For Older Women, Exercise May Cut Breast Cancer Risk

For sedentary postmenopausal women, moderate to vigorous exercise for a year reduced levels of estradiol, researchers said.

The reductions, compared with those achieved by controls, were modest but significant and were consistent with a lower risk for breast cancer, according to Christine Friedenreich, PhD, of Alberta Health Services in Calgary, and colleagues.

The finding, from a randomized trial, is evidence that such women -- sedentary and mostly overweight -- can "achieve and sustain high levels of aerobic exercise," the researchers reported online in the Journal of Clinical Oncology.

Observation suggests that increased physical activity is linked to lower breast cancer risk, but exactly how remains unclear, the researchers noted. One plausible mechanism, they said in the journal, is modification of the sex hormones.

To investigate the issue, they enrolled 320 postmenopausal women, ages 50 to 74, in a one-year trial; 160 women were randomly assigned to 225 minutes a week of aerobic exercise, the remaining 160 maintained their usual level of activity.

At baseline, six months, and 12 months, the researchers assessed circulating levels of estrone, estradiol, androstenedione, and testosterone by radioimmunoassay and sex hormone-binding globulin (SHBG) by an immunometric assay.

At the beginning, most of the women were overweight, with an average body mass index of about 29, the researchers said.

The intervention consisted of a monitored, structured program of at least 45 minutes of aerobic exercise five days a week for 12 months at 70% to 80% heart rate reserve. At least three sessions per week were done in a fitness facility with onsite exercise trainers and the remainder were home-based.

On weekly logs, Friedenreich and colleagues found, the exercisers recorded:

• An average of 3.6 sessions a week, for an average exercise duration of 178.4 minutes a week
• An average objectively measured heart rate of 80.1% of the estimated heart rate maximum and 62.2% of the estimated heart rate reserve
• An average estimated energy expenditure of 5.7 metabolic equivalent-hours

At the end of the trial, the researchers found statistically significant reductions in estradiol and free estradiol (with treatment effect ratios of 0.93 and 0.91, respectively) for the exercisers compared with the controls.

They also noted increases in SHBG, with a treatment effect ratio of 1.04, compared with the controls.

After adjusting for weight lost during the program, the changes in estradiol and free estradiol remained significant (at P=0.014 and P=0.006, respectively), but changes in SHBG were no longer significant.

There were no significant differences in estrone, androstenedione, and testosterone levels.

The researchers said the clinical significance of the changes in estradiol is likely to be small but may be of value in women unwilling or unable to take chemoprevention measures.

Indeed, an outside expert cautioned that the study -- although well conducted -- doesn't imply that exercise can reduce estrogen levels by anywhere near the 90% attributed to aromatase inhibitors.

"The modest reduction in estrogen levels seen is unlikely to mediate any major reduction in breast cancer," argued Rowan Chlebowski, MD, PhD, of the Harbor-University of California Los Angeles Medical Center in Torrance, Calif.

That creates a dilemma, he wrote in an accompanying editorial. Although mediators of breast cancer risk that are under lifestyle control have been found, Chlebowski argued, "pharmacologic approaches may be both more potent and more palatable for both patients and health professionals."

Among the trial's strengths, the researchers said, are its large sample size, the long period of supervised exercise, a low dropout rate, and valid measures of estrogens and androgens.

One limitation is the 10% of control volunteers who actually increased their vigorous recreational activity levels by 200 minutes a week or more. The study also had a select sample, the researchers said, adding it's not clear how many women would be able to maintain such an exercise program.

The study and researchers had support from the Canadian Breast Cancer Research Alliance, the Canadian Institutes of Health Research, the Alberta Heritage Foundation for Medical Research, and the Canada Research Chairs Program.

The authors reported no potential conflicts.

Chlebowski reported financial links with AstraZeneca, Novartis, Pfizer, and Amgen.

Primary source: Journal of Clinical Oncology Source reference: Friedenreich CM, et al "Alberta physical activity and breast cancer prevention trial: Sex hormone changes in a year-long exercise intervention among postmenopausal women" J Clin Oncol 2010; DOI: 10.1200/JCO.2009.24.9557.Additional source: Journal of Clinical OncologySource reference: Chlebowski RT "Lifestyle and breast cancer risk: The way forward?" J Clin Oncol 2010; DOI: 10.1200/JCO.2009.26.7898.