Spatial biomarkers of response to eribulin plus pembrolizumab in patients with metastatic triple negative breast cancer in the ENHANCE-1 trial

Abstract ENHANCE-1 was a phase Ib/II study which evaluated eribulin plus pembrolizumab as a treatment for metastatic triple negative breast cancer (mTNBC). All patients had measurable disease and up to 2 prior systemic treatments. We identified 142 patients with available samples and evaluated assoc...

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Main Authors: Yee Hoon Foong, Qi Wang, Matthew Kearney, Hortense Le, Hua Guo, Diane Chen, Michelle Garlin Politis, Courtney F. Connelly, Kevin Kalinsky, Rami S. Vanguri, Eileen P. Connolly
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:npj Breast Cancer
Online Access:https://doi.org/10.1038/s41523-025-00791-2
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Summary:Abstract ENHANCE-1 was a phase Ib/II study which evaluated eribulin plus pembrolizumab as a treatment for metastatic triple negative breast cancer (mTNBC). All patients had measurable disease and up to 2 prior systemic treatments. We identified 142 patients with available samples and evaluated associations between the pre-treatment tumor-immune microenvironment and response using diagnostic H&Es and multiplexed immunofluorescence with 2 antibody panels. Markers were chosen to evaluate lymphocytes and myeloid cells including: CD4, CD8, FoxP3, CD56, CD20, CD68, CD163, Vimentin, and HLA-DR. While H&E-assessed computational and manual assessments of stromal tumor infiltrating lymphocytes (sTILs) did not associate with response, multiplex immunofluorescence revealed several significant associations. These include enrichment of stromal CD56+ in non-responders and higher stromal CD4 + CD8+ in non-responders in breast samples. Responders exhibited higher stromal macrophage populations CD68 + , CD68+Vimentin + , CD68 + CD163+Vimentin+ as well as higher stromal HLA-DR + . Our results suggest that further studies on immune cell populations other than T-cells as predictive biomarkers for combination therapies in mTNBC are warranted.
ISSN:2374-4677