Title: EARLY BREAST CANCER META-ANALYSES AND TRIALS Early Breast Cancer Trialists' Collaborative Group (EBCTCG), and AgeX NHS breast screening trial
Funder: Cancer Research UK

Abstract: Background The EBCTCG undertake meta-analyses of individual patient data from randomised trials worldwide that compare the effects of different surgery, radiotherapy, endocrine and chemotherapy, biological, and other treatments on breast cancer recurrence, serious toxicity, and long-term cause-specific mortality. The 22 EBCTCG meta-analysis publications have identified many moderate improvements in treatment that were not apparent from individual trials, influencing worldwide treatment patterns, which has been a major contributor to a halving of breast cancer death rates in the UK and elsewhere. When important questions remain unresolved, the EBCTCG secretariat have initiated and coordinate ‘mega-trials’ such as ATLAS and aTTom that demonstrated the benefit of extending tamoxifen treatment to 10 years, and the ongoing AgeX breast cancer screening trial. EBCTCG meta-analyses are laborious requiring extensive literature searching, communication with trialists, careful checking and querying of each individual study, extensive analyses, discussions with trialists, agreement of reports, and publication. Funding is needed to allow the EBCTCG secretariat’s team of specialists in systematic review, statistics, oncology, surgery, and information technology to continue this work. Aims To identify successive improvements in early breast cancer detection and treatment, to investigate whether benefits vary by type of tumour, to influence international treatment guidelines and thereby reduce breast cancer mortality worldwide. Methods Early diagnosis: Meta-analysis of mammographic breast screening trials. AgeX, embedded in the NHS breast screening programme, will randomise a further 3 million women to receive or not mammographic screening outside the current 50-70 age range. Treatment: EBCTCG will undertake numerous new meta-analyses of chemotherapy (eg taxanes±anthracyclines), endocrine therapy (eg extending aromatase inhibitor treatment beyond 5 years), biological therapy (addition of trastuzumab, longer vs shorter trastuzumab, trastuzumab vs other HER2-directed therapies), local therapy (partial breast/tumour bed boost radiotherapy, regional nodal radiotherapy, axillary treatment after sentinel node biopsy), and will update previous meta-analyses that remain of contemporary relevance. Individualising treatments: Studies of stored tissue from randomised trials will be identified, data centrally collated and analysed to identify tumour characteristics such as Ki-67 that might influence the response to adjuvant therapies. The relationship of these and patient characteristics (eg body mass index) to prognosis will be assessed. How these results will be used Rigorous evaluation of the benefits and risks of different treatments and of screening mammography, and the clinical relevance of different tumour characteristics, will greatly facilitate treatment decisions for individual women with early breast cancer and their doctors.

Lay abstract: Background The EBCTCG undertake meta-analyses of individual patient data from randomised trials worldwide that compare the effects of different surgery, radiotherapy, endocrine and chemotherapy, biological, and other treatments on breast cancer recurrence, serious toxicity, and long-term cause-specific mortality. The 22 EBCTCG meta-analysis publications have identified many moderate improvements in treatment that were not apparent from individual trials, influencing worldwide treatment patterns, which has been a major contributor to a halving of breast cancer death rates in the UK and elsewhere. When important questions remain unresolved, the EBCTCG secretariat have initiated and coordinate ‘mega-trials’ such as ATLAS and aTTom that demonstrated the benefit of extending tamoxifen treatment to 10 years, and the ongoing AgeX breast cancer screening trial. EBCTCG meta-analyses are laborious requiring extensive literature searching, communication with trialists, careful checking and querying of each individual study, extensive analyses, discussions with trialists, agreement of reports, and publication. Funding is needed to allow the EBCTCG secretariat’s team of specialists in systematic review, statistics, oncology, surgery, and information technology to continue this work. Aims To identify successive improvements in early breast cancer detection and treatment, to investigate whether benefits vary by type of tumour, to influence international treatment guidelines and thereby reduce breast cancer mortality worldwide. Methods Early diagnosis: Meta-analysis of mammographic breast screening trials. AgeX, embedded in the NHS breast screening programme, will randomise a further 3 million women to receive or not mammographic screening outside the current 50-70 age range. Treatment: EBCTCG will undertake numerous new meta-analyses of chemotherapy (eg taxanes±anthracyclines), endocrine therapy (eg extending aromatase inhibitor treatment beyond 5 years), biological therapy (addition of trastuzumab, longer vs shorter trastuzumab, trastuzumab vs other HER2-directed therapies), local therapy (partial breast/tumour bed boost radiotherapy, regional nodal radiotherapy, axillary treatment after sentinel node biopsy), and will update previous meta-analyses that remain of contemporary relevance. Individualising treatments: Studies of stored tissue from randomised trials will be identified, data centrally collated and analysed to identify tumour characteristics such as Ki-67 that might influence the response to adjuvant therapies. The relationship of these and patient characteristics (eg body mass index) to prognosis will be assessed. How these results will be used Rigorous evaluation of the benefits and risks of different treatments and of screening mammography, and the clinical relevance of different tumour characteristics, will greatly facilitate treatment decisions for individual women with early breast cancer and their doctors.

Research activity codes: 4.4 POPULATION SCREENING;6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION)
Health categories: CANCER AND NEOPLASMS