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
Session type: Poster / e-Poster / Silent Theatre session
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.
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.
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).
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.