Chemotherapeutics as immune modulators for the treatment of triple-negative breast cancer

Breast cancer is the second leading cause of cancer death in women. Among its various subtypes, triple-negative breast cancer (TNBC) is an aggressive form characterised by the absence of hormone receptor expression and lack of HER2 amplification, which severely limits treatment options. While some targeted therapies exist, chemotherapy remains the primary treatment for TNBC. Interestingly, despite TNBC patients showing the highest initial response rates to chemotherapy, they also experience the lowest overall survival. This phenomenon is often referred to as the “TNBC paradox,” which makes achieving curative outcomes incredibly challenging due to the unpredictable nature of the disease. This highlights a significant unmet clinical need to develop tailored medicine approaches to maximise patient response. Unlike other breast cancer subtypes, TNBC is considered “immune hot,” meaning it has a higher presence of immune cells within the tumour microenvironment. This characteristic has made the development of immunotherapies a major focus of research. PD-1/PD-L1 checkpoint inhibitors have already become the standard of care for high-risk early stage TNBC patients, and other immunomodulatory therapies, such as therapeutic vaccines, are currently under investigation. Given that chemotherapy is still the cornerstone of TNBC treatment, understanding its impact on systemic and tumour immune cells is crucial for improving the effectiveness of combination therapies. This review will delve into the specific roles of TNBC chemotherapies on key immune cells during both tumour progression and regression.