Abstract P5-12-07: Expression of adipocyte fatty acid binding protein promotes obesity-associated mammary tumor growth

Abstract

Abstract Background: The underlying mechanisms that drive obesity-related breast cancer remain unclear. Adipocyte/macrophage fatty acid binding protein (A-FABP) is linked to obesity and breast cancer, while transforming growth factor (TGF)β appears to play a pleiotropic role in breast cancer, suppressing its development but promoting its progression. Whether the proteins work together to drive breast cancer progression is not known. We evaluated the expression of these two markers in matched serum from healthy women and women with breast cancer. Hypothesis: A-FABP and TGFβ drive breast cancer development and progression. Methods: Serum was collected under an institutional review board approved protocol. A-FABP was measured in serum collected from 275 women (92 with breast cancer and 183 without) and TGFβ from 245 matched women (92 with breast cancer and 153 without). A-FABP levels were measured using a human A-FABP4 ELISA kit while TGFβ was measured using human TGFβ ELISA kit. The Kruskal-Wallis test was used to determine if a difference in marker expression existed between women with and without breast cancer, as well as in women with early vs. more advanced breast cancer. Linear mixed effect models were used to examine the relationship between A-FABP and BMI, as well as between TGFβ and BMI, controlling for age, menopause status and a diagnosis of breast cancer. Results:A-FABP expression was higher in obese than lean postmenopausal women, both those with breast cancer (mean : 44.9 vs. 25.1 ng/mL, p=0.002) and without breast cancer (39.4 vs. 26.9 ng/mL, p=0.003). A-FABP expression was also higher in premenopausal obese vs. lean women with cancer (28.9 vs. 12.7 ng/mL, p=0.027), but not in premenopausal healthy women. A-FABP expression was higher in postmenopausal obese vs. lean women with early stage (0-2A) breast cancer (45.6 vs. 21.9 ng/mL, p=0.013) and was inversely associated with HER-2 expression, though being of borderline significance (p=0.060). This was most notable among triple negative vs. ER/PR negative HER2 positive breast cancers. Considering both early and advanced breast cancer, TGFβ expression trended higher in post- than in pre-menopausal obese women with breast cancer (138.9 vs. 68.7 pg/mL, p=0.061), however among premenopausal women with advanced (Stages 2B-3C) disease, TGFβ expression was 5 fold higher in lean than obese individuals (251.7 vs. 48.2 pg/mL, p=0.029) but trended higher in obese vs lean postmenopausal women. TGFβ and A-FABP were found to be significantly associated (ρ=0.14, p=0.024). Impact: Both A-FABP and TGFβ expression are associated with postmenopausal breast cancer among obese women, and their expression in matched samples is significantly associated.. TGFβ is associated with premenopausal advanced breast cancer in premenopausal women. TGFβ is known to induce epithelial mesenchymal transition and may play a role in pregnancy associated breast cancer. Further studies are needed to determine if A-FABP and TGFβ work together in postmenopausal breast cancer. Citation Format: Sauter E, Hao J, Yan X, Kong M, Li B. Expression of adipocyte fatty acid binding protein promotes obesity-associated mammary tumor growth [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-12-07.