Commentary by Jennifer Ligibel, MD; Cheryl Rock, RD, PhD; and Clifford Hudis, MD
"An enormous [medical] literature has developed over the last 10 years, showing the association between obesity and cancers," said Jennifer Ligibel, MD, Director of the Leonard P. Zakim Center for Integrative Therapies, Dana-Farber Cancer Institute, and Assistant Professor of Medicine at Harvard Medical School.
Obesity-Cancer: The Studies
Researchers laid out the link as far back as a decade ago in the New England Journal of Medicine,1 Ligibel said. The cohort study followed more than 900,000 men and women for 16 years; all study participants were free of cancer at enrollment in 1982. They found that obesity was linked with multiple cancers, including colon, rectum, liver, gallbladder, pancreas, kidney, stomach, esophagus, breast, uterus, cervix, ovary, and other sites. The researchers concluded that the pattern current then—in 1998—could account for 14% of cancer deaths in men and 20% of those in women. "Since then," she said, ''another 50 reports have shown the same.''1
In a large meta-analysis of 82 studies published in the Annals of Oncology, researchers found that obesity is also linked with poorer overall survival and breast cancer survival. The researchers looked at body mass index (BMI) before diagnosis. Compared to women of normal weight, the relative risk for total mortality was 1.41 obese (BMI>30), 1.07 overweight (BMI 25.0-<30.0), and 1.10 underweight (BMI<18.5) 1.10.2
What isn't known with certainty, said Ligibel and others at the meeting, is whether healthy diets and weight loss can reduce obesity's role in cancer development, recurrence or death. Researchers are feverishly trying to find out. In a report published in JAMA in November 2015, researchers followed more than 4,200 women, ages 60 to 80, with an average BMI of 30 over nearly 5 years. Those who followed a Mediterranean diet with extra virgin olive oil slashed their risk of breast cancer by 68%.3
"The best evidence that weight loss reduces cancer risk comes from bariatric surgery," Ligibel said. In a meta-analysis published in Obesity Surgery, researchers looked at 13 studies. They concluded that bariatric surgery and the resulting weight loss are linked with a reduced cancer risk in morbidly obese people, but suggested the conclusion should be viewed with caution due to study heterogeneity.4
Ligibel hopes to start her BWEL (Breast Cancer Weight Loss study) in spring 2016 to compare health education to health education plus telephone support in more than 3,000 overweight cancer survivors. The purpose of the study is to evaluate if weight loss impacts survival. Other studies are underway or planned.
“Helping cancer patients keep their weight under control is a challenge,” said Cheryl Rock, PhD, RD, Professor in the Department of Family Medicine and Public Health at the University of California at San Diego and at Moores Cancer Center, in La Jolla, CA. Interventions stressing physical activity is one way, but not simple. "The average woman, even if she was active prior to diagnosis, has a difficult time keeping up after,'' Rock said. “With the rigors of treatment, exercise is often the last thing on a woman's mind,” she said.
“Post-treatment weight gain is common,” she said. “The best explanation, besides inactivity, are body composition changes due to treatment and loss of lean body mass, with caloric needs dipping from 1800 to 1300 or so,” she said. “Older women with cancer also tend to have more comorbidities,” she said, making it even less likely they would exercise. "Cancer-related fatigue is a symptom that occurs not just in breast cancer but all cancers," she said.
In her ENERGY (Exercise and Nutrition to Enhance Recovery and Good Health for You) study, Rock and her colleagues showed that an intensive behavioral weight loss intervention focused on exercise and nutrition led to clinically meaningful weight loss in cancer survivors who were overweight or obese. At 12 months, the mean weight loss was 6% of initial weight in the intervention group and 1.5% in the control group receiving less support (P<.001). At 24 months, mean weight loss was 3.7% and 1.3%, still significant.5
Explaining the Obesity-Cancer Link
“Inflammation may drive the increased risk of cancer in those who are obese, at least for breast cancer,” said Clifford Hudis, MD, Chief of the Breast Cancer Medicine Service, Memorial Sloan Kettering Cancer Center. A long-standing hypothesis is that obesity elevates pro-inflammatory mediators such as TNF-alpha, prostaglandin E2 (PGE2) and interleukin 1 beta (Il-1β).
That elevates aromatase expression, which increases estrogen synthesis and blood levels of the hormone, in turn raising the risk of endocrine-receptive positive (ER-positive) breast cancer in post-menopausal women. "Obesity causes a chronic, inflammatory state," Hudis said. However, he added, the inflammation may also be present in normal weight women and perhaps help explain their breast cancer, too.
November 17, 2015
Ligibel J, Rock C, Hudis C. The Obesity-Cancer Link: Forging a Shared Research Agenda. The Obesity Society, ObesityWeek 2015, Los Angeles, CA. November 2-6, 2015.
1. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality form cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003;348:1625-1638.
2. Chan DS, Vieira AR, Aune D, Bandera EV, Greenwood DC, McTiernan A, et al. Body mass index and survival in women with breast cancer—systematic literature review and meta-analysis of 82 follow-up studies. Ann Oncol. 2014;25 (10):1901-1914.
3. Toledo E, Salas-Salvadó J, Donat-Vargas C, Buil-Cosiales P, Esruch R, Ros E, et al. Mediterranean diet and invasive breast cancer risk among women at high cardiovascular risk in the PREDIMED trial. JAMA Intern Med. 2015;175(11):1752-1760.
4. Casagrande DS, Rosa DD, Umpierre D, Sarmento RA, Rodrigues CG, Schaan BD. Incidence of cancer following bariatric surgery: systematic review and meta-analysis. Obes Surg. 2014;24(9):1499-1509.
5. Rock CR, Flatt SW, Byers TE, Colditz GA, Demark-Wahnefried W, et al. Results of the exercise and nutrition to enhance recovery and good health for you (ENERGY) trial. JCO. Oct 1, 2015:3169-3176.