Abstract 2614: Surgical weight loss via sleeve gastrectomy, but not a low-fat diet, reverses the pro-tumorigenic effects of obesity

Abstract

Abstract Background: Obesity is associated with increased incidence of basal-like breast cancer (BLBC), the most aggressive and lethal breast cancer subtype. Epidemiological data is conflicting regarding whether weight loss offers protection against BLBC in obese women; only interventions that typically result in significant sustained weight loss, such as bariatric surgery, produce a consistent anti-cancer benefit. Purpose: We sought to determine the differential effects of surgical and non-surgical weight loss interventions on inflammation, metabolic hormones and tumor burden in a mouse model of pre-menopausal breast cancer. Methods: Mice were fed a low fat control or high fat diet-induced obesity (DIO) regimen for 15 weeks to model chronic obesity. Diet-induced obese mice (n = 75) were randomized to receive either a surgical weight loss intervention (sleeve gastrectomy) or dietary weight loss intervention (switch to low fat control diet), resulting in formerly obese (FOb)-Surg or FOb-Diet mice, respectively. Additionally, a subset of mice remained on the DIO diet (Obese, n = 25), with another subset of normoweight control mice (Con, n = 25) maintained on a low fat diet throughout the study. FOb-Surg and FOb-Diet mice lost a nearly identical amount of weight and body fat; both groups had significantly lower weight and percent body fat than Con. Four weeks after weight stabilized, all mice on study were orthotopically injected with E0771 mammary tumor cells, which model BLBC. Results: At study endpoint, the average tumor weight in FOb-Surg mice was statistically equivalent to normoweight control mice. However, the average tumor weight in FOb-Diet mice was significantly greater than controls and statistically equivalent to the Obese mice. Furthermore, FOb-Surg mice had statistically lower levels of serum interleukin-6 and insulin compared to FOb-Diet, suggesting that in obese mice sleeve gastrectomy, relative to diet-induced weight loss, more effectively reduced obesity-associated inflammation, hyperinsulinemia and mammary tumor growth. Conclusion: Our results suggest that the strong anti-cancer benefits seen with bariatric surgery may be related to a significant reduction in systemic inflammation and growth factor signaling, which did not occur with non-surgical weight loss despite an equivalent amount of weight and body fat loss in FOb-Diet mice. Identifying the mechanisms underlying the protective effects of bariatric surgery against breast cancer could help identify new targets and strategies for breaking the obesity-cancer link. Citation Format: Emily L. Rossi, Laura W. Bowers, Subreen A. Khatib, Laura A. Smith, Steven S. Doerstling, Alfor Lewis, Randy J. Seeley, Stephen D. Hursting. Surgical weight loss via sleeve gastrectomy, but not a low-fat diet, reverses the pro-tumorigenic effects of obesity. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2614.