How shall we treat early triple-negative breast cancer (TNBC): from the current standard to upcoming immuno-molecular strategies

Triple-negative breast cancer (TNBC) is a long-lasting orphan disease in terms of little therapeutic progress during the past several decades and still the standard of care remains chemotherapy. Experimental discovery of molecular signatures including the 'BRCAness' highlighted the innate heterogeneity of TNBC, generating the diversity of TNBC phenotypes. As it contributes to enhancing genomic instability, it has widened the therapeutic spectrum of TNBC. In particular, unusual sensitivity to DNA damaging agents was denoted in patients with BRCA deficiency, suggesting therapeutic benefit from platinum and poly(ADP-ribose) polymerase inhibitors. However, regardless of enriched chemosensitivity and immunogenicity, majority of patients with TNBC still suffer from dismal clinical outcomes including early relapse and metastatic spread. Therefore, efforts into more precise and personalised treatment are critical at this point. Accordingly, the advance of multiomics has revealed novel actionable targets including PI3K-Akt-mTOR and epidermal growth factor receptor signalling pathways, which might actively participate in modulating the chemosensitivity and immune system. Also, TNBC has long been considered a potential protagonist of immunotherapy in breast cancer, supported by abundant tumour-infiltrating lymphocytes and heterogeneous tumour microenvironment. Despite that, earlier studies showed somewhat unsatisfactory results of monotherapy with immune-checkpoint inhibitors, consistently durable responses in responders were noteworthy. Based on these results, further combinatorial trials either with other chemotherapy or targeted agents are underway. Incorporating immune-molecular targets into combination as well as refining the standard chemotherapy might be the key to unlock the future of TNBC. In this review, we share the current and upcoming treatment options of TNBC in the framework of scientific and clinical data, especially focusing on early stage of TNBC.