E Harvey-Jones, M Raghunandan, L Robbez-Masson, L Magraner-Pardo, T Alaguthurai, A Yablonovitch, J Yen, H Xiao, R Brough, J Frankum, F Song, J Yeung, T Savy, A Gulati, J Alexander, H Kemp, C Starling, A Konde, R Marlow, M Cheang, P Proszek, M Hubank, M Cai, J Trendell, R Lu, R Liccardo, N Ravindran, A Llop-Guevara, O Rodriguez, J Balmana, N Lukashchuk, M Dorschner, L Drusbosky, I Roxanis, V Serra, S Haider, S J Pettitt, C J Lord, A N J Tutt
BACKGROUND: Resistance to therapies that target homologous recombination deficiency (HRD) in breast cancer limits their overall effectiveness. Multiple, preclinically validated, mechanisms of resistance have been proposed, but their existence and relative frequency in clinical disease are unclear, as is how to target resistance. PATIENTS AND METHODS: Longitudinal mutation and methylation profiling of circulating tumour (ct)DNA was carried out in 47 patients with metastatic BRCA1-, BRCA2- or PALB2-mutant breast cancer treated with HRD-targeted therapy who developed progressive disease-18 patients had primary resistance and 29 exhibited response followed by resistance...
January 19, 2024: Annals of Oncology: Official Journal of the European Society for Medical Oncology