Abstract P4-04-28: Weight loss reversed the carcinogenic effect of obesity on basal-like breast cancer

Abstract

Abstract Epidemiologic studies demonstrate that obesity is associated with a subtype of breast cancer called basal-like breast cancer (BBC), which is fast proliferating and aggressive, with no targeted therapies. Using the C3(1)-TAg murine model of BBC, we have previously shown that obese adult mice displayed significantly decreased tumor latency compared to lean mice with induction of the oncogenic HGF/c-Met pathway. Reducing adiposity is predicted to lower incidence of BBC in human population studies. Thus, the objective of this study was to investigate how a diet-switch to reduce obesity affected BBC onset and early progression. C3(1)-TAg mice were placed on a control low fat diet (LFD) and remained lean, high-fat diet (HFD) to induce obesity, and a group made obese by HFD that were then switched to LFD to induce weight loss. Just two weeks after weight loss, mice in the diet switch group had weights and adiposity similar to lean mice. Weight loss caused a 51.4% decrease in adiposity (P<0.0001) compared to obese mice. Importantly, mice that lost weight displayed significantly delayed tumor latency (17 week) compared to obese mice on HFD (15 week), with no differences detected in tumor burden or growth. Therefore the obese microenvironment that promotes early tumor onset can be reprogrammed with weight loss and restoration of a lean phenotype. Ongoing studies are examining HGF/cMet expression by immunohistochemistry in normal mammary glands and tumors to determine the contribution of this obesity-responsive pathway. Metabolomics and RNAseq analysis will identify novel obesity-dependent pathways relevant to BBC. In conclusion, we demonstrated that loss of adiposity protected against early BBC onset. Further research will identify important biomarkers associated with obesity and weight loss that can be compared through conserved biology approaches. Citation Format: Yuanyuan Qin, Sneha Sundaram, Liyang Zhao, Luma Essaid, Kirk K McNaughton, Katharine M Bendt, David B Darr, Melissa A Troester, Liza Makowski. Weight loss reversed the carcinogenic effect of obesity on basal-like 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 P4-04-28.