Cellular and molecular mechanisms of response to, and recurrence following, breast radiotherapy
type: CreativeWork
description: This thesis explores response to, and recurrence following, radiotherapy in primary breast cancer within three clinical trials investigating aspects of radiation management: the IMPORT trials, IMPORT LOW and IMPORT HIGH, and the NeoRT trial. Clinical outcomes from the NeoRT trial are described as well as the results of translational analyses of patient samples from all 3 trials, aiming to interrogate genomic aspects of radiotherapy response and of recurrence following breast conserving surgery and radiotherapy. Ipsilateral breast tumour recurrences following breast conserving treatment have long been noted to predominantly occur in or close to the tumour bed from which the index cancer was removed with a smaller number arising in other quadrants of the breast. A widely held hypothesis is that breast cancer local recurrence after partial breast radiotherapy usually represents ‘true recurrence’ – i.e. derived from residual cells of the index cancer - if arising within the quadrant of the original tumour, and an independently arising new primary cancer if arising beyond this index quadrant or in the contralateral breast. The IMPORT trials are both large UK randomised controlled trials investigating the paradigm of adapting radiotherapy dose/fractionation and volume to the spatially varying risk of recurrence across the breast. Partial breast radiotherapy is investigated in a cohort at low risk of local recurrence in IMPORT LOW. Simultaneous integrated boost to two dose escalation levels is compared to a control of sequential radiotherapy boost in a cohort at higher risk of local recurrence in the sister trial, IMPORT HIGH. This work analyses the genomic, spatial and clinicopathological relationships between paired index and subsequent tumours within the two trials, aiming to answer the following questions: 1) Can the Breakclone methodology, which integrates analysis of shared and private mutations and copy number abnormality breakpoints in tumour pairs as well as cohor…
abstract: This thesis explores response to, and recurrence following, radiotherapy in primary breast cancer within three clinical trials investigating aspects of radiation management: the IMPORT trials, IMPORT LOW and IMPORT HIGH, and the NeoRT trial. Clinical outcomes from the NeoRT trial are described as well as the results of translational analyses of patient samples from all 3 trials, aiming to interrogate genomic aspects of radiotherapy response and of recurrence following breast conserving surgery and radiotherapy. Ipsilateral breast tumour recurrences following breast conserving treatment have long been noted to predominantly occur in or close to the tumour bed from which the index cancer was removed with a smaller number arising in other quadrants of the breast. A widely held hypothesis is that breast cancer local recurrence after partial breast radiotherapy usually represents ‘true recurrence’ – i.e. derived from residual cells of the index cancer - if arising within the quadrant of the original tumour, and an independently arising new primary cancer if arising beyond this index quadrant or in the contralateral breast. The IMPORT trials are both large UK randomised controlled trials investigating the paradigm of adapting radiotherapy dose/fractionation and volume to the spatially varying risk of recurrence across the breast. Partial breast radiotherapy is investigated in a cohort at low risk of local recurrence in IMPORT LOW. Simultaneous integrated boost to two dose escalation levels is compared to a control of sequential radiotherapy boost in a cohort at higher risk of local recurrence in the sister trial, IMPORT HIGH. This work analyses the genomic, spatial and clinicopathological relationships between paired index and subsequent tumours within the two trials, aiming to answer the following questions: 1) Can the Breakclone methodology, which integrates analysis of shared and private mutations and copy number abnormality breakpoints in tumour pairs as well as cohor…
author: Lightowlers, Sara
keywords: breast radiotherapy, tumour evolution, local recurrence
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/eed9bee3-7107-49b0-a0de-14be335b4600/download
license: http://purl.org/NET/rdflicense/allrightsreserved
date published: 2025-01-06
date modified: 2026-07-22T22:24:23Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.120027