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OBesity Project GYN ONCOLOGY “Obesity is linked as a cause of 20% of cancer deaths in women.” Obesity and Cancer • Obesity is a risk factor for numerous cancers • Esophageal • Pancreatic • Colorectal • Postmenopausal breast • Endometrial • Ovarian • Renal Mechanisms of Increased Cancer Risk • Increased female hormone exposure • Excess Insulin • Induction of inflammation • Turning on of Onco-genes Relationship Between Insulin Sensitivity and Cytokines Insulin Sensitivity .25 .23 .2 .17 .15 .12 .1 r = -0.67, p < 0.0001 .08 .05 .03 0 0 1 2 3 4 5 6 TNF Alpha (pg/ml) Kirwan, Diabetes; 2002 Incidence of Cancer Related to Obesity • Breast Cancer (230,480 female US cases yearly) • Increase circulating estradiol level is a risk factor for the development of postmenopausal breast cancer • Estrogen modulating hormones (SERMs) have been shown to decrease the development of breast cancer Obesity and Cancer • Endometrial Adenocarcinoma (46,470 US cases yearly) • Increase in unopposed Estrogen • Increase in Endometrial Hyperplasia • Approx. 25% of Complex Atypical Hyperplasia (CAH) becomes Invasive AdenoCA, the most prevalent form of Endometrial CA Obesity and Cancer • Overweight and obese women have a 3.5x risk for development of Endometrial Cancer relative to normal weight controls • Other risk factors for Endometrial Cancer are HTN and DM, which are associated with obesity Obesity and Cancer • Ovarian Cancer (21,990 US cases yearly) • Two-fold increase in risk in obese older women who have never taken postmenopausal hormones Obesity and Cancer • Colon Cancer (52,400 female US cases yearly) • Higher amounts of glucose have been associated with subsequent risk of colon cancer • Increased hyperinsulinemia and production of insulin-like growth factor are possible agents leading to the increased risk of colon cancer Obesity and Cancer • Esophageal Cancer (3,530 female US cases yearly) • Recent evidence suggests a shift to increased rates of adenocarcinoma compared to squamous cancers • Increased esophageal reflux with increased inflammation as the possible pathway Obesity and Cancer • Weight loss can reduce the incidence of cancer • Two large cohort studies from Sweden and the U.S. suggest a lower cancer incidence as well as decreased risk of death in women undergoing bariatric surgery compared to BMI-matched controls • Observational data also has demonstrated that weight loss is associated with reduction of risk for certain cancers including breast cancer Obesity and Cancer • Studies evaluating weight loss and weight gain and survival following a diagnosis of cancer • Survival after Endometrial CA reduced in Obese women • Physical activity after diagnosis may reduce the risk of breast cancer recurrence • Trial for women diagnosed with breast cancer showed longer disease-free survival times for those who lost more weight through intervention with diet and physical activity than the control group Diagnosis and Treatment of Cancer with Obesity • Obesity affects the detection and treatment of cancer • Obese less likely to receive routine cancer screening tests • More likely to postpone preventive examinations • Impacts treatment planning • Surgery • Radiation therapy • Chemotherapy Diagnosis and Treatment of Cancer with Obesity • Risks of surgery are increased by obesity • Operative time • Blood loss • Thromboembolic complications • Pneumonia • Wound infection • Operative site infection Diagnosis and Treatment of Cancer with Obesity • Optimal delivery of radiation and chemotherapy are affected by obesity • Chemotherapy: • Dosing of therapy may be affected by weight in heavier cancer patients • Concerns about high doses of chemotherapy leading to greater toxicity • Obese patients may not receive optimal dose intensities compared to nonobese patients • Radiation therapy: • Target location may be altered and hamper receiving full doses Diagnosis and Treatment of Cancer with Obesity • Many women are unaware of the link of obesity and increased cancer risk • Burden of obesity demands increased attention in order to improve cancer prevention and treatment