The role of obesity and bariatric surgery-induced weight loss in breast cancer

Abstract

Obesity is a complex metabolic condition considered a worldwide public health crisis, and a deeper mechanistic understanding of obesity-associated diseases is urgently needed. Obesity comorbidities include many associated cancers and are estimated to account for 20% of female cancer deaths in the USA. Breast cancer, in particular, is associated with obesity and is the focus of this review. The exact causal links between obesity and breast cancer remain unclear. Still, interactions have emerged between body mass index, tumor molecular subtype, genetic background, and environmental factors that strongly suggest obesity influences the risk and progression of certain breast cancers. Supportive preclinical research uses various diet-induced obesity models to demonstrate that weight loss, via dietary interventions or changes in energy expenditure, reduces the onset or progression of breast cancers. Ongoing and future studies are now aimed at elucidating the underpinning mechanisms behind weight-loss-driven observations to improve therapy and outcomes in patients with breast cancer and reduce risk. This review aims to summarize the rapidly emerging literature on obesity and weight loss strategies with a focused discussion of bariatric surgery in both clinical and preclinical studies detailing the complex interactions between metabolism, immune response, and immunotherapy in the setting of obesity and breast cancer.

Keywords: Adiposity; Caloric restriction; High fat diet; Immunotherapy; Obesity; PD-L1.

Fig. 1

Common bariatric surgery approaches. Compared with the normal intact stomach, laparoscopic adjustable gastric banding (AGB) maintains the gastric cavity but restricts the fundus and cardia just below the esophagus to slow the rate of feeding and induce more rapid satiety. AGB was widely utilized but has fallen out of favor in the past 5 years due to adverse side effects, such as failure to sustain long-term weight loss, band slippage, and perforation. Roux-en-Y gastric bypass (RYGB) is both a restriction of stomach size leaving only a small pouch, as well as a dramatic rearrangement of the gut with impacts on gut peptides and gastric emptying. RYGB involves division of the upper gastric cavity from the lower, where the remaining duodenal pancreatic and hepatic secretions are diverted free of digesta and are anastomosed at a distal region of jejunum. Vertical sleeve gastrectomy (VSG) involves removal of the fundus and greater curvature portion of the stomach, leaving a sleeve that connects the esophagus to the duodenum. VSG is characterized by increased gastric emptying and hormone changes

Fig. 2

Diet-induced obesity varies by strain and sex. The susceptibility of murine models to diet-induced obesity (DIO) varies based on sex and background strain. C57BL/6 animals are highly obesogenic, where both sexes become obese, but males are more responsive to DIO compared to females with a more rapid and greater extent of adiposity observed. FVB/N animals exhibit highly variable weight gain based on the sex, age, and study in response to DIO. BALB/c animals are DIO-resistant regardless of sex or age

Fig. 3

Benefits of weight loss by lifestyle or surgical intervention. The benefits associate with weight loss through lifestyle modifications or bariatric surgery include alterations in the mammary adipose with decreased hypoxia, insulin resistance, leptin release, and aromatase expression. These changes are associated with alterations in resident and non-resident immune cell populations that may influence the risk of onset and progression in the setting of breast cancer