The analysis of over 61,000 women from the Women’s Health Initiative (WHI) Observational Study also found that while not associated with overall risk, a weight gain of 5% or more correlated with a 54% higher incidence of triple-negative breast cancer, Rowan Chlebowski, MD, PhD, of City of Hope National Medical Center in Duarte, California, and colleagues reported in Cancer.
Although obesity has been strongly related to breast cancer risk, previous studies on whether weight loss might reduce postmenopausal risk have yielded mixed results, according to background information in the study.
Chlebowski said that the new findings are in line with evidence from the WHI Dietary Modification trial, in which breast cancer patients randomized to a low-fat diet had a statistically significant but modest weight loss (3%) that was associated with improved overall survival compared with women in a usual-diet comparison arm.
“Referral to appropriate interventionists and dietitians for postmenopausal women with diagnosed breast cancer seems a reasonable course to recommend,” he said.
In the WHI Observational Study, participants ranged in age from 50 to 79 years at baseline, had no history of breast cancer, and had normal mammogram results. About 85% were white. Demographic characteristics were documented, and body weight, height, and body mass index (BMI) were assessed at entrance and once again 3 years later.
Participants were divided into four analysis categories: stable weight, weight gain, weight loss intentional, and weight loss unintentional (since unintended loss can indicate morbidity or change in socioeconomic status).
With an average follow-up of 11.4 years, there were 3,061 incident cases of invasive breast cancer. The mean time from year 3 weight determination to diagnosis was 6.47 years (range 0.005-17.0 years). Most early weight loss was maintained through year 6.
In the 8,175 women experiencing weight loss, the HR for risk of breast cancer was 0.88 (95% CI 0.78-0.98, P=0.02) compared with the 41,139 stable-weight counterparts, with no interaction observed by BMI. Adjustment for mammography did not alter these findings. No significant differences emerged by intended or unintended weight loss.
In terms of the type of weight loss, compared with the stable group, women who had intentional weight loss were more likely to have a higher BMI and less likely to be physically active or to have used menopausal hormone replacement therapy (P<0.01).
For the 4,829 women reporting intentional weight loss, the mean loss from baseline to year 3 was 19.56 pounds (standard deviation 27.12); the mean weight loss for the 3,346 reporting unintentional weight loss was 16.90 pounds (SD 18.69).
Compared with the stable group, women with a weight gain of at least 5% (n=12,021) were more likely to be younger, black, heavier smokers, and younger at the birth of their first child. As for the interesting association of weight gain with triple-negative breast cancer (HR 1.54, 95% CI 1.16-2.05), the possible causative factors are unclear.
“While hormone-related changes may play a role, it is more likely that other factors associated with obesity such as markers of inflammation and components of the metabolic syndrome are playing a bigger role,” Chlebowski said. Absent of a strong biological rationale for this correlation, it should be interpreted with caution.
“As you can see from the study, there was no interaction by weight, and the hazard ratio was less than 1 in women who were not obese, so I think losing a few pounds probably would be beneficial even for the women who will have normal weight,” Chlebowski said. In his view, these data combined with the evidence from the randomized dietary trial send a strong signal that weight loss may also benefit postmenopausal women with established breast cancer.
Chlebowski is a consultant for AstraZeneca, Novartis, and Pfizer. No other authors reported conflicts.