Weight Loss After Menopause, Lower Breast Cancer Risk

Kristin Jenkins

October 09, 2018

Postmenopausal women who experience a weight loss of ≥5% are at lower risk for invasive breast cancer compared with women whose weight remains stable, say researchers.

Analysis of data from the large, prospective Women's Health Initiative (WHI) Observational Study shows that for postmenopausal women who experienced a weight loss of ≥5% over a 3-year period — whether intentional or not — the risk for breast cancer was 12% lower than that of women whose weight stayed the same.

The study, led by Rowan T. Chlebowski, MD, PhD, of the City of Hope National Medical Center, in Duarte, California, was published online October 8 in Cancer. The study was presented in part at the San Antonio Breast Cancer Symposium on December 8, 2017, and was reported by Medscape Medical News at that time.

"These findings suggest that interventions in postmenopausal women designed to generate weight loss may result in a reduction in breast cancer risk," the authors write.

They note that approximately one third of postmenopausal women in the United States are obese and that obesity is an established risk factor for postmenopausal breast cancer.

Although the analysis did not find an association between a weight gain of ≥5% and increased breast cancer risk (hazard ratio [HR], 1.02), a weight gain of ≥5% was associated with a significant increase in the risk for triple-negative breast cancer (HR, 1.54).

The study's observational design "precludes causal inference," the researchers say. "Because we have no strong biological rationale for the association between weight gain and increasing only triple-negative breast cancer, we now suggest this finding should be interpreted with caution."

Previous Studies

Studies into the impact of weight loss on overall breast cancer risk have produced mixed results, they note, adding that the current findings are supported by evidence from a number of earlier studies and analyses.

In studies of bariatric surgery, for example, a weight loss of >20 kg was associated with a lower breast cancer risk in severely obese women.

"Our current findings suggest benefit for smaller degrees of weight loss achievable without surgery," the authors say.

Results from the current analysis are also supported by evidence from post hoc analyses of follow-up data from the WHI Dietary Modification trial, Chlebowski said in a statement. Those analyses, conducted by Chlebowki's research group, were presented at the San Antonio Breast Cancer Symposium on December 15, 2014, and were reported by Medscape Medical News at that time. They showed that after a mean 16.1-year cumulative follow-up in more than 3000 women diagnosed with incident breast cancer, a 3% weight loss in those who had undergone a low-fat diet was associated with significantly improved overall survival from breast cancer, other cancers, and cardiovascular disease compared to women who followed their usual diet.

"These findings, taken together, provide strong correlative evidence that a modest weight loss program can impact breast cancer," Chlebowski said.

The findings from the current study are not "stand alone," he told Medscape Medical News, pointing to evidence from an earlier analysis of data from the WHI Observational Study. That analysis, also conducted by his research team, showed that moderate weight loss over a 3-year period resulted in a significant reduction in risk for endometrial cancer.

However, a secondary analysis of data from the separate WHI clinical trials population, conducted by another research group, produced somewhat different results. During a median follow-up period of 13 years, there was no association between weight loss or gain and the incidence of breast cancer in women who were already overweight or obese. Notably, an increased risk for breast cancer was shown in women with a baseline body mass index (BMI) of <25.0 who gained more than 5% of body weight.

When asked about these differences, Chlebowski emphasized that "the message is one of moderation." A modest weight loss is something that most postmenopausal women can achieve, he pointed out. "As there was no interaction seen for analyses examining obese vs nonobese women, it is likely that even obese women could benefit as long as they avoided [weight] reduction to BMI 18.5."

"Strong, Unique Evidence"

When approached for comment, Anne McTiernan, MD, PhD, research professor of epidemiology at the Fred Hutchinson Cancer Research Center, in Seattle, Washington, said the current study provides "strong, unique evidence that weight loss after menopause is beneficial for reducing breast cancer risk."

McTiernan is also professor of medicine at the Schools of Medicine and Public Health at the University of Washington. Her own research focuses on diet, obesity, exercise, the risk for cancer development, and cancer prognosis.

It's never too late to reduce your risk of breast cancer. Dr Anne McTiernan

"The bottom line here [is that] it's never too late to reduce your risk of breast cancer," McTiernan told Medscape Medical News.

Unlike previous observational studies that relied on patient-reported changes in weight, the current study measured women's weight at study entry and again 3 years later, she noted. In addition, the study adjusted for other breast cancer risk factors in a large cohort that was followed for more than a decade. It also assessed the type of breast cancer in those who developed disease, McTiernan pointed out.

"In my own clinical studies, we've found that women assigned to a weight loss program with either diet alone or diet plus exercise significantly reduce levels of several blood factors that can promote breast tumor growth, compared to women assigned to a control group that remained weight-stable. These include estrogens, inflammation, insulin, among others," she said.

Study Details

For the current study, the investigators used data from 93,676 US women aged 50 to 79 years who were recruited to the WHI Observational Study between 1993 and 1998. Their final cohort for the analysis was made up of 61,335 postmenopausal women who had no prior breast cancer and whose mammography results were normal.

Local laboratory reports were used to determine estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status. BMI was calculated at baseline and at year 3. Weight change was categorized as stable (<5%), loss (≥5%), or gain (≥5%). Participant self-reports were used to determine whether weight loss was intentional.

At baseline, 41% of women were of normal weight, 34% were overweight, and 25% were obese.

During a mean follow-up of 11.4 years, 3061 incident cases of breast cancer were diagnosed. Compared to 41,139 women whose weight remained stable (a gain of <1 lb), the analysis showed that for 8175 women who lost weight over the 3-year period, the risk for breast cancer was significantly lower (hazard ratio [HR], 0.88; P = .02), with no interaction by BMI. Of these women, 4829 intentionally lost a mean of 19.58 lb, and 3346 experienced an unintentional mean weight loss of 16.90 lb.

Women who experienced a 5% weight gain were more likely to be younger, black, heavier smokers, and younger at the time of their first child's birth compared to women whose weight was stable. Women who experienced intentional weight loss were more likely to have a higher BMI but were less likely to be physically active or to have been prescribed hormone therapy (P < .01) compared to women whose weight did not change.

Most early weight loss was maintained through year 6. The mean time from year 3 weigh-in to the diagnosis of breast cancer was 6.47 years.

In the 12,021 postmenopausal women who gained a mean of 18.5 lb, breast cancer risk was not increased (HR, 1.02). This result was maintained after adjusting for frequeny of mammography. Notably, there were no significant differences in breast cancer risk regardless of whether the weight loss was intentional or unintentional (HR < 1; P = .2 for both).

Larger studies are needed to provide a more definitive understanding about the role of intentional vs unintentional weight loss in cancer risk, the authors say.

McTiernan noted there is strong evidence that women can reduce their risk for postmenopausal breast cancer by maintaining a BMI of <25, staying physically active, eating healthfully, not smoking, drinking little or no alcohol, and undergoing regular mammography screening as recommended.

For patients who need hormone therapy to manage menopausal symptoms, she emphasized that progesterone should either be avoided or its use should be limited to less than 3 years. She also said that the so-called bioidentical hormones and hormonal creams and gels are "no safer than prescription hormones and should be avoided."

Evidence that use of hormones for treatment of postmenopausal symptoms may increase the risk for breast cancer comes from earlier analyses of two separate WHI randomized trials, also led by Chlebowski. These found that the use of combined estrogen and progestin for a mean of 5.6 years significantly increased breast cancer risk (HR, 1.3) and that this elevated risk persisted over 13 years of follow-up.

McTiernan said that for women with a strong family history of breast cancer, a BRCA gene mutation, or a cancer precursor, additional screening with MRI or ultrasound can add valuable information to results from regular mammography screening for early breast cancer detection. Clinicians can also discuss the pros and cons of estrogen-blocking drugs such as tamoxifen (multiple brands), raloxifene (Evista, Eli Lily), and aromatase inhibitors, she suggested.

Prophylactic mastectomy and/or oophorectomy significantly reduces breast cancer risk, McTiernan noted. "Clearly, these options are most appropriate for women at very high risk," she said.

In women at high risk who undergo bilateral mastectomy, risk for breast cancer is reduced by more than 90%, she said. In women who undergo bilateral oophorectomy, breast cancer risk drops by about half compared to women at high risk whose ovaries are intact.

The WHI Observational Study was supported by the National Heart, Lung, and Blood Institute, the National Institutes of Health, and the Department of Health and Human Services. The analysis was supported by the American Institute for Cancer Research. Dr Chlebowski has financial relationships with AstraZeneca, Novartis, and Pfizer. No other significant financial relationships have been reported.

Cancer. Published online October 8, 2018. Abstract


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