Obesity Linked to Risk for Metastasis and Death in Breast Cancer

Roxanne Nelson

December 17, 2010

December 17, 2010 — A new study lends further evidence to what has already been suspected: obesity can affect outcomes in breast cancer. In a large, retrospective analysis, Danish researchers found that obesity is an independent prognostic factor for mortality and developing distant metastases after a diagnosis of breast cancer.

In addition, adjuvant therapy appeared to be less effective, on a long-term basis, among obese patients with breast cancer.

Published online November 29 in the Journal of Clinical Oncology, the results showed that after adjusting for disease characteristics, the risk of developing distant metastases after 10 years was significantly increased (by 46%) in patients with a body mass index (BMI) of 30 kg/m2. The risk of dying from breast cancer after 30 years was also significantly increased (by 38%).

"It has become increasingly clear that obesity is associated with increased cancer risk and mortality, and that obesity has the potential to diminish important advances that have been made in the fight against breast and other cancers," according to an accompanying editorial.

Thus, these data have important implications for cancer prevention and treatment, write Frank A. Sinicrope, MD, from the Mayo Clinic in Rochester, Minnesota, and Andrew J. Dannenberg, MD, from Weill Cornell Cancer Center in New York City. They point out that both endocrine and metabolic changes that are associated with obesity are reversible by weight reduction.

Losing at least 10% of body weight has been shown to reduce serum concentrations of estradiol, leptin, and insulin, and losing weight also increases concentrations of sex hormone–binding globulin and adiponectin, they note. In addition, weight reduction in obese individuals leads to a reduction in levels of proinflammatory cytokines.

"Therefore, changes in diet and increased physical activity to achieve a healthier body weight are a cancer-prevention strategy that may also improve the prognosis of patients with curatively resected breast and other cancers," the editorialists write. In addition, as the current study shows that obesity may reduce the efficacy of endocrine therapy, it is possible that weight loss will increase the efficacy of these agents, even in the adjuvant setting.

Add Evidence to Existing Data

The current study adds to the existing evidence that obesity is associated with poor outcomes in breast cancer, Dr. Sinicrope and Dr. Dannenberg conclude. "Accordingly, obese patients with breast cancer should be made aware of the substantial evidence for the adverse impact of obesity on risk and outcome, and should be counseled about the potential importance of lifestyle changes to improve weight control."

As previously reported by Medscape Medical News, factors such as maintaining a healthy weight and getting regular physical exercise may reduce a woman's risk for breast cancer. In addition, obesity, along with alcohol use and smoking, can significantly increase the risk for second primary invasive contralateral breast cancer among breast cancer survivors.

High BMI Increases Risk for Metastasis and Death

In the current study, Marianne Ewertz, MD, DMSc, from the Department of Oncology, Odense University Hospital in Denmark, and colleagues, used the Danish Breast Cancer Cooperative Group to identify 53,816 women treated for early-stage breast cancer in Denmark between 1977 and 2006. These patients all had complete follow-up information for first events (locoregional recurrences and distant metastases) up to 10 years, and mortality data up to 30 years.

Within this group, information on BMI at diagnosis was available for 18,967 (35%) patients. The cohort was divided into 4 categories, according to BMI: less than 25 kg/m2, 25 to 29 kg/m2, 30+ kg/m2, and unknown.

Patients with a BMI of 30 kg/m2 or greater tended to be older, were more often postmenopausal, had larger tumors, and had both more lymph nodes removed and more positive lymph nodes, but had less invasion into deep fascia (P < .001 for all), compared with those with a BMI of less than 25 kg/m2.

At a median estimated potential follow-up period of 7.1 years, there were 4180 locoregional recurrences and 7278 distant metastases as first events. Although BMI did not seem to influence the risk for locoregional recurrences, risk for distant metastases rose with increasing BMI. At 10 years, the cumulative incidences were

  • 20.1% (95% confidence interval [CI], 19.2% - 20. 9%) for patients with a BMI of less than 25 kg/m2,

  • 22.4% (95% CI, 21.1% - 23.8%) for patients with a BMI of 25 to 29 kg/m2, and

  • 24.3% (95% CI, 22.1% - 26.5%) for patients with a BMI of 30 kg/m2 or more.

The authors noted that among the group of patients whose BMI was unknown, the risk of developing distant metastases throughout the 10 years of follow-up was consistently lower: At 10 years, the cumulative incidence was 16.1% (95% CI, 15.6% - 16.6%).

At a median estimated potential follow-up of 11.4 years, 15,197 patients had died of breast cancer, and 5967 had succumbed to other causes. There was a trend of increasing risk for breast cancer–specific mortality with increasing BMI. At 30 years, the cumulative risks of dying from breast cancer were

  • 46.4% (95% CI, 44.8% - 48.0%) for patients with a BMI of less than 25 kg/m2,

  • 53.4% (95% CI, 50.5% - 56.2%) for patients with a BMI of 25 to 29 kg/m2, and

  • 57.2% (95% CI, 51.8% - 62.2%) for patients with a BMI of 30 kg/m2 or more.

Those with unknown BMI had a consistently lower risk of dying from breast cancer; the cumulative risk at 30 years was 41.1% (95% CI, 40.2% - 42.0%). The risk for death from other causes was also higher among patients with the greatest BMI compared with those in the other weight categories.

The authors also evaluated the efficacy of adjuvant treatment in lean and obese women. Although they did not observe a specific pattern during the first 10 years of follow-up, both chemotherapy and endocrine therapy seemed to be less effective in patients with BMIs of 30 kg/m2 or greater after 10 or more years.

The authors have disclosed no relevant financial relationships.

J Clin Oncol. Published online November 29, 2010.

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