Molecular profile of tumor-associated adipose in obese women with breast cancer

Breast tumors have a direct physical and vascular interface with white adipose tissue, making them ideal model systems to study the adipose-tumor microenvironment, especially within the context of obesity. As a first initiative to understanding how adipose tissue contributes to breast tumor etiology, we explored cancer-associated adipose tissue in patients with invasive breast cancer. We hypothesized that obesity leads to greater alterations in cancer-associated adipose tissue by expressing genes involved in cellular growth, angiogenesis, and invasion, thus providing support for breast cancer progression. We also proposed that adipocytes adjacent to tumors express a genotype unique to obese breast cancers. Adipose tissue samples (n=10) were obtained from obese and lean women with breast cancer. Within individuals, tissue was sampled proximal and distal (2 cm) to the tumor. Using next-generation whole transcriptome sequencing, we examined genes from cancer-associated adipose tissue in both groups. A heat map of normalized expression values was generated with unsupervised clustering and the fifty most informative genes. Samples from obese individuals with breast cancer tended to cluster together. There were significant gene differences between adipose collected proximal versus distal from the tumor in obese but not in lean women, such as genes associated with myosin heavy chains MYH1, 4, 8, and 11 (adj. p < 0.05). In examining obese women, there were 16 Hallmark pathways that were statistically significant (adj. p < 0.10); whereas a subset of these (11 pathways) were significant in lean women. Of interest, pathways that were significant in both were pathways that regulate EMT, adipogenesis and TGF beta signaling. The molecular signature of cancer-associated adipocytes is different between lean and obese patients. (Supported by NIH P20GM103434 and NIGMS U54GM104942) Citation Format: Niel Infante, James Coad, Donald Primerano, James Denvir, Linda Vona-Davis. Molecular profile of tumor-associated adipose in obese women with breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4241.