Review Article: Probiotics-Mediated Enhancement of Checkpoint Inhibitor Blockade for HER2+ Breast Cancer

Immune checkpoint inhibitors (ICIs) have significantly improved survival rates for many types of cancer, giving patients survival prognoses that had been previously unattainable. Unfortunately, in many advanced cancers, including breast cancer (BC), objective response rates (ORRs) have been reported to be between 5% and 25% and immune-related adverse events (irAEs) can be severe, emphasizing the need to improve the effectiveness of ICIs while minimizing irAEs. In recent years, probiotics and various bacteria consortia have gained growing recognition for their application in immunotherapies for various cancers. Many preclinical models have demonstrated that probiotics significantly influence the gut microbiome, enhancing the production of beneficial metabolites and promoting interactions with cytotoxic T cells to amplify the antitumor effects of ICIs. For the treatment of HER2+ BC, current clinical trials have administered ICIs in combination with anti-HER2 agents (e.g., trastuzumab) to enhance treatment efficacy. Thus far, this combination has shown promising results, especially in patients with advanced PDL1-positive disease. However, as these trials are still ongoing, the efficacy of immune checkpoint blockade (ICB) therapy for HER2+ BCs remains inconclusive and requires further investigation. Thus, this review discusses the use of probiotics in ICB therapy, focusing on the potential role of probiotics in HER2+ BC response to ICIs, their underlying mechanisms and challenges.