GYN ONCOLOGYOBesity Project

“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

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Insu

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ensi

tivity

0 1 2 3 4 5 6

TNF Alpha (pg/ml)

r = -0.67, p < 0.0001

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