Biomarker profiling in triple-negative breast cancer

Triple-negative breast cancer (TNBC) is defined as breast cancer (BC) with an absence of oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) by immunohistochemistry (IHC). TNBC comprises up to 20% of all sporadic BCs. TNBC is a heterogeneous group of tumours with various distinct subtypes, each characterized by distinct genetic profiles, morphologies, and clinical courses. Patients with TNBC often present at a more advanced stage, with high risk of early relapse and poorer survival than non-TNBC subtypes. Attainment of a pCR is more common in TNBC and HER2-positive BC than in ER-positive BC, with the most significant association between pCR and survival observed in these aggressive subtypes. The role of immunotherapy in the treatment of early TNBC is evolving and is being evaluated in several clinical trials. Recent trials have shown that patients with TNBC may benefit from targeted immunotherapy – programmed cell death 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) – especially in tumours with high levels of tumour infiltrating lymphocytes (TILs) and PD-L1 overexpression. Expression of human endogenous retrovirus K (HERV-K) envelope protein (env) has been shown to be disproportionately increased in TNBC and is associated with poor outcome. The aims of this work are to investigate the prognostic value of several biomarkers including TILs, PD-L1 and HERV-K in TNBC, with respect to disease-free survival (DFS), metastasis-free survival (MFS), breast cancer-specific survival (BCSS) and pathological complete response (pCR) rates for patients diagnosed with TNBC at Galway University Hospitals (GUH) over a 20-year period.

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University of Galway

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Attribution-NonCommercial-NoDerivatives 4.0 International

cbn

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University of Galway Theses (PhD Theses)