Abstract P5-06-03: Effect of obesity on molecular characteristics of invasive breast tumors: Gene expression analysis of 405 tumors by BMI

Abstract

Abstract Background: Obesity is a risk factor for breast cancer in postmenopausal women and weight gain after diagnosis is associated with decreased survival and less favorable clinical characteristics such as greater tumor burden, higher grade, and poor prognosis, regardless of menopausal status. Despite the negative impact of obesity on clinical outcome, the molecular mechanisms by which excess adiposity influences breast cancer are not well-understood. Methods: Affymetrix U133 2.0 gene expression data was available for 405 primary breast tumors and 20 tumor-adjacent adipose tissues; RNA was isolated from tumor epithelia or adipose using laser microdissection. Patients were classified as lean (BMI<25), overweight (BMI 25-29.9) or obese (BMI>30). Statistical analysis was performed by ANOVA using Partek Genomics Suite version 6.6. Results: Obese patients were significantly more likely to be diagnosed >50 years and to be of African American ancestry compared to lean or overweight women, while pathological characteristics including tumor stage, size or grade, lymph node status and intrinsic subtype did not differ significantly between groups. Principal component analysis could not effectively cluster the tumors by weight and no genes were differentially expressed using a false discovery rate <0.05. Using a less stringent unadjusted P-value of <0.01, 329 genes were differentially expressed, however, this gene expression profile could not discriminate patient tumors by BMI. In contrast, BMI was effective in clustering tumor-adjacent adipose samples by BMI based on differential expression of 156 genes. Conclusions: Although tumor epithelial cells from obese women do not differ significantly from those of lean and/or overweight women at the gene expression level, tumor-adjacent adipose did differ by weight. These data demonstrate that less favorable outcomes in obese patients are not be attributable to the tumor itself but to influences from the microenvironment and suggest that decreasing breast adiposity may be an effective strategy to reducing risk and improving outcomes in obese women. Citation Format: Ellsworth RE, Toro AL, Costantino NS, Shriver CD, Ellsworth DL. Effect of obesity on molecular characteristics of invasive breast tumors: Gene expression analysis of 405 tumors by BMI. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-06-03.