Precision Medicine in Breast Cancer (B-PRECISE): Managing residual disease and drug resistance in breast cancer

Residual disease after therapy and emergence of drug resistance remain key challenges in breast cancer management. B-Precise is addressing these questions through the development of multimodal genomic, imaging and pathology based tools, developed from retrospective and prospective clinical cohorts of breast cancer patients. Our goal is to develop sensitive whole genome assays for residual circulating tumour DNA in plasma and other fluids and combine these with digital imaging and digital pathology, to identify patients at high risk of early relapse. The benefits of identifying high risk of relapse will be tested through prospective clinical studies/entry to clinical trials. Our initial focus will be on developing this approach with TNBC patients post neo-adjuvant treatment where early data point to a potential benefit of ctDNA assays in identifying residual disease.Similar questions pertain to resistance in ER+ disease and HER2+ high risk patients and these subgroups will be incorporated in prospective cohorts with the same technologies. Additionally, recent work has identified novel structural and SNV genome instability patterns as an important genomic stratification that may assist in prediction of platinum and PARP resistance. Through intensive genomic sequencing and multimodal data integration on established and future prospective cohorts of TNBC patients, relationships between genomic instability, tissue immune cell interfaces and treatment responses to standard agents will be addressed. 

Precision Medicine for Breast Cancer (B-PRECISE) research is a provincial scope multi-investigator network of clinicians and scientists across each of the six BC Cancer centers. B-PRECISE aims to better understand how tumors evolve, how to treat them most effectively, how to prevent cancer from returning and how to identify patients at high-risk who may require more intensive therapies. Our project will identify patterns of drug resistance and sensitivity in patients that continue to have residual disease and sensitivity after they complete treatment through multimodal, genomics based understanding of breast cancer heterogeneity. Our approach will be done through two sub projects. Sub project (1) Minimal residual disease management in ER+ and HER2+ breast cancer patients and sub project (2) Targeting drug resistance in triple negative breast cancers (TNBC).