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Title: Predictive modelling of short term outcomes following systemic neo-adjuvant and adjuvant therapy in breast cancer
Author: Randhawa, Sunreet Maneeta Kaur
ISNI:       0000 0004 7657 8837
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2018
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Chemotherapy in breast cancer is limited by a narrow therapeutic index. Toxicity from chemotherapy can be life threatening, henceforth biomarkers to predict side effects allowing treatment to be tailored for individual patients would enable improved patient outcomes. Side effects studied during this pilot study include neutropenia and subsequent complications, weight gain, fatigue and toxicity from all causes. Metabolites identified in each section not only offer the potential of a biomarker but also highlight perturbed physiological and metabolic pathways. Specifically, underlying mechanisms likely contributing to chemotherapy induced neutropenia are secondary to suppression of granulopoiesis by branched chain amino acid metabolites, altered cytotoxicity as a consequence of baseline inflammation and low baseline haematological results. Metabolites identified associated with weight gain indicate perturbations in energy expenditure pathways, which predispose and lead to weight gain during treatment. A metabolic framework generated from pre-treatment serum samples showed changes in fatty acids, glycerol, hypoxanthine and amino acids, reflecting perturbations in energy metabolism to be a major feature and causative factor in the development of chemotherapy related fatigue. In the study of all cause toxicity pre-treatment differences between fatty acids, ketones and branched chain amino acids predispose patients to development of greater toxicity and poorer QOL. This pilot study has identified several potential biomarkers that warrant future investigation.
Supervisor: Coombes, Charles ; Keun, Hector ; Holmes, Elaine Sponsor: BRC ; Merieux
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral