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Bariatric surgery and breast cancer

Bariatric surgery beats diet at inhibiting breast cancer

(Credit: Bakerstmd)
Tumour growth in obese mice that had bariatric surgery was statistically equivalent to mice that had maintained a normal weight

Bariatric surgery was more effective than a low-fat diet at reversing the cancer-promoting effects of chronic obesity in mice, according to a study by UNC Lineberger Comprehensive Cancer Center researchers, who presented ‘Surgical weight loss via sleeve gastrectomy, but not a low-fat diet, reverses the pro-tumorigenic effects of obesity’, at the 2016 American Association of Cancer Research Annual Meeting in New Orleans.

"Our basic finding was that surgical weight loss in obese mice was able to inhibit mammary tumor growth in a mouse model of basal-like breast cancer, while weight loss induced by a low fat, low calorie diet was not," said Dr Emily Rossi, the paper's first author and a pre-doctoral trainee with the UNC Lineberger Cancer Control and Education Program.

Rossi and her colleagues in the lab of Dr Stephen Hursting, a UNC Lineberger member and professor of nutrition in the UNC Gillings School of Global Public Health and the UNC Nutrition Research Institute, are leading research to understand and potentially break the link between obesity and cancer.

"Data from human studies has suggested that there is something mechanistically different about bariatric surgery, relative to diet-induced weight loss, that makes the surgery more effective at preventing or controlling breast cancer," said Hursting. "Now that we have (for the first time) replicated this surgery versus diet effect in an experimental model of breast cancer, we have the opportunity to determine the molecular and metabolic factors that are responsible for the protective effects of the surgery."

Obesity is a significant risk factor for several types of breast cancer, including basal-like breast cancer (BLBC)  subtype. Rossi, Hursting and their colleagues have shown in previous research that obesity reversal through diet may not be enough to reverse the effects of chronic obesity on molecular drivers of cancer, including epigenetics and inflammation.

Therefore, they sought to determine the differential effects of surgical and non-surgical weight loss interventions on inflammation, metabolic hormones and tumour burden in a mouse model of pre-menopausal breast cancer.

In their study, 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 randomised 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.

They found that 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 stabilised, all mice on study were orthotopically injected with E0771 mammary tumor cells, which model BLBC.

Rossi and her colleagues found that tumour growth in obese mice that had bariatric surgery was statistically equivalent to mice that had maintained a normal weight, but obese mice that lost weight through a low-fat diet had less anti-cancer benefit. Tumour growth in the mice who lost weight by diet mirrored the tumour growth seen in obese mice.

Bariatric surgery weight loss was also linked to lower levels of certain molecular drivers of cancer. Mice that went through surgical weight loss had lower levels of insulin and inflammatory proteins, suggesting that the surgery reduced obesity-linked increases in insulin, inflammation and breast cancer growth.

“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 signalling, which did not occur with non-surgical weight loss despite an equivalent amount of weight and body fat loss in FOb-Diet mice,” the authors concluded. “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. 

"One consequence of the obesity epidemic in the United States and many other countries is increasing rates of obesity-related cancer," said Hursting. "However, we are not going to solve this growing problem through bariatric surgery, which, despite being effective, is too expensive and too difficult to be done on everyone who is obese. Our goal is to understand what the surgery is doing metabolically to slow tumors, and replicate those protective effects through combinations of diet, exercise and possibly drugs that target some of the same pathways as the bariatric surgery."

In addition to Rossi and Hursting, other authors include Laura W Bowers, Subreen A Khatib, Laura A Smith, and Steven S Doerstling of the University of North Carolina at Chapel Hill; and Alfor Lewis and Randy J Seeley of the University of Michigan.

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