Abstract 4216: Adiponectin, leptin and breast cancer in high risk postmenopausal women: Results from a nested case-control study

Abstract

Abstract Introduction: Obesity is a risk factor for postmenopausal breast cancer (BC) and evidence supports the pivotal role of adipokines in the association between obesity and BC. In the present study, we aim to investigate the role of adiponectin and leptin as independent risk markers for postmenopausal BC in a prospective nested case-control study within the cohort of women from the International Breast cancer Intervention prevention Study II (IBIS-II). Methods and Results: In the IBIS-II Prevention trial, 3864 healthy postmenopausal women at increased risk for BC were randomized to receive 1 mg/day oral anastrozole or matching placebo for 5 years. We measured serum adiponectin and leptin at baseline and 12-months in 119 cases and 336 controls in the placebo arm, and 57 cases and 165 controls in the anastrozole arm. We performed the adipokines measurements on the automated immunoassay platform ELLA (ProteinSimple, Biotechne). Baseline characteristics (age, body mass index (BMI), smoking status, and oophorectomy) were not different between cases and controls in both trial arms, except for hormone replacement therapy (HRT) use (38.7% of cases vs 51.5% of controls) and hysterectomy (25.2% of cases vs 37.5% of controls) in the placebo arm. We did not observe any statistically significant difference in adiponectin and leptin at baseline between cases and controls in both trial arms. When we considered the change in adiponectin levels between baseline and 12-months of follow-up, we observed a borderline significant higher proportion of BC cases in subjects with a decrease in adiponectin (36.4%) compared to subjects with an increase in adiponectin (25.7%). The multivariate Cox model indicated that women on placebo with a decrease in adiponectin between baseline and 12-months had a 36% significant increased risk in BC (HR=0.64; CI 0.42-0.98; adjusted for age, BMI, previous HRT use, smoking, oophorectomy, hysterectomy). Changes in leptin were not significantly associated with BC incidence overall. However, the multivariate Cox model for the anastrozole arm, indicated a significant higher BC risk for women with the highest increase (>10 ng/ml) vs the lowest decrease (<-10 ng/ml) in leptin: HR=4.45; CI 1.08-18.30; adjusted for age, BMI, previous HRT use, smoking, oophorectomy, hysterectomy. Conclusion: Our results did not support a prognostic role of baseline adiponectin and leptin levels in postmenopausal BC development. However, we observed an increased BC risk in women with a 12-month adiponectin decrease and leptin increase. These data suggest further investigations of changes of adiponectin and leptin levels as attractive targets for BC prevention in postmenopausal women at high risk for BC. Citation Format: Debora Macis, Ivana Sestak, Valentina Aristarco, Harriet Johansson, Aliana Guerrieri-Gonzaga, Andrea Decensi, Bernardo Bonanni, Jack Cuzick, Sara Gandini. Adiponectin, leptin and breast cancer in high risk postmenopausal women: Results from a nested case-control study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4216.