Triple-negative breast cancer (TNBC) is considered one of the most aggressive forms of breast cancer with poor survival rates compared to other breast cancer subtypes. TNBC is characterized by the absence of the estrogen receptor alpha, progesterone receptor, and the human epidermal growth factor receptor 2, limiting those viable treatment options available to patients with other breast cancer subtypes. Furthermore, due to the particularly high heterogeneity of TNBC, conventional treatments such as chemotherapy are not universally effective, leading to drug resistance and intolerable side effects. Thus, there is a pressing need to discover new therapies beneficial to TNBC patients. This review highlights current findings regarding the roles of three steroid hormone receptors, estrogen receptor beta, the androgen receptor, and the glucocorticoid receptor, in the progression of TNBC. In addition, we discussed several ongoing and completed clinical trials targeting these hormone receptors in TNBC patients.

Triple-negative breast cancer (TNBC) remains a significant challenge in oncology, contributing to a significant portion of cancer-related deaths among women. Current therapeutic options, including chemotherapy, surgery, radiation, and hormonal targeting therapies, exhibit limited efficacy, necessitating the exploration of innovative treatment modalities. The emergence of drug resistance and the persistence of cancer stem cells (CSCs) further emphasize the urgent need for novel therapeutic strategies. In this context, natural killer cell-derived extracellular vesicles (NK-EVs) have emerged as a promising cell-free therapeutic approach that exhibits high tumor infiltration and cytotoxicity against cancer cells and CSCs. This study aims to investigate the efficacy of NK-EVs as a therapeutic strategy for TNBC using various clinically relevant models, including patient-derived xenografts. Pathway analysis suggests strong activation of apoptosis via canonical caspase activation, as well as necrosis, thereby confirming the important cytotoxic effect of NK-EVs. Interestingly, NK-EVs were also found to suppress TNBC CSCs by disrupting their functionality and viability, and NK-EV treatment increased the expression of apoptosis markers in both CSCs and non-CSCs. By elucidating the therapeutic efficacy and translational potential of NK-EV-based interventions in TNBC, these findings offer critical insights for the development of future immunotherapeutic strategies against this aggressive subtype of breast cancer.