WASHINGTON, DC—As the number of cancer survivors—now more than 12 million strong—continues to mount, researchers are examining ways of lowering the risk of recurrence and understanding the factors contributing to increased survival. A workshop here sponsored by the National Cancer Policy Forum of the Institute of Medicine targeted the harmful effects of obesity and the ways to reduce it in this population. A summary report of the IOM obesity workshop is planned for the spring.
The purpose of the workshop was to improve the outcome for the growing number of obese patients with cancer, said Wendy Demark-Wahnefried, PhD, RD, Chair of the workshop planning committee, an NCPF member, and Professor and the Webb Endowed Chair of Nutrition Sciences and Associate Di-rector for Cancer Prevention and Control at the University of Alabama Comprehensive Cancer Center.
“There are two very important confluent trends that are occurring today: aging and obesity,” she noted, adding, “Our older population is getting fatter.”
These trends are especially troubling given that cancer rates go up with aging. In fact, said Patricia A. Ganz, MD, Director of the Division of Cancer Prevention and Control Research at the Jonsson Comprehensive Cancer Center, some 60% of the estimated 12 million cancer survivors are currently over age 65. In addition, about 14% of these survivors were diagnosed more than 20 years ago; and the current average age of male cancer survivors is 69 and the average age of female cancer survivors is 64.
Dr. Ganz, a member of the workshop planning committee and the ASCO representative to the IOM, is Vice-Chair of the National Cancer Policy Forum and served on the IOM committee responsible for the seminal 2005 report on cancer survivors' unmet needs (“From Cancer Patient to Cancer Survivor: Lost in Transition” (OT, 12/10/05).
“Cancer survivors want to do whatever they can to maximize their health and recovery,” she said. “Prevention of weight gain requires increased physical activity, which in itself has health benefits.”
There is a pressing need to help cancer survivors shed unwanted pounds, as shown in a recent study of weight gain and risk in 9,105 survivors of breast, prostate, colorectal, bladder, and uterine cancers and melanoma cited by Cindy L. Carmack et al in an article in the October 2011 issue of Cancer Epidemiology, Biomarkers & Prevention (2011;20:2068-2077). The paper notes that weight gain is emerging as a harmful prognostic factor not only for the more common cancers, but also for testicular cancer and childhood brain tumors as well as acute lymphoblastic leukemia (ALL) treated with cranial radiation.
In fact, workshop speakers noted that published studies have shown that increased body weight is associated with increased death rates for all cancers combined and for cancers at multiple specific sites, as was shown in a major prospective study published in The New England Journal of Medicine in 2003.
“There is growing evidence that obesity increases the risk of cancer at many organ sites,” said another speaker, Susan M. Gapstur, PhD, MPH, Vice President for Epidemiology at the American Cancer Society. “Hormones, growth factors, and inflammation are likely the major mechanisms.”
While scientists don't completely understand the health effects of a lifetime of being obese, Dr. Gapstur noted that they do know that obesity is second only to tobacco as a leading risk factor for cancer, and that future research “should focus on how risk is affected by successful (sustained) weight loss.”
But, Dr. Gapstur told OT, “Lifestyle changes are very, very difficult” for anyone, including cancer patients, to make. The ACS is currently in the process of updating its published guidelines on nutrition and physical activity for cancer survivors.
Complicating the obesity/cancer link is that cancer survivors often have other weight-related diseases, a point made by another member of the IOM obesity workshop planning committee, Rachel Ballard-Barbash, MD, MPH, Associate Director of the Applied Research program in the Division of Cancer Control and Population Sciences at the National Cancer Institute.
Obesity-related comorbid conditions are common among cancer patients and are likely to increase in the future, especially among older adults, she said. “Unfortunately, treatment may be less intensive among people who are older, obese, and have comorbid diseases — many of which are increasing with obesity, physical inactivity and poor diet,” she stressed.
Type 2 Diabetes
An issue repeatedly raised at the workshop was the association between cancer and one common comorbid condition—type 2 diabetes, now epidemic in the United States.
There was general agreement that obesity and type 2 diabetes are associated with an increased risk of cancer and cancer-related deaths. Obesity and the insulin resistance syndrome (metabolic syndrome) are linked to physiological alterations such as systemic inflammation, an altered adipokine profile, hyperinsulinemia, hyperglycemia, and a prothrombotic state—all of which raise the risk for cancer, said another member of the workshop planning committee, Pamela J. Goodwin, MD, MSc, Senior Scientist at the Samuel Lunenfeld Research Institute and the Marvelle Koffler Chair in Breast Research at the University of Toronto.
As increasing obesity rates have spiked a rise in type 2 diabetes, so they have also “contributed to increased breast cancer risk and adverse breast cancer outcomes.” She added, “Lifestyle interventions leading to weight loss and/or enhanced physical activity could potentially reverse these effects.”
New Cancer Treatment & Risk-Reduction Possibilities Related to Metformin
The type 2 diabetes/cancer link has raised new cancer treatment and risk-reduction possibilities involving the diabetes drug metformin, said Derek LeRoith, MD, PhD, Director of Research in the Division of Endocrinology, Diabetes and Bone Diseases at Mount Sinai School of Medicine.
“Epidemiological studies have shown that patients with diabetes treated with metformin have a lowered cancer risk than those treated with sulfonylureas or insulin,” he said. “One possibility is that metformin improves metabolism and reduces insulin resistance and hyperinsulinemia; another possibility is that metformin directly inhibits cancer cell proliferation, via activation of AMPKinase. Indeed, the effects have been so impressive that trials are ongoing to use metformin as neoadjuvant and adjuvants to chemotherapy in women with breast cancer.”
Speaker after speaker agreed with Dr. Gapstur that weight loss through dietary and exercise interventions is very difficult for cancer survivors to achieve. Bariatric surgery for obese patients is one effective but controversial weight loss option discussed in detail at the IOM workshop.
“Weight loss following bariatric surgery reduces cancer incidence and mortality; it is reasonable to hypothesize that the molecular phenomena responsible also contribute to survival among cancer patients,” said Bruce M. Wolfe, MD, Professor of Surgery at Oregon Health & Science University, Co-Chair of the NIH Research Consortium on Bariatric Surgery and Immediate Past President of the American Society for Metabolic and Bariatric Surgery.
Dr. Wolfe shared data from a Utah study showing that weight loss following bariatric surgery can decrease the risk of cancer as a cause of death by as much as 60%.
Asked by OT at what point the risks of undergoing bariatric surgery are offset by its benefits in obese cancer patients, Dr. Wolfe—who has participated in about 1,000 bariataric surgical procedures – said that there are no specific data on bariatric surgery in cancer survivors.
“It's still considered scary and a not widely used intervention,” he noted, but he said the mortality rate has been “dramatically reduced” in the last five years and is now very low.
He said that guidelines published in an NIH consensus statement in 1991 (and now in the process of being updated) define the best candidates for bariatric surgery. Generally, a candidate will have a body mass index (BMI) of 40 or greater. While bariatric surgery is effective for the very obese,
“Hopefully in the future there will be other effective means of weight loss,” he said.
In an overview of interventions for obese adults, Thomas A. Wadden, PhD, Professor of Psychology in the Department of Psychiatry at the Perelman School of Medicine at the University of Pennsylvania, noted that the new goal of weight loss management in overweight and obese patients is to achieve an initial reduction in body weight of about 10%. Even a moderate weight loss in this range can significantly decrease the severity of obesity-associated risk factors, he said.
Lifestyle modification for weight control requires new habits, but “new habits can be learned in the same manner as a sport or a musical instrument,” Dr. Wadden emphasized.
Currently approved weight-loss drugs are effective for helping obese patients shed pounds, said Dr. Wadden, but ideally they should be combined with behavioral measures.
Major Unresolved Issues
“Does adding weight loss medication improve the results of behavioral treatment? Yes,” he said. “Does adding behavioral treatment improve the results of pharmacotherapy? Yes.” But, Dr. Wadden noted, there are major unresolved issues in the management of obesity that may affect cancer survivors, including:
- Who will receive weight management services?
- Who will pay for treatment?
- Who will provide obesity treatment?
- How will treatment be delivered?
And finally, how can the development of overweight and obesity be prevented?