Mass Spectrometry-Based Proteomics for Classification and Treatment Optimisation of Triple Negative Breast Cancer

Triple-negative breast cancer (TNBC) presents a significant medical challenge due to its highly invasive nature, high rate of metastasis, and lack of drug-targetable receptors, which together lead to poor prognosis and limited treatment options. The traditional treatment guidelines for early TNBC are based on a multimodal approach integrating chemotherapy, surgery, and radiation and are associated with low overall survival and high relapse rates. Therefore, the approach to treating early TNBC has shifted towards neoadjuvant treatment (NAC), given to the patient before surgery and which aims to reduce tumour size, reduce the risk of recurrence, and improve the pathological complete response (pCR) rate. However, recent studies have shown that NAC is associated with only 30% of patients achieving pCR. Thus, novel predictive biomarkers are essential if treatment decisions are to be optimised and chemotherapy toxicities minimised. Given the heterogeneity of TNBC, mass spectrometry-based proteomics technologies offer valuable tools for the discovery of targetable biomarkers for prognosis and prediction of toxicity. These biomarkers can serve as critical targets for therapeutic intervention. This review aims to provide a comprehensive overview of TNBC diagnosis and treatment, highlighting the need for a new approach. Specifically, it highlights how mass spectrometry-based can address key unmet clinical needs by identifying novel protein biomarkers to distinguish and early prognostication between TNBC patient groups who are being treated with NAC. By integrating proteomic insights, we anticipate enhanced treatment personalisation, improved clinical outcomes, and ultimately, increased survival rates for TNBC patients.