The Optimal Radioimmunotherapy Combinations for Advanced TNBC

Metastatic triple-negative breast cancer (mTNBC) is a particularly aggressive form of breast cancer that poses significant therapeutic challenges. Because mTNBC tumors do not express estrogen receptors (ER), progesterone receptors (PR), or HER2, patients with this subtype cannot receive benefits from endocrine therapy or HER2-targeted treatments, leaving chemotherapy as the main treatment option. However, the effectiveness of traditional chemotherapy drugs is limited and they often come with severe side effects. This leads to short durations of progression-free survival (PFS) and overall survival (OS), and the development of drug resistance, which can cause the cancer to recur and spread. Recently, the advent of immune checkpoint inhibitors has offered new therapeutic prospects for mTNBC. Inhibitors of PD-1/PD-L1, such as Pembrolizumab, Atezolizumab, and Toripalimab, have demonstrated some effectiveness in clinical trials, especially in patients with PD-L1-positive tumors. Yet, the overall response to immunotherapy remains low, and there is a risk of immune-related adverse events (irAEs), which require vigilant monitoring. To address the shortcomings of both chemotherapy and immunotherapy, researchers are investigating innovative treatment strategies. These include targeting additional immune checkpoint molecules within the tumor microenvironment, developing novel chemotherapy drugs, and integrating immunotherapy with other treatments like radiotherapy. Local radiotherapy can substantially stimulate the immune system, increasing the antigenicity of cancer cells and enhancing the ability of cytotoxic T lymphocytes to recognize and attack cancer cells. Although combined radiotherapy and immunotherapy have shown promise in treating other types of cancer, the most effective combination patterns, optimal radiotherapy dosing schedules, and the most suitable patient groups for advanced breast cancer, particularly mTNBC, are not well defined. This study seeks to identify the best combinations of radiotherapy and immunotherapy for advanced breast cancer, with the aim of improving survival rates and setting new standards for treatment.