Breast Cancer–Related Benefits of Weight Loss

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Anne May, PhD

Melinda Irwin, PhD, MPH

Compared with diet-induced weight loss, equivalent weight loss by exercise had, in addition to positive effects on breast cancer–related sex hormones, more beneficial effects on body composition, including more body fat loss and more lean mass preservation as well as better physical fitness.

—Anne May, PhD

Obesity and physical inactivity are associated with an increased risk of developing and dying of breast cancer via several proposed mechanisms. Two studies presented at the 2014 ASCO Annual Meeting explored the relationships among exercise, weight loss, and breast cancer risk. One study was conducted in healthy postmenopausal women (SHAPE2),1 and the other, in breast cancer survivors (LEAN).2

SHAPE-2 Study

SHAPE-2 was designed to compare the effects of a calorie-restricted diet vs exercise on parameters beyond weight loss. A current review of 19 cohort and 29 case-control studies showed strong evidence for an inverse association between physical activity and postmenopausal breast cancer, with risk reductions ranging from 20% to 40%.

Both exercise and diet achieved similar weight loss, and breast cancer-related sex hormones were positively affected, but exercise appears to exert more beneficial effects on body composition and fitness.

“Compared with diet-induced weight loss, equivalent weight loss by exercise had more beneficial effects on body composition, including more body fat loss and more lean mass preservation as well as better physical fitness,” said lead investigator Anne May, PhD, Assistant Professor at the Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, the Netherlands.

SHAPE-2 enrolled 243 inactive, overweight, nonsmoking postmenopausal women from the Netherlands. After a 4- to 6-week run-in period during which participants followed a standardized diet, participants were randomly assigned to a diet group (n = 97), an exercise-plus–small caloric restriction group (n = 98), or a control group with the goal of maintaining stable weight (n = 48). The study period was 16 weeks.

The diet intervention entailed caloric reduction of 500 kcal per day. The exercise intervention consisted of 4 hours of vigorous resistance and endurance exercise per week plus caloric intake reduced by 250 kcal per day. The goal of both interventions was a weight loss of 5 to 6 kg. Control participants were instructed to maintain their body weight.

The primary outcome measure was change in serum levels of sex hormones at 16 weeks. Both intervention groups had similar demographic characteristics, with a mean age of 60 years and mean body mass index of 29 kg/m2. Both interventions met the primary endpoint for weight loss compared to controls (P < .001), while weight remained stable in the control arm.

Both interventions also achieved significant reductions in serum estradiol, free estradiol, and serum testosterone, and an increase in sex hormone–binding globulin compared with controls (P < .025). But when findings were adjusted for the percentage change in body fat, the effects were attenuated or eliminated.

Patients who exercised showed significantly greater changes compared with the diet-alone group for body weight, body fat, lean mass preservation, and physical fitness as measured by peak VO2 levels (all P < .001).

LEAN Study

The Lifestyle, Exercise, and Nutrition (LEAN) study explored the effects of weight loss on inflammatory and metabolic biomarkers in breast cancer survivors. Interestingly, LEAN showed that patients assigned to counseling as well as those just given a brochure lost some weight, although weight loss was more substantial in the counseling groups.

Senior author and principal investigator of the LEAN study, Melinda Irwin, PhD, MPH, Associate Professor of Epidemiology at Yale School of Public Health, New Haven, Connecticut, observed that motivation to lose weight appears to be an important factor for success. “All the women who entered the study were motivated, and women in the intervention group and those in the usual-care group both lost weight,” she said.

LEAN enrolled 100 overweight or obese breast cancer patients; 33 were assigned to usual care and were presented with American Institute for Cancer Research nutrition and activity brochures as well as one 30-minute counseling session at 6 months. The other 67 women were assigned to 11 30-minute weight loss counseling sessions over 6 months (33 women in person and 33 women by telephone). The goal of the intervention was 10% weight loss, 150 minutes of physical activity per week, and 10,000 steps per day.

Fifty-two women (78%) completed the interventions, compared with 29 women (88%) in the usual-care group. Mean age was 59 years, and all participants were overweight, physically inactive, highly educated, postmenopausal, and had a mean time since diagnosis of 2.8 years. Most women were non-Hispanic white, had stage I to II breast cancer, and were taking hormone therapy.

Weight loss was achieved in both groups. Women in the intervention group (whether counseled by phone or in person) lost significantly more weight than those in the usual-care group (6% weight loss vs 2% weight loss, respectively).

Because similar results were seen for both in-person and telephone counseling, both groups were pooled for analysis of effects of weight loss on biomarkers. The diet groups achieved a 30% decrease in C-reactive protein (a marker of inflammation), compared with 1% in the usual-care group. Women in the dietary intervention groups also had greater decreases in insulin, glucose, leptin, tumor necrosis factor–alpha, and increases in adiponectin, interleukin-6, and insulin-like growth factor–1 compared with usual care. Women who lost more than 5% of body weight had more beneficial changes in these factors than women who lost less than 5% of body weight. ■

Disclosure: Drs. May and Irwin reported no potential conflicts of interest.


1. May AM, van Gemert W, Peeters P, et al: Effects of equivalent weight loss, with or without exercise, on sex hormones related to breast cancer risk in postmenopausal women: The SHAPE-2 trial. ASCO Annual Meeting. Abstract 1504. Presented May 31, 2014.

2. Loftfield E, Harrigan M, Li F, et al: Effect of weight loss intervention on inflammatory and metabolic markers in breast cancer survivors: The lifestyle, exercise, and nutrition (LEAN) study. ASCO Annual Meeting. Abstract 1505. Presented May 31, 2014.

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