ArticleCancers2026
Basal-like Phenotype Identifies Immunotherapy-Responsive Subset of HR+/HER2- Breast Cancer with Aggressive Clinical Behavior.
Article in Cancers, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundWhile basal-like markers (BMs), particularly cytokeratin 5/6 (CK5/6) and epidermal growth factor receptor (EGFR), are traditionally associated with triple-negative breast cancer, their expression in HR+/HER2- tumors defines a clinically distinct subgroup with unique therapeutic vulnerabilities. We comprehensively characterized the clinicopathological features, immune microenvironment, and neoadjuvant immunotherapy response of BM-positive HR+/HER2- breast cancer.
methodsWe analyzed 150 basal marker-positive (BM+) and 180 BM-negative HR+/HER2- breast cancer patients. Clinicopathological data and survival outcomes were assessed using Kaplan-Meier and Cox regression analyses. The immune microenvironment was characterized by stromal tumor-infiltrating lymphocytes (sTILs) and immunohistochemistry for immune markers (CD3, CD8, FOXP3, CXCL13, CD68, PD-1, PD-L1). An independent cohort of 53 BM+ patients receiving neoadjuvant chemotherapy with anti-PD-1/PD-L1 immunotherapy was evaluated for pathological complete response (pCR).
resultsBM+ patients exhibited significantly more aggressive features: younger age at diagnosis, higher histological grade, increased necrosis, and lower hormone receptor expression. BM+ status independently predicted worse disease-free survival (HR = 1.96,
conclusionsThe basal-like phenotype identifies a clinically aggressive subset of HR+/HER2- breast cancer with distinct immune-activated characteristics and remarkable immunotherapy response rates. These findings suggest that the BM status, particularly CK5/6 expression, may serve as a basis for clinicians to decide whether to administer immunotherapy to patients with HR+/HER2-breast cancer.
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