She was treated with neoadjuvant anastrozole, modified radical mastectomy, adjuvant chemotherapy, radiation, and continued endocrine therapy. After 3 years, she developed extensive hepatic metastases. Biopsy revealed ER+/PR-/HER2- disease with striking PD-L1 expression (CPS 95%). The disease progressed on fulvestrant and palbociclib, but switching to carboplatin, gemcitabine, and pembrolizumab led to rapid improvement: liver function normalized and imaging showed near-complete response within 3 months. This remission lasted about 10 months before disease progression and transition to hospice care. Conclusion: This case explains the potential role of ICIs in HR+/HER2- breast cancer with unusually high PD-L1 expression. It underscores the importance of biomarker-driven treatment and supports expanding PD-L1 testing to better identify patients who may benefit from immunotherapy in this traditionally resistant subtype.