Time-of-day administration of immune checkpoint inhibitors: current clinical evidence and future directions for breast cancer.

Abstract

Purpose of review: Immune checkpoint inhibitors (ICIs) are increasingly used in breast cancer, particularly in triple-negative breast cancer. This review summarizes the biologic rationale and emerging clinical evidence for time-of-day ICI administration and discusses its implications for breast cancer.

Recent findings: Circadian rhythms provide a biologic rationale for time-dependent immunotherapy efficacy. Several retrospective studies across multiple tumor types have suggested associations between earlier ICI administration and improved outcomes, although findings remain inconsistent. Breast cancer-specific data are expanding but remain heterogeneous, with signals varying by treatment setting, endpoint, timing definition, and tumor immune contexture. These findings suggest that treatment timing should be interpreted in the context of the broader treatment platform in which immunotherapy is delivered, including concomitant chemotherapy and supportive medications, as well as host circadian state and tumor immune contexture. An ongoing prospective study aims to integrate circadian, systemic immune, and tumor-based assessments to elucidate the biological and clinical relevance of treatment timing in breast cancer.

Summary: Current evidence does not establish an optimal infusion window for breast cancer treatment. Prospective studies integrating clinical outcomes with circadian, systemic immune, and tumor-based analyses are needed to determine whether treatment timing can be developed into a biologically informed strategy.