Abstract P4-11-16: Low serum adiponectin level is an independent risk factor of DCIS in postmenopausal women at increased risk of breast cancer

Background:The assessment of breast cancer (BC) risk is a key step for an effective preventive treatment. Besides the established risk assessment models, validation of independent predictive factors such as circulating biomarkers would improve patient selection and treatment efficacy. Obesity and metabolic imbalance play an important role in BC risk in menopausal women. The role of adipocytes in energy homeostasis is currently under investigation for their emerging relationship with BC. Adipokines (such as leptin and adiponectin) are linked to insulin sensitivity and have been related to BC risk and prognosis. Adiponectin, a peptide hormone secreted by the adipose tissue, has been inversely related to BC risk both in observational studies and in a phase II chemoprevention trial in premenopausal women at increased risk. Aim:We measured baseline serum adiponectin and leptin levels as well as HOMA index, in 534 postmenopausal women enrolled in 16 Italian centers and randomized in one of the two international phase III trials for BC prevention -the IBIS-II(Prevention) and IBIS-II(DCIS) trials- to assess whether these biomarkers were different in the healthy women at increased risk for BC cohort compared to the DCIS cohort. Methods:Healthy postmenopausal women (aged 40-70) at increased risk for BC (on an age-dependent risk model; n=186) or DCIS patients who underwent radical surgery in the previous 6 months (n=348) were eligible according to the two separate protocol entry criteria. At baseline, fasting blood was collected, processed and stored at -80°C till biomarkers measurement. Insulin and glucose levels were measured with the Architect system (Abbott Laboratories, Abbott Park, IL 60064 USA). Serum adiponectin and leptin levels were determined with Immunoassays by R&D (Minneapolis, USA). Results:Participant characteristics and biomarker levels (median, IQ range) by disease status are reported below. Table 1Healthy (n=186)DCIS (n=348)Age at entry59 (55, 63)60 (56, 65)BMI (kg/m2)25.2 (22.9, 28.4)25.0 (22.4, 28.1)Adiponectin (ng/mL)13063 (10279, 18157)11498 (7722, 16909)Leptin (pg/mL)16181 (9594, 26391)17284 (9675, 26173)L/A ratio1.33 (0.60, 2.09)1.46 (0.69, 3.19)Glucose (mg/dL)89 (81, 97)93 (86, 103)Insulin (μU/mL)6.6 (5.0, 9.6)7.5 (5.4, 10.6)HOMA index1.39 (1.04, 2.02)1.79 (1.18, 2.61)L/A, Leptin/Adiponectin ratio Adiponectin was significantly negatively correlated with leptin, L/A ratio, HOMA index and BMI, while leptin was positively correlated with L-A ratio, BMI, HOMA. Logistic regression has been used and Odds Ratios (ORs) have been calculated to assess the association of DCIS with biomarkers.DCIS patients were significantly more frequent in the lowest quartile of adiponectin compared to the highest quartile (60% vs 75%; OR=2.49; 95% CI, 1.39-4.44, p= 0.0003) adjusting for center, BMI, HOMA index and age. Conclusions:Low serum adiponectin levels in postmenopausal women are more frequent in DCIS patients compared to healthy at risk subjects independently of BMI, HOMA index and age and results are similar to premenopausal women. Future investigations in both trials will assess whether adiponectin is also associated with BC events. Acknowledgments: J.Forbes and T.Howell, Co-Chairmen,IBIS-II Steering Committee. Citation Format: Aliana Guerrieri-Gonzaga, Debora Macis, Sara Gandini, Valentina Aristarco, Harriet Johansson, Giorgia Bollani, Teresa Roth, Maria-Teresa Sandri, Jill Knox, Jack Cuzick, Bernardo Bonanni. Low serum adiponectin level is an independent risk factor of DCIS in postmenopausal women at increased risk of breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-11-16.