Genome-wide association study of acute toxicity and quality of life in breast cancer patients treated by surgery and radiotherapy in the REQUITE cohort study


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Tim Rattay1,Colin Veal1,David Azria2,Jenny Chang-Claude3,Susan Davidson4,Alison M Dunning5,Dirk de Ruysscher6,Sara Gutierrez-Enriquez7,Philippe Lambin8,Anusha Müller3,Tiziana Rancati9,Barry S Rosenstein10,Petra Seibold3,Elena Sperk11,R Paul Symonds1,Riccardo Valdagni9,Ana Vega12,Liv Veldeman13,Adam Webb1,Catharine West14,Christopher J Talbot1,On behalf of the15
1University of Leicester, Leicester, UK,2 Institut du Cancer Montpellier (ICM), Montpellier, France,3German Cancer Research Center (DKFZ), Heidelberg, Germany,4The Christie Hospital NHS Foundation Trust, Manchester, UK,5University of Cambridge, Cambridge, UK,6University Hospitals Leuven, KU Leuven, Leuven, Belgium,7Vall d’Hebron Institute of Oncology, Barcelona, Spain,8MAASTRO Clinic, Maastricht, Netherlands,9 Istituto di Ricovero e Cura a Carattere Scientifico, Fondazione Istituto Nazionale dei Tumori Milan, Milan, Italy,10Icahn School of Medicine at Mount Sinai, New York, US,11University Medical Centre Mannheim, Heidelberg, Germany,12Fundacion Publica Galega Medicina Xenomica, A Coruña, Spain,13Universiteit Ghent, Ghent, Belgium,14University of Manchester, Manchester, UK,15REQUITE Study, Leicester, UK

Abstract

Background

Clinically significant side-effects from radiotherapy following surgery affect around a quarter of breast cancer patients and may adversely affect breast cosmesis and quality of life (QoL).  If patients at high risk of local treatment toxicity could be identified at breast cancer diagnosis, this could be taken into account when discussing treatment options.  Genome wide association studies (GWAS) have facilitated discoveries in complex-trait genetics, biology of disease and translation towards new therapeutic interventions.  In the field of radiogenomics, several genetic associations have been replicated to date but the majority have been in relation to late toxicity. 

Method

Breast cancer patients (n = 2,071) were recruited following breast-conserving surgery across eight centres in the UK, Europe and North America into the multicentre REQUITE cohort study (www.requite.eu) between 2014 and 2016.  Patient, treatment, and toxicity data (CTCAE v4.0) were collected prospectively.  QoL data (EORTC-QLQ-C30 and –B23) were available for 1,750 patients at baseline and on completion of radiotherapy.

Results

All patients have been genotyped using Illumina OncoArrays which assays ~600,000 SNPs including a GWAS backbone and a similar number of cancer-specific SNPs, of which 2,000 were selected from previous radiogenomics studies.  Results from the GWAS will be presented.  By the end of radiotherapy, 24.2 % of patients experienced ≥ grade 2 erythema, 31.6 % ≥ grade 1 oedema, and 9.5 % acute desquamation (skin or wound breakdown).  Overall, QoL (global health status), fatigue, pain, and breast symptoms worsened significantly by the end of radiotherapy (≥ 10 point change from baseline, dichotomised) compared to baseline (p<0.01). 

Conclusion

These GWAS results can be used to develop or improve clinical predictive risk models for toxicity and change in QoL from breast surgery and radiotherapy.  This has the potential to provide clinicians with important information when planning breast cancer treatment, in order to reduce side-effects and optimise quality of life.