Challenges in the combination of radiotherapy and immunotherapy for breast cancer

ABSTRACT

Introduction

Immunotherapy (IT) is showing promise in the treatment of breast cancer, but IT alone only benefits a minority of patients. Radiotherapy (RT) is usually included in the standard of care for breast cancer patients and is traditionally considered as a local form of treatment. The emerging knowledge of RT-induced systemic immune response, and the observation that the rare abscopal effect of RT on distant cancer metastases can be augmented by IT, have increased the enthusiasm for combinatorial immunoradiotherapy (IRT) for breast cancer patients. However, IRT largely follows the traditional sole RT and IT protocols and does not consider patient specificity, although patients’ responses to treatment remain heterogeneous.

Areas covered

This review discusses the rationale of IRT for breast cancer, the current knowledge, challenges, and future directions.

Expert opinion

The synergy between RT and the immune system has been observed but not well understood at the basic level. The optimal dosages, timing, target, and impact of biomarkers are largely unknown. There is an urgent need to design efficacious pre-clinical and clinical trials to optimize IRT for cancer patients, maximize the synergy of radiation and immune response, and explore the abscopal effect in depth, taking into account patients’ personal features.

KEYWORDS:

• Immunotherapy
• radiotherapy
• breast cancer
• immune response
• abscopal effect
• precision medicine

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by the American Cancer Society under Grant no. RSG-22-030-01-CTPS, Louisiana State University Faculty Research Grant, Louisiana Board of Regents Research Competitiveness Subprogram, and a Pilot Research Award from the Center for Pre-Clinical Cancer Research (Cancer COBRE, P20GM135000, funded by the National Institutes of Health) at Louisiana State University.