Obesity is associated with worse outcomes in patients with ER-positive/HER2-negative disease

Obesity was associated with worse overall and disease-free survival in women with operable breast cancer treated with adjuvant chemotherapy, but for the first time, researchers observed this finding in only a specific subset of patients - those with estrogen receptor (ER)-positive/HER2-negative disease.

About one third of all adults in the United States are obese, posing a major public health problem because of obesity's association with an increased risk of diabetes and heart disease. This study indentified a new hazard associated with obesity.

Results were presented at the 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium, held Dec. 8-12, 2010.

"We were surprised to find that there was no evidence that this finding played out in the other breast cancer subtypes - it's mainly a phenomenon that we seem to be seeing those with ER-positive/HER2-negative disease," said Joseph A. Sparano, M.D., professor of medicine and women's health at Albert Einstein Medical College of Medicine and associate chairman of the department of oncology at Montefiore Medical Center in Bronx, N.Y.

"Our results may be explained by the fact that obesity is associated with hyperinsulinemia, which may drive the growth of estrogen-dependent tumors," said Sparano.

Sparano and colleagues conducted a retrospective study to evaluate the effect of obesity on the outcomes of three Eastern Cooperative Oncology Group trials: E1199, E5188 and E3189. All three trials involved doxorubicin/cyclophosphamide and other agents.

The researchers first evaluated the relationship between body mass index (BMI) and disease-free survival and overall survival in the E1199 trial. Results showed a nonsignificant trend toward worse disease-free survival and overall survival for the obese patients compared with others.

However, after evaluating these data by breast cancer subtype, obese women with ER and/or progesterone receptor (PR)-positive/HER2-negative disease had significantly worse disease-free survival and overall survival. The same effect was not seen in women with HER2-positive and triple-negative disease.

After this initial finding was seen in the E1199 trial, the research team attempted to validate these findings in two other trials, one of which included only ER-positive disease (E5188) and a second that included only ER-negative disease. The results held up in these two other studies - obesity was associated with worse outcomes in patients with ER-positive disease in the E5188 trial, but only in patients with ER-negative disease treated in the E3189 trial.

"If validated in other studies, this finding provides strong rationale for trying to identify potential causes, and prospectively evaluate intervention strategies designed to reduce their risk of recurrence," Sparano said.

The researchers plan additional studies to evaluate the relationship between obesity and tumor gene expression, and to identify other host factors that may be associated with recurrence, such as insulin and other growth-factor levels.