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.