Modest Weight Loss Cuts Postmenopausal Breast Cancer Risk

Liam Davenport

December 11, 2017

SAN ANTONIO ― Postmenopausal women who lose a relatively modest amount of weight significantly reduce their risk of developing breast cancer compared to those whose weight remains stable, the results of a data analysis suggest.

The findings in more than 60,000 women reported here at the San Antonio Breast Cancer Symposium (SABCS) 2017 revealed that women who lost just 5% of their body weight over 3 years experienced a 12% reduction in their relative risk of developing breast cancer compared wto those who stayed at the same weight.

Lead researcher Rowan Chlebowski, MD, PhD, research professor in the Department of Medical Oncology and Therapeutics Research at the City of Hope National Medical Center in Duarte, California, said in a release: "In the 3-year window of the study, relatively modest weight loss was associated with significant lowering of breast cancer incidence.

Dr Rowan Chlebowski

"From this study, we have evidence that a weight-loss strategy can be effective in lowering breast cancer risk in postmenopausal women," he added.

Dr Chlebowski told Medscape Medical News that the message from the study is "very hopeful," inasmuch as women "don't have to go to normal weight." He added that it "should be encouraging to people to have these modest targets, which should be more easily achievable."

C. Kent Osborne, MD, codirector of the SABCS and director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston, Texas, who was not involved in the study, told an audience of reporters at a press conference that he believes the findings are "going to be helpful."

He said: "I hope you can present this to general doctors rather than to oncologists, because those are the ones seeing normal people, by and large."

I hope you can present this to general doctors rather than to oncologists. Dr C. Kent Osborne

Dr Osborne noted that most of his patients are overweight and that he has always suggested that they lose weight. In the past, he offered such advice because, among other factors, losing weight lowers the risk of developing diabetes.

"Now, we can do it because we have a breast cancer endpoint that suggests that losing weight will help with that as well, so I think that's an important contribution."

Speaking to Medscape Medical News, Dr Chlebowski said that "it's been see obesity be so strongly associated with breast cancer risk and yet have the big analyses unable to show that losing weight will be beneficial."

He pointed out that even the International Association for Research on Cancer, in a recent statement, limited their advice to saying that women should "avoid body fatness."

"That's very discouraging, because it means that if you're overweight or fat, it's too late," Dr Chlebowski said. He noted that a likely reason that previous studies have been unable to show a benefit from weight loss with respect to breast cancer risk is because of study design.

A WHI Study

Dr Chlebowski and colleagues analyzed data from the Women's Health Initiative Observational Study, which involved 93,676 postmenopausal women aged 50 to 75 years who were recruited from 40 clinical centers in the United States between 1993 and 1998. The participants' survival was anticipated to be 3 years.

For the current analysis, the team investigated demographic factors, medical history, breast cancer risk factors, medication use, baseline data, and frequency of mammography examinations.

The final cohort included 61,335 women who had no history of breast cancer and whose mammography results were normal. Of those participants, 41% were of normal weight, 34% were overweight, and 25% were obese at baseline.

Height and weight were measured at baseline and at year 3, and weight change at year 3 relative to baseline was calculated. Participants were stratified on the basis of those whose weight was stable (≤5% weight change), whose who gained weight (≥5% increase), and those who lost weight (≤5% decrease).

"We took the 5% decrease because this level has been shown to change some biochemical markers potentially associated with cancer," Dr Chlebowski told the press conference attendees.

"It's also been shown, in a different study population ― a randomized trial ― to reduce the frequency of diabetes.... So I think the unique thing is we have a very tight window of weight change over a 3-year period of time."

At year 3 of the study, the investigators asked the participants whether they had gained or lost ≥5 pounds and whether the weight change was intentional or unintentional.

Overall, 41,139 women's weight was stable, with a mean change in weight of +0.54 pounds from years 1 to 3. A further 12,021 women experienced weight gain, at a mean change of +18.51 pounds; 4829 participants experienced intentional weight loss, at a mean change in weight of -19.58; and 3346 experienced unintentional weight loss, at a mean change in weight of -16.90 pounds.

Women who experienced weight gain were significantly more likely to be younger, black, and to be heavier smokers (for all, P < .01). Those who experienced weight loss were significantly more likely to have a higher body mass index and were less likely to be physically active (for both, P < .01).

"It's almost a paradox in the population," Dr Chlebowski commented. "Interestingly, the body mass index of this group was 29.9 kg/m2, so then on the verge of going into obesity. So we wondered in retrospect whether that was a motivating factor for them."

During a median follow-up of 11.4 years, there were 3061 incident cases of invasive breast cancer.

Multivariate analysis showed that, compared to women with stable weight, those who experienced weight loss were at significantly lower risk of developing breast cancer, at a hazard ratio (HR) of 0.88 (P = .02).

The findings were not affected by adjusting for mammography frequency, and there was no significant difference in the incidence of breast cancer between women whose weight loss was intentional and those whose weight loss was unintentional (HR, 0.91 and 0.82, respectively; P = .2).

The team found that, although women who gained weight were not at increased risk of developing breast cancer compared to women whose weight was stable (HR, 1.02), they were at significantly higher risk of developing triple-negative breast cancer (HR, 1.54).

During a discussion of the findings, Dr Osborne asked Dr Chlebowski whether he thought that the lack of association between weight gain and breast cancer incidence was due to the fact that women who gained weight were already overweight.

Dr Chlebowski replied that there is "probably a threshold" of weight gain in relation to breast cancer risk and that, after a certain point, another driver of risk "takes over." He added: "We don't have enough evidence about exactly where the threshold is, but I think that's the going hypothesis."

One potential problem that Dr Chlebowski identified in implementing the findings into clinical practice is that there is a general lack of reimbursement, particularly for oncologists, for helping patients lose weight.

"So that's another battle that needs to be conducted," he said.

Dr Osborne added: "What you're saying is that insurance doesn't pay for very much, if anything, for a consultation with a dietician to lose weight, even though it's been known to be a risk factor for many diseases forever."

The study was supported by the National Institutes of Health. Dr Chlebowski is a consultant for Novartis, AstraZeneca, Pfizer, and Genentech. Dr Osborne has financial ties to multiple pharmaceutical companies, including AstraZeneca, Genentech, and Gilead Sciences.

San Antonio Breast Cancer Symposium (SABCS) 2017: Abstract GS5-07. Presented December 8, 2017.

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