The Promise of Immunotherapy for Breast Cancer Brain Metastases
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Purpose of Review
The goal of our review is to describe the rationale for immunotherapy in the treatment of breast cancer brain metastases (BCBM), the current landscape of clinical trials for this disease process, and possible future directions based on anticipated results.
Immune checkpoint inhibition has shown efficacy in the treatment of several solid tumor brain metastases (i.e., melanoma and non-small cell lung cancer), but data specific to BCBM is relatively sparse. Preclinical studies in BCBM have illustrated a lower immune content in the brain microenvironment measured by tumor-infiltrating lymphocytes (TILs) in brain metastases compared to primary tumors. Yet, improved outcomes are associated with higher TIL content in the BCBM, and strategies to understand and alter the complex brain immune microenvironment are needed.
Summary of Findings
Based on observations in the non-breast cancer setting and early results in advanced breast cancer, it is likely that novel, strategic combination immunotherapy strategies will be needed to yield meaningful outcomes for BCBM patients. Some exciting concepts underway include novel immunotherapy combinations, concurrent stereotactic radiosurgery, bi-specific antibody armed activated T cells, and HER2-chimeric antigen receptor T cells for leptomeningeal disease.
KeywordsBreast cancer Brain metastases Central nervous system Tumor-infiltrating lymphocytes Immunotherapy
Compliance with Ethical Standards
Conflict of Interest
Sarah Sammons reports receiving research funding from Astra Zeneca and Eli Lilly. Carey Anders reports work with PUMA, Lilly, Merck, Seattle Genetics, Nektar, Tesaro, G1-Therapeutics, Genentech, Eisai, IPSEN, UpToDate, and Jones and Bartlett during the conduct of the study. Amanda Van Swearingen declares no conflicts of interest relevant to this manuscript.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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