Use of real world data to generate evidence on the effectiveness of oncological treatment provision in older/underrepresented populations of women diagnosed with breast cancer

Background: Evidence on oncological treatment efficacy from randomised controlled trials (RCTs) forms the backbone to national guidance on clinical practice but their findings may have limited generalisability. This is a particular concern when applying guidance about treatments to older patient populations who can be poorly represented within RCTs. This thesis examined the value of routinely-collected data sources in evaluating oncological treatments for patients with invasive breast cancer (IBC). Methods: Cancer Registration records for women aged 50+ years newly-diagnosed with IBC in England from 2014-2019 were used, linked at patient/tumour-level to routine national datasets providing information on patient and tumour characteristics, treatment and survival outcomes. Initial work examined methodological challenges in understanding oncological treatments using routine data sources. Work then investigated clinical aspects of oncological treatments received in practice, focusing on their uptake, and the safety and benefit of trastuzumab-based treatment for HER2-positive early invasive breast cancer (EIBC) among older, less fit patients. Results: There were systematic differences in oncological treatment recording within available national data sources, with records less complete for older patients. For endocrine therapy, completeness was excellent in primary care data but linkage to secondary care data identified initial hospital-based prescriptions, providing more comprehensive information about treatment timings. Use of oncological treatments was consistently lowest among older women, independent of other relevant factors. Trastuzumab-based treatment for HER2-positive EIBC had comparable overall safety among both younger and older women, although increasing age was associated with increased odds of cardiovascular problems. There was no evidence of differences in the effect of trastuzumab on survival by age. Conclusions: This research has demonstrated the value of routine national data in understanding treatment use and associated outcomes among patients with IBC treated in routine care. Similar studies may address evidence gaps in other treatment areas where patient representation in RCTs is an issue.