(23-12-10) Obesity Linked to Risk for Metastasis and Death in Breast Cancer

Roxanne Nelson


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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.


Source: J Clin Oncol. Published online November 29, 2010.

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