Scientific Rationale:Thanks to therapeutic advances, breast cancer survival rates have significantly improved, but cardiovascular disease (CVD) has become a leading cause of morbidity and mortality among survivors, with risks comparable to cancer recurrence. Key treatments such as anthracyclines, targeted therapies, and radiotherapy all carry cardiotoxic risks. However, our understanding of the true incidence of various CVD subtypes, effective early predictive biomarkers, and genetic susceptibility remains limited. The UK Biobank, with its prospective cohort of over 500,000 individuals, long-term follow-up records, and deep multimodal data (cardiac imaging, proteomics, genomics), offers a unique platform to systematically address these critical questions in cardio-oncology.
Research Questions & Objectives:
This study aims to leverage the UK Biobank’s multimodal data to comprehensively characterize the determinants of cancer therapy-related cardiac dysfunction (CTRCD).
Core Questions:
1) What is the long-term cardiovascular risk for breast cancer survivors?
2) Can new imaging and proteomic biomarkers be identified for early prediction?
3) Is there a genetic predisposition to cardiotoxicity?
Specific Objectives:
Quantify Risk: To precisely calculate and compare the incidence rates of various CVDs (e.g., heart failure, myocardial infarction) between breast cancer survivors and matched controls, and to assess the synergistic effect of a cancer diagnosis with baseline risk factors.
Discover Biomarkers: To integrate cardiac magnetic resonance (CMR) imaging phenotypes and circulating protein profiles to identify novel, non-invasive biomarkers that predict subclinical cardiac injury and long-term CVD risk.
Elucidate Genetic Mechanisms: To identify genetic variants associated with CTRCD through genome-wide association studies (GWAS) and to develop a polygenic risk score (PRS) for more accurate, individualized risk stratification.
