REPORTING FROM SABCS 2017

SAN ANTONIO (FRONTLINE MEDICAL NEWS) – Postmenopausal women may be able to lower their risk of invasive breast cancer by simply losing some weight, according to an analysis of the large prospective Women’s Health Initiative Observational Study.

“While obesity is an established risk factor for postmenopausal breast cancer, studies of weight loss and breast cancer provide inconsistent results. It’s been very, very difficult to show that losing weight changes breast cancer incidence,” said lead investigator Rowan T. Chlebowski, MD, PhD, research professor in the department of medical oncology and therapeutics research at City of Hope in Duarte, Calif. “Consequently, the current public health message is limited to ‘avoid body fatness’ [N Engl J Med. 2016;375:794-8]. That’s not a very strong public health message.”

He and his coinvestigators assessed changes in study participants’ weight during the first 3 years and then ascertained their invasive breast cancer risk after a median follow-up of 11.4 years.

Results showed that compared with peers whose weight remained stable, women who lost at least 5% of their body weight (an average of about 17-20 pounds) had a significant 12% reduction in breast cancer risk, Dr. Chlebowski reported in a session and press briefing at the San Antonio Breast Cancer Symposium. Benefit was similar whether the weight loss was intentional or not, and whether women were normal weight, overweight, or obese at baseline.

“These findings suggest that interventions in postmenopausal women designed to generate weight loss may reduce breast cancer risk. I feel these are very optimistic findings in that they provide a lesson to postmenopausal women that even a moderate degree of weight loss may be associated with health benefits,” he said. “This is a relatively new finding, and I think it should have public health implications.”

Parsing the findings

“I hope that you can present this to general doctors rather than oncologists because those are the ones seeing healthy women, by and large,” said press briefing moderator C. Kent Osborne, MD, codirector of SABCS and director of the Dan L. Duncan Cancer Center at Baylor College of Medicine in Houston. “But in my patients, I’ve always suggested that they lose weight. Most of them with breast cancer are overweight, it seems. And I always had to do it because of diabetes and other factors. Now we can do it because we have a breast cancer endpoint that also suggests that losing weight will help with that as well.”

In discussions among the investigators about implementing the study’s findings via weight loss counseling and intervention, reimbursement was identified as an ongoing concern, Dr. Chlebowski noted. “Certainly, oncologists do not get any money for encouraging this or taking any steps to implement this. So that’s another battle that needs to be conducted.”

Additional results from the study showed that women who experienced a weight gain of at least 5% did not have a significantly elevated risk of breast cancer overall.

“Do you think that the women who gained a little bit of weight didn’t have an increase in incidence because they were already overweight?” Dr. Osborne asked.

“When we go over all these very complex mechanisms and the different drivers, there’s probably a threshold. So obesity’s association with inflammatory factors, I think that’s a driver to a certain degree. But then something else takes over, or maybe the main driver takes over,” Dr. Chlebowski replied. “We don’t have enough data to decide exactly what that threshold is, but that’s the ongoing hypothesis.”

In the session, attendee Daniel McGrail, PhD, of the MD Anderson Cancer Center, Houston, asked, “Since this [risk reduction with weight loss] occurred regardless of initial [body mass index], and you have all these covariates accounted for, does that imply that actually caloric deficits or decreasing caloric intake could be preventing breast cancer risk regardless of initial weight or any other parameters?”

“In all these western diseases, what we take for normal is probably less normal than it might have been 250 years ago or thousands of years ago when we were eating berries and being chased by animals,” Dr. Chlebowski replied. “So this raises a question as to whether the normal weight cutoff should be an ideal weight for western cancer prevention.”

Study details

The Women’s Health Initiative Observational Study recruited 93,676 postmenopausal women aged 50-79 years from 40 U.S. clinical centers during 1993-1998. The women had measurements taken of height and weight at baseline and at year 3 for calculation of BMI, and were asked about intentionality of any weight loss during that period.

Analyses were based on 61,335 women who had normal or higher body weight and were cancer free at baseline, survived at least 3 years, and had adequate data.

Overall, about 13.3% of women lost at least 5% of their body weight between baseline and year 3; 7.9% did so intentionally, losing an average of 19.6 pounds, and 5.5% did so unintentionally, losing an average of 16.9 pounds.

“We used the 5% decrease because this level has been shown to change some biochemical markers potentially associated with cancer. And it has been shown in a different study population, a randomized trial, to reduce the frequency of diabetes,” Dr. Chlebowski noted.

“There was nothing that the study did to induce the weight loss. And based on a partial look at the data, it doesn’t look like many of the women went to some kind of program to lose weight. So it was probably self-directed weight loss,” he noted. “Interestingly, the body mass index of this group was 29.9, so they were on the verge of going into obesity. We wondered in retrospect whether that was a motivating factor for them.”

In multivariate analysis, relative to peers having a stable weight over time, the women losing at least 5% of their weight had a lower risk of breast cancer (hazard ratio, 0.88; 95% confidence interval, 0.78-0.98; P = .02).

Findings were unchanged after further adjustment for mammography frequency. In addition, risk reduction was statistically indistinguishable whether the weight loss was intentional or not (P = .2 for interaction), and whether women were normal weight, overweight, or obese at baseline (P = .4 for interaction).

The 19.6% of women who had a weight gain of at least 5% did not have a significantly elevated risk of breast cancer overall, but they did have a significantly elevated risk of triple-negative breast cancer (HR, 1.54; 95% CI, 1.16-2.05). “We really don’t have a good explanation for this,” Dr. Chlebowski said.

Tackling the global obesity epidemic by conventional means to reduce cancer risk is an uphill battle, he concluded. “We are going to be looking for possible mediating factors. If you can find the mediating factors, pharmacologic intervention would have a much greater chance of success.”

Dr. Chlebowski disclosed that he had no relevant conflicts of interest. Research was supported by the National Heart, Lung and Blood Institute; National Institutes of Health; Department of Health and Human Services; and American Institute for Cancer Research.

op@frontlinemedcom.com

SOURCE: Chlebowski et al., SABCS 2017 Abstract GS5-07

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