By Molly Brewer, DVM, MD, MS
Professor and Chair, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Connecticut Health Center, Farmington
Dr. Brewer reports no financial relationships relevant to this field of study.
SYNOPSIS: Obesity is a major risk factor for endometrial cancer as well as for other major comorbidities.
SOURCE: Papatla K, Huang M, Slomovitz B. The obese endometrial cancer patient: How do we effectively improve morbidity and mortality in this patient population? Ann Oncol 2016;27:1988-1994.
Endometrial cancer is the fourth most common cancer for U.S. women and is one of the first malignancies to be clearly linked to obesity.1,2 Obesity, defined as a body mass index (BMI) > 30 kg/m2, has been found in more than 80% of women with endometrial cancer.3 In 2015, there were approximately 54,870 new cases of endometrial cancer diagnosed and 10,170 deaths, and in 2016, the number rose to approximately 61,380 cases and 10,920 deaths. The incidence is increasing steadily and mirrors the incidence of obesity.3
Papatla et al reviewed the background of obesity and endometrial cancer. Insulin resistance and hyperinsulinemia are key drivers in the etiologic pathway of endometrial cancer. Hyperinsulinemia increases androgen production, which is converted to estrogen by the large amount of adipose tissue present in obese women, resulting in a hyper-estrogenic state that is unopposed by progesterone. This hyper-estrogenic state drives proliferation of the endometrium and results in histologic changes consistent with endometrial hyperplasia or endometrial adenocarcinoma. Polycystic ovarian syndrome, characterized by chronic oligoovulation, hirsutism, and obesity, is a leading risk factor for the development of endometrial pathology. Not only does obesity predispose a woman to developing endometrial cancer, it is thought to affect tumorigenesis and tumor progression through insulin resistance and hyperinsulinemia, through increased bioavailability of steroid hormones, and through localized inflammation.4,5 In addition, obesity is a risk factor for recurrence and death from endometrial cancer. Other comorbidities, such as cardiovascular disease, which is also associated with an elevated BMI, is the major cause of mortality in women who are 10 years post-diagnosis of endometrial cancer, not the cancer itself.6
Who can best influence the impact of obesity on health? Data reveal that physicians play a key role in influencing health habits in women. In a study by Clark et al, only 29% of patients reported ever being told about a relationship between obesity and endometrial cancer. However, despite this, more than 50% of the women reported trying to lose weight through lifestyle changes after their diagnosis. The patients who were most likely to make lifestyle modifications were the women who had received adequate counseling by a physician.7 According to Cogswell et al, 55% of obstetrician-gynecologists reported that they usually counsel patients on physical activity, and 48% noted that they have prescribed weight loss medications. In addition, 33% reported that they counseled patients on weight control during most visits, but many providers indicated they believed their patients would not follow their weight loss advice.8 Studies have shown that the most effective approach to improving the health of obese patients may be with nutritional counseling and referral to an exercise program. Exercise is one of the major deterrents to obesity-associated diseases and cancers. Unfortunately, the uptake of this behavior in obese women is poor.9
Obesity has become one of the major risk factors for disease in the United States, including cardiovascular disease, diabetes, and cancer death. In addition, emerging literature in breast and colon cancer suggests that obese and inactive patients have a higher mortality than those who are thinner and more physically active. In 1962, obesity affected approximately 13% of the population. Since that time, the incidence has steadily increased. The obesity percentages for the overall U.S. population were 19.4% in 1997, 24.5% in 2004, 26.6% in 2007, and 33.8% (adults) and 17% (children) in 2008.3,10 In 2010, the Centers for Disease Control and Prevention reported that 35.7% of American adults and 17% of American children were obese.3
COMMENTARY
Obesity is a significant health problem, and rates of adults with BMI > 30 kg/m2 continue to increase. The majority of women (63.4%) are overweight or obese and the incidence of endometrial cancers parallels this rise.
Historically, most endometrial cancers were Grade I and Stage I and were cured with surgery alone. With growing rates of obesity and BMIs skyrocketing to levels > 50 kg/m2, we are seeing not only an increase in incidence but also an increase in mortality with endometrial cancer, suggesting that an elevated BMI is also an independent risk factor for worse disease. It is incumbent on healthcare providers to counsel their patients on the many risks associated with obesity, including endometrial cancer. Exercise is the best antidote for obesity and carefully counseling patients on the benefits of exercise and consideration of referral to behavior modification programs may be more important than doing their pap smear, given that endometrial cancer is six-fold more common than cervical cancer.
REFERENCES
- Wiseman M. The second World Cancer Research Fund/American Institute for Cancer Research expert report. Food, nutrition, physical activity, and the prevention of cancer: A global perspective. Proc Nutr Soc 2008;67:253-256.
- Wynder E, Escher G, Mantel N. An epidemiological investigation of cancer of the endometrium. Cancer 1966;19:489-520.
- Centers for Disease Control and Prevention. Adult Obesity Facts. Available at: https://www.cdc.gov/obesity/data/adult.html. Accessed May 1, 2017.
- Calle EE, Kaaks R. Overweight, obesity and cancer: Epidemiological evidence and proposed mechanisms. Nat Rev Cancer 2004;4:579-591.
- Dossus L, Lukanova A, Rinaldi S, et al. Hormonal, metabolic, and inflammatory profiles and endometrial cancer risk within the EPIC cohort--a factor analysis. Am J Epidemiol 2013;177:787-799.
- Ward KK, Shah NR, Saenz CC, et al. Cardiovascular disease is the leading cause of death among endometrial cancer patients. Gynecol Oncol 2012;126:176-179.
- Clark LH, Ko EM, Kernodle A, et al. Endometrial cancer survivors’ perceptions of provider obesity counseling and attempted behavior change: Are we seizing the moment? Int J Gynecol Cancer 2016;26:318-324.
- Cogswell ME, Power ML, Sharma AJ, Schulkin J. Prevention and management of obesity in nonpregnant women and adolescents: Beliefs and practices of U.S. obstetricians and gynecologists. J Womens Health (Larchmt) 2010;19:1625-1634.
- von Gruenigen V, Frasure H, Kavanagh MB, et al. Survivors of uterine cancer empowered by exercise and healthy diet (SUCCEED): A randomized controlled trial. Gynecol Oncol 2012;125:699-704.
- Centers for Disease Control and Prevention. Early Release of Selected Estimates Based on Data From the January-June 2007 National Health Interview Survey. Available at: https://www.cdc.gov/nchs/data/nhis/earlyrelease/200712_06.pdf. Accessed May 1, 2017.
Obesity is a major risk factor for endometrial cancer as well as for other major comorbidities.
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