Abstract GS2-09: Overweight, Obesity and Prognosis in 206,904 Women in the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) Database

Background: Analyses of the 2014 EBCTCG database suggested that, in early-stage breast cancer, obesity was strongly independently associated with breast cancer mortality only in pre/peri-menopausal oestrogen-receptor-positive (ER+) disease (Pan et al ASCO 2014). Based on the far larger 2024 EBCTCG database, however, we can now test that unexpected finding and better characterise any relevance of patient characteristics to the association of body mass index (BMI) with distant recurrence and mortality. Methods: We analysed patient-level data on time to distant recurrence and death from the 206,904 women with early-stage breast cancer (entered during 1978-2017 into 147 randomised trials) in the 2024 EBCTCG database who had BMI at entry (within two years of diagnosis) recorded as 15-50 kg/m2 and with complete information on age, ER status, tumour diameter, nodal status, and randomly allocated treatment. Information on menopausal status, tumour grade, and HER2 status was available for most participants. Cox regression was used to estimate the associations of BMI with rates of distant recurrence and breast cancer mortality, calculating hazard rate ratios (RRs) per 5 kg/m2 increase of BMI or comparing 3 BMI groups (obese: BMI 30-50 [mean 34.7]; overweight: BMI 25 to <30 [mean 27.3]; lean: BMI 15 to <25 [mean 22.2] kg/m2). Results: Of the 206,904 women, 60% were postmenopausal at trial entry and 77% had ER+ disease. Their mean BMI was 27.1 (SD 5.6) kg/m2 and 26.0% (53,872) were obese (BMI ≥30 kg/m2). The prevalence of obesity increased from 19% in the early 1980s to 27% in the early 2010s. The overall adjusted rate ratio (RR) of first distant recurrence (ignoring any local or contralateral recurrences) was 1.06 (95% CI 1.05-1.07, p<0.0001) per 5 kg/m2 increase in BMI. The RR for overweight versus lean women was 1.07 (CI 1.04-1.10, p<0.0001), and that for obese versus lean women was 1.17 (95% CI 1.14-1.20, p<0.0001). This approximately log-linear association between BMI and the rate of distant recurrence was seen irrespective of patient or tumour characteristics, type of adjuvant systemic therapy, year of diagnosis, or time since diagnosis. In the 82,464 pre-menopausal women the RR per 5 kg/m2 increase of BMI was 1.08 (1.07-1.10, p<0.0001), and in the 124,440 post-menopausal women it was 1.05 (1.03-1.06, p<0.0001; heterogeneity between RRs p=0.0004). There was little heterogeneity between the RRs in ER+ and ER-poor disease. In the 159,119 women with ER+ disease the RR per 5 kg/m2 increase of BMI was 1.06 (1.05-1.08, p<0.0001), and in the 47,785 with ER-poor disease it was 1.06 (1.04-1.08, p<0.0001). The associations of BMI with breast cancer mortality mirrored those with distant recurrence. Conclusion: Overweight and obesity are associated with increased distant recurrence and breast cancer mortality in all types of patients with early-stage breast cancer, but the risk associated with a substantial (e.g. 5 kg/m2) difference in BMI is only moderate. Nevertheless, randomised assessment of the effects among overweight or obese women with early breast cancer of weight-loss interventions (perhaps utilising a GLP-1 receptor agonist) could usefully be added, using a factorial design, to some current and future adjuvant treatment trials addressing unrelated questions. Reference: Pan H, Gray R, on behalf of the EBCTCG. Effect of obesity in premenopausal ER+ early breast cancer: EBCTCG data on 80,000 patients in 70 trials. J Clin Oncol 2014; 32:5s Citation Format: Hongchao Pan, Richard Gray, Richard Peto, Jeremy Braybrooke, David Dodwell, Robert Hills, Rosie Bradley, Hellen Gelband, Hui Liu, Paul McGale, Carolyn Taylor, Mike Clarke, Wolfgang Janni, Marianne Ewertz, Pamela J Goodwin, Joseph Sparano, Kathy I Pritchard, Jonas Bergh, Sandra M Swain, for the Early Breast Cancer Trialists™ Collaborative Group (EBCTCG). Overweight, obesity and prognosis in 206,904 women in the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) database [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr GS2-09.