Weight loss may prevent cancer, reduce mortality for adults with obesity
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Weight-loss interventions may reduce risks for some cancers, cancer mortality and recurrence for people with obesity, according to a speaker at ObesityWeek 2021.
Tanya Agurs-Collins, PhD, RD, program director of the health behavior research branch in the division of cancer control and population sciences at the National Cancer Institute, said some studies have found weight loss may have a protective effect against some cancers and could lower the risk for recurrence, but most of the evidence has come from studies not powered to evaluate associations between weight-loss interventions and cancer-specific outcomes.
“There is a need for long-term randomized clinical trials to evaluate the effects of intentional weight loss on reducing cancer risk, as well as the need to measure body composition instead of just focusing on BMI,” Agurs-Collins said during the presentation.
Obesity increases risk for most cancers
Agurs-Collins described obesity as a disease affecting every part of the cancer control continuum. Men with severe obesity have a 52% higher risk for cancer death and women with severe obesity a 62% higher risk compared with those with normal weight. There is also convincing or probable evidence that weight gain or body fatness increases the risks for 13 types of cancer in adults. A study published in Scientific Reports in 2014 found the risk for breast cancer in postmenopausal women increased with each 1 kg/m2 increase in BMI.
Agurs-Collins said increased inflammation, sex-steroid hormones, growth factors and insulin resistance in obesity all lead to pathways that encourage cancer cell promotion and progression.
“There are opportunities for weight loss to reverse these negative or molecular pathways that influence cancer risk,” Agurs-Collins said. “This suggests that we need weight-loss interventions to reverse these effects.”
Weight loss and cancer risk
Few studies have examined whether changes in body weight are associated with cancer risk. In the Women’s Health Initiative Observational Study, intentional weight loss of 5% or more was associated with a lower overall risk for obesity-related cancer (HR = 0.88; 95% CI, 0.8-0.98) and endometrium cancer (HR = 0.61; 95% CI, 0.42-0.88). A separate analysis pooling prospective studies on diet and cancer showed postmenopausal women could reduce their risk for breast cancer with weight loss of 2 kg or more.
Among observational studies, there is evidence weight loss could reduce cancer risk, but data are lacking regarding weight-loss interventions. In the Look Ahead trial, participants who engaged in intentional lifestyle intervention had a 16% lower risk for cancer at 12 years compared with controls, but the difference was not statistically significant.
“This shows intensive weight loss could lower cancer risk,” Agurs-Collins said. “This is the only randomized controlled trial that examined long-term cancer outcomes in an intensive lifestyle intervention for weight loss, but they only followed them for 12 years and the study was not originally designed to look at cancer risk.”
Bariatric surgery may also lower cancer risk. In a retrospective cohort study, adults with severe obesity undergoing bariatric surgery had a lower risk for all cancers (HR = 0.76; P < .001) and obesity-associated cancers (HR = 0.59; P < .001) compared with matched controls.
Interventions and cancer survival
There is also a lack of studies examining associations between weight loss and cancer survival or recurrence. The Women’s Intervention Nutrition Study randomly assigned 2,437 women with breast cancer to a low-fat diet intervention or control group. The diet group had a mean weight loss of 6 lb and a 24% reduction in breast cancer recurrence, though Agurs-Collins said the study was not designed to examine associations between weight loss and cancer recurrence.
In 2020, a systematic review and meta-analysis assessed how different weight-loss approaches affected breast cancer survivors with overweight or obesity. Twenty studies with 2,208 total participants were included in the meta-analysis. Researchers concluded weight-loss interventions may reduce body weight, BMI and waist circumference, but they could not determine whether weight loss affects the risk for cancer survival or recurrence.
“When you look at overall survival, breast cancer recurrence, disease-free survival or adverse events, they found that either no trial reported these outcomes or there were insufficient studies to do subgroup analysis,” Agurs-Collins said.
Agurs-Collins said the findings reveal a need for large randomized controlled trials designed to test the effect of intentional weight loss for people with cancer before, during and after treatment, by specific cancer site and recurrence. She noted four trials in Italy, Germany, Spain and the U.S. are currently being conducted with women with breast cancer engaging in diet, energy reduction and physical activity interventions.
“These studies are powered to determine the effects of the various dietary weight-loss interventions on breast cancer prognosis and endpoints,” Agurs-Collins said. “We hope that the results will provide evidence that weight-loss interventions can increase survivorship and reduce cancer recurrence.”
References:
- Chlebowski RT, et al. J Natl Cancer Inst. 2006;doi:10.1093/jnci/djj494.
- Luo J, et al. JNCI Cancer Spectr. 2019;doi:10.1093/jncics/pkz054.
- Schauer DP, et al. Ann Surg. 2019;doi:10.1097/SLA.0000000000002525.
- Shaikh H, et al. Cochrane Database Syst Rev. 2020;doi:10.1002/14651858.CD012110.pub2.
- Teras LR, et al. J Natl Cancer Inst. 2020;doi:10.1093/jnci/djz226.
- Yeh H, et al. Obesity. 2020;doi:10.1002/oby.22936.
Perspective
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Epidemiology studies have linked obesity with the risk of developing a number of different cancers and greater cancer mortality. Intentional weight loss through dietary/lifestyle interventions or bariatric surgery has been associated with decreased cancer risk. However, in individuals with cancer, the benefits of intentional weight loss on cancer outcomes are unclear.
At Obesity Week, Dr. Agurs-Collins highlighted the need for large randomized controlled trials to test the impact of intentional weight loss on outcomes for individuals with specific cancer types. A number of studies are ongoing that examine dietary weight-loss interventions on breast cancer outcomes. While lifestyle modification is the backbone of all weight loss strategies, pharmacologic strategies should also be considered, with caution.
Previously, the weight-loss medication locaserin was withdrawn due to its association with increased cancer risk. Concerns have previously been raised regarding GLP-1 receptor agonists and the risk for medullary thyroid and pancreatic cancers. However, preclinical studies suggest that GLP-1 receptor agonists may reduce the progression of certain cancers, and clinical trials have demonstrated their benefit for weight loss over and above dietary/lifestyle interventions.
Therefore, expanding clinical trials and weight-loss interventions will be important to determine their impact on the survival of patients with specific cancer types. These studies are essential given the increased rates of obesity-associated cancer.
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Agurs-Collins T. Epidemiologic evidence linking weight loss and cancer prevention and control. Presented at: ObesityWeek 2021; Nov. 1-5, 2021 (virtual meeting).
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