Antidiabetic Agent Metformin May Boost pCRs in Breast Ca

CHICAGO-The insulin sensitizer metformin may increase the response to neoadjuvant chemotherapy in diabetic patients with breast cancer, according to a retrospective study presented at ASCO 2008 (abstract 528).

In the first study to evaluate metformin as an anti-tumor agent, diabetic patients on metformin had a threefold increased rate of pathologic complete response (pCR), compared with diabetic patients not receiving metformin, and a 50% higher response rate, compared with nondiabetic patients, reported Sao Jiralerspong, MD, PhD, a fellow at The University of Texas M.D. Anderson Cancer Center.

The study was based on epidemiologic findings that pointed to a protective effect of metformin against cancer.

"Metformin has a novel mechanism of action. It activates the AMP kinase pathway, which is a cellular energy sensor within the cells and may be important in the development of cancer," Dr. Jiralerspong explained.

It also decreases the amount of insulin resistance, and insulin appears to be a growth factor for cancer, he added.

In the M.D. Anderson database, the team identified 2,529 women with early-stage breast cancer who received neoadjuvant chemotherapy. They found the pCR rates to be 24% in diabetic patients taking metformin (n = 68) vs 8% in diabetics not on the drug (n = 87). In nondiabetics, pCRs were observed in 16%.

P values were .02 overall, .007 vs diabetic patients without metformin, and .099 vs nondiabetic patients.

In a multivariate analysis, metformin was an independent predictor of pCR in diabetic patients.

With a median follow-up of 37 months, recurrence-free survival was not significantly different among the three study groups.

The nondiabetic patients, however, had significantly better overall survival (86%) than the diabetic patients on metformin (81%) and the diabetic patients not on metformin (78%).

‘It does appear to have an effect'

Jenny Chee Ning Chang, MD, of Baylor College of Medicine, Houston, suggested in the poster discussion session that metformin probably inhibits the growth of breast cancer cells and, by extension, should increase pCR rates.

"In a study of more than 2,000 patients, it almost tripled the pCR rate. Therefore, it does appear to have an effect" in the neoadjuvant setting, Dr. Chang said.