Increased weight increases risk, so losing weight decreases risk. Wrong!

A new study "challenges the simple suggestion that patients who are overweight or obese should just lose weight to reduce their cancer risk," say experts. The findings were published online June 10 in JAMA Oncology.

"Weight control, when achieved, may be very effective for many weight-associated illnesses and ailments, but the data suggesting it will reduce an already elevated risk for breast cancer are limited," write Clifford Hudis, MD, chief of Breast Medicine Service at Memorial Sloan Kettering Cancer Center, and Andrew Dannenberg, MD, professor of medicine at Weill Cornell Medical College, both in New York City, in an accompanying commentary.

The comments were prompted by a study of 67,000 postmenopausal women that showed that obesity was associated with an increased risk for invasive breast cancer, more advanced disease, and increased risk for death after diagnosis, but weight loss during the study period did nothing to lower cancer risk.

The study was conducted by Marian L. Neuhouser, PhD, RD, a nutritional epidemiologist at the Fred Hutchison Cancer Research Center in Seattle, and colleagues. They studied data from women aged 50 to 79 years participating in the Women's Health Initiative, which included a hormone therapy trial and a dietary modification trial. Height and weight were taken at study enrollment and weight was measured annually. Breast mammograms were conducted annually and biennially.

The researchers found a linear trend of increasing breast cancer risk with increasing weight. Women with a body mass index (BMI) greater than 35 kg/m² were at a nearly 60% greater risk for invasive best cancer compared with women with a BMI of 25 kg/m² (hazard ratio [HR], 1.58). A BMI of 35 kg/m² or higher was strongly associated with the risk for estrogen receptor (ER)-positive and progesterone-receptor-positive breast cancers (HR, 1.86), but not with ER-negative cancers. A BMI of 35 kg/m² doubled the risk for larger tumor size (HR, 2.12; P = .02), positive lymph nodes (HR, 1.89; P = .06), regional and/or distant stage (HR, 1.94; P = .05), and breast disease mortality (HR, 2.25; P < .001). Mortality after breast cancer showed an increased association at all obesity levels, with an HR of 1.37 for a BMI of 30 kg/m² to <35 kg/m², and an HR of 2.11 for a BMI 35 kg/m² and over.

Obesity is associated with likely poor prognosis.

Women with a baseline BMI of less than 25 kg/m² who gained more than 5% of body weight during follow-up increased breast cancer risk by more than a third (HR, 1.36). Dr. Neuhouser said in an author interview posted on JAMA Oncology that this suggests that "gaining weight in the immediate postmenopausal period may be a risk that we haven't really considered before."

The research also showed that losing weight after baseline did not lower the breast cancer risk. "We can't just say heavier people have to diet and lose weight," Dr. Hudis commented on JAMA Oncology. "That doesn't mean these patients can't do better. It just means we don't necessarily yet have evidence of how to help them do better."

In their commentary, Drs Hudis and Dannenberg note that obesity rates are likely to increase, with some predictions suggesting that more than 60% of adults in many states will be in the highest BMI category by 2030. What's needed now, they write, are clinical trials to determine if body composition changes and weight loss can lessen cancer risk, research into the roles of calorie restriction, dietary composition, and exercise programs, and a better understanding of why obesity and overweight increases the risk for several cancers, including gastrointestinal and prostate cancer and the recently reported Hodgkin`s lymphoma.

They propose a role for white adipose inflammation in cancer development. "Our findings for white adipose inflammation are consistent with the observations of Neuhouser et al in that we provide a plausible explanation for activation of estrogen receptor signalling after menopause and linked to elevated BMI," they write.

Study author Rowan Chlebowski reports receiving speaker fees and honorarium from Novartis; and honorarium for advisory board and consulting with Novartis, Novo Nordisk, Pfizer, Genentech, and Amgen. Dr Hudis and Dr Dannenberg have disclosed no relevant financial relationships.

JAMA Oncol. Published online June 11, 2015. Abstract, Commentary