A Mediation Analysis of Obesity and Adiponectin Association with Postmenopausal Breast Cancer Risk: A Nested Cohort Study in the International Breast Cancer Intervention Study II (IBIS-II) Prevention Trial
Debora Macis,
Federica Bellerba,
Valentina Aristarco,
Harriet Johansson,
Aliana Guerrieri-Gonzaga,
Matteo Lazzeroni,
Ivana Sestak,
Jack Cuzick,
Andrea DeCensi,
Bernardo Bonanni,
Sara Gandini
Affiliations
Debora Macis
Division of Cancer Prevention and Genetics, European Institute of Oncology (IEO), Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), 20141 Milan, Italy
Federica Bellerba
Molecular and Pharmaco-Epidemiology Unit, Department of Experimental Oncology, European Institute of Oncology (IEO), Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), 20139 Milan, Italy
Valentina Aristarco
Division of Cancer Prevention and Genetics, European Institute of Oncology (IEO), Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), 20141 Milan, Italy
Harriet Johansson
Division of Cancer Prevention and Genetics, European Institute of Oncology (IEO), Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), 20141 Milan, Italy
Aliana Guerrieri-Gonzaga
Division of Cancer Prevention and Genetics, European Institute of Oncology (IEO), Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), 20141 Milan, Italy
Matteo Lazzeroni
Division of Cancer Prevention and Genetics, European Institute of Oncology (IEO), Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), 20141 Milan, Italy
Ivana Sestak
Wolfson Institute of Population Health, Queen Mary University of London, London EC1M 6BQ, UK
Jack Cuzick
Wolfson Institute of Population Health, Queen Mary University of London, London EC1M 6BQ, UK
Andrea DeCensi
Wolfson Institute of Population Health, Queen Mary University of London, London EC1M 6BQ, UK
Bernardo Bonanni
Division of Cancer Prevention and Genetics, European Institute of Oncology (IEO), Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), 20141 Milan, Italy
Sara Gandini
Molecular and Pharmaco-Epidemiology Unit, Department of Experimental Oncology, European Institute of Oncology (IEO), Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), 20139 Milan, Italy
Obesity is a risk factor for postmenopausal breast cancer (BC), and evidence suggests a role for adiponectin in the relationship between obesity and BC. We investigated whether adiponectin or other biomarkers mediate the effect of body mass index (BMI) on postmenopausal BC risk in a cohort study nested in the IBIS-II Prevention Trial. We measured adiponectin, leptin, IGF-I, IGFBP-1, high-sensitivity C-reactive protein, glycemia, insulin, HOMA-IR index, and SHBG in baseline and 12-month serum samples from 123 cases and 302 matched controls in the placebo arm of the IBIS-II Prevention trial. We conducted the main mediation analysis considering baseline BMI as an exposure and the 12-month adiponectin increase as a mediator after adjustment for the Tyrer–Cuzick score and the lipid-lowering medications/supplements use. In the multivariable Cox model, both the 12-month adiponectin increase (HR, 0.60; 95%CI, 0.36–1.00) and BMI were associated with BC risk (HR, 1.05; 95%CI, 1.00–1.09), with a 40% reduction in women with a 12-month increase in adiponectin. A significantly higher cumulative hazard of BC events was observed in obese women (BMI > 30) with decreased adiponectin (p = 0.0087). No mediating effect of the adiponectin increase on the total effect of BMI on BC risk was observed (natural indirect effect: HR, 1.00; 95%CI, 0.98–1.02). Raising adiponectin levels might be an attractive target for postmenopausal BC prevention.