SABCS 2010: Obesity Ups Risk of Recurrence for Some Women With HER2-Negative Breast Cancer

Being obese at the time operable breast cancer is diagnosed is associated with inferior outcomes in women with estrogen receptor (ER)— or progesterone receptor (PR)–positive, HER2-negative breast cancer. This breast cancer subtype is typically associated with a more favorable prognosis than most other subtypes. “Not only did this group of obese patients diagnosed with breast cancer have a higher risk of recurrence; if they did recur, they had a higher risk of death,” said lead author Joseph Sparano, MD, professor of Medicine and Women’s Health at Albert Einstein College of Medicine and associate chairman of the Department of Oncology at Montefi ore Medical Center, Bronx, New York.

For this retrospective study, investigators from several North American breast cancer groups worked in collaboration, analyzing data for the thousands of women enrolled in trials conducted by the Eastern Cooperative Oncology Group, including E1199, E5188, and E3189.

Obesity was defined as having a body mass index (BMI) >30 kg/m². BMI data was available for 75% of patients enrolled in E1199 (N = 3484). Of these, 2115 had ER- and/or PR-positive and HER2-negative breast cancer; 38% were obese. Doxorubicin and cyclophosphamide were among the prior treatments the women had received. Disease characteristics, such as median tumor size, nodal status, ER/PR or HER2 expression levels, and type of endocrine therapy, did not differ between obese and nonobese patients.

Investigators identified an association between obesity and older age, however: 76% of patients aged ≥45 years were obese compared with 67% of women aged <45 years. Women who were postmenopausal were more likely than women who were premenopausal to be obese (58% vs 50%, respectively), and black women were more likely than women of other races to be obese (14% vs 6%, respectively). Sparano said more of the women who had breast conservation surgery were obese than women who did not (43% vs 39%, respectively).

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A multivariate analysis, adjusted for covariates, found no signifi cant decrease in disease-free survival or overall survival (OS) for obese women overall or for the subset of women who had HER2-positive or triple-negative disease. Those women with hormone receptor—positive, HER2-negative disease had a 23% increased risk of recurrence (hazard ratio [HR], 1.24; = .026) and a 46% increased mortality risk (HR, 1.42; = .003), however.

Sparano said women with ER- and PR-positive/HER2-negative breast cancer account for 50% of all breast cancer cases in the United States. “We only saw the [negative] effect of obesity in this group.”

The investigators looked at BMI at diagnosis as a continuous variable; they found a positive correlation between recurrence rate and BMI. The correlation between increasing BMI and worse OS was even stronger, Sparano said.

Sparano and colleagues also analyzed the effect of obesity at baseline on outcomes in E5188 (N = 1501) and E3189 (N = 610). Those trials involved treatment with doxorubicin or cyclophosphamide and other agents. They found an association between obesity at baseline and worse outcomes for women with hormone receptor—positive disease in these trials, as well.

“We would like to conduct additional trials to monitor weight prospectively and also monitor other baseline factors that could be associated with outcomes,” said Sparano.

At the press conference where Sparano presented the data, moderator Judith Garber, MD, Dana-Farber Cancer Institute, Boston, Massachusetts, emphasized that this study only considered the effect of baseline obesity on outcomes. “Women with breast cancer gain weight over time, and some treatments might increase weight gain. This is worrisome,” she said.

About one-third of all adults in the United States are obese. In the past 3 decades, obesity has doubled in adults and tripled in children. Obesity increases the risk of many health problems, including cancer, diabetes, and heart disease, and is consequently associated with a higher mortality risk. The new findings are of particular concern because this group of women with hormone receptor—positive, HER2- negative disease would typically have a good prognosis if they were not obese at diagnosis, explained Sparano. ABSTRACT S2-1