Central and peripheral adiposity and breast cancer risk in postmenopausal women: A pooled analysis of 11 cohort studies

Background: Central and peripheral adiposity, measured by waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR), has been positively associated with postmenopausal breast cancer (BC) risk, but results are inconsistent after adjustment for body mass index (BMI). Using pooled individual-level data from 11 prospective cohorts, we evaluated associations between WC, HC, WHR, and a body shape index (ABSI; based on waist, height, and weight) and risk of postmenopausal BC overall and BC subtypes defined by receptor status. Methods: These preliminary analyses evaluated associations between WC, HC, WHR, and ABSI using consortium-wide quintiles and overall BC and tumor negative breast cancer (TNBC) in 402,682 postmenopausal women. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CI), adjusting for age, year of questionnaire, study, family history of BC, and reproductive and lifestyle factors. Analyses were performed with and without adjustment for BMI. Results: During a median follow-up of 2.9-27.5 years across studies, 20,752 incident invasive BC were documented (N=998 TNBC). The pooled multivariable BMI-adjusted HRs (95% CIs) for postmenopausal BC comparing quintile 5 to 2 were 1.14 (1.08-1.21) for WC; 1.06 (0.99-1.14) for HC; 1.10 (1.05-1.15) for WHR, and 1.03 (0.98-1.08) for ABSI. Similar associations were observed among never-users of menopausal hormone therapy. The pooled multivariable BMI-adjusted HRs (95% CIs) for postmenopausal TNBC comparing quintile 5 to 2 were 1.13 (0.87-1.46) for WC; 0.74 (0.45-1.21) for HC; 1.45 (1.15-1.84) for WHR, and 1.18 (0.95-1.47) for ABSI. Conclusion: Higher compared to lower WC and WHR were associated with increased risk of postmenopausal BC, independent of BMI. Our findings suggest that individual and population-level strategies to prevent central adiposity could help reduce the risk of postmenopausal BC. Pooled Multivariable (MV) Hazard Ratios (HR) and 95% Confidence Intervals (CI) Consortium-wide quintiles Overall TNBC WC (cm) <74 0.97 (0.92-1.02) 0.92 (0.74-1.15) 74-<80 REF REF 80-<86 1.0 (0.95-1.04) 0.89 (0.73-1.1) 86-<95 1.06 (1.02-1.12) 0.94 (0.76-1.17) ≥95 1.14 (1.08-1.21) 1.13 (0.87-1.46) HC (cm) <95 0.91 (0.87-0.96) 0.91 (0.60-1.36) 95-<100 REF REF 100-<105 1.03 (0.98-1.08) 1.15 (0.82-1.65) 105-<112 1.03 (0.98-1.09) 0.92 (0.60-1.4) ≥112 1.06 (0.99-1.14) 0.74 (0.45-1.21) WHR <75 1.02 (0.97-1.07) 1.37 (1.1-1.69) 75-<79 REF REF 79-<83 1.04 (1.0-1.09) 1.27 (1.01-1.59) 83-<87 1.03 (0.98-1.08) 1.29 (1.02-1.62) ≥87 1.1 (1.05-1.15) 1.45 (1.15-1.84) ABSI <71 0.97 (0.93-1.01) 1.09 (0.91-1.32) 71-74 REF REF 74-77 1.01 (0.97-1.05) 1.09 (0.89-1.33) 77-81 1.02 (0.98-1.07) 1.17 (0.95-1.43) ≥81 1.03 (0.98-1.08) 1.18 (0.95-1.47)