gyn oncology obesity project. “obesity is linked as a cause of 20% of cancer deaths in women.”
TRANSCRIPT
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
0
.03
.05
.08
.1
.12
.15
.17
.2
.23
.25
Insu
lin
Sen
siti
vity
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