Metformin Increases Pathologic Complete Response Rates in Breast Cancer Patients With Diabetes

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Title: Metformin Increases Pathologic Complete Response Rates in Breast Cancer Patients With Diabetes
URL: http://www.pslgroup.com/dg/222E46.htm
Doctor's Guide
June 3, 2008

CHICAGO -- June 3, 2008 -- Metformin, the common first-line drug for type 2 diabetes, may be effective in increasing pathologic complete response rates in women with diabetes and early-stage breast cancer who took the drug during chemotherapy prior to having surgery. This study will pave the way for further research of the drug as a potential cancer therapy, according to researchers at the University of Texas M. D. Anderson Cancer Center, Houston, Texas.

The retrospective study is the first clinical research observation of the diabetes drug as a potential antitumour agent. The findings will be presented at the American Society of Clinical Oncology (ASCO) 44th Annual Meeting in a poster discussion session by Sao Jiralerspong, MD, PhD, and Ana M. Gonzalez-Angulo, MD, both in M. D. Anderson's Department of Breast Medical Oncology.

"Metformin has a novel mechanism of action. There have been a number of papers published recently that describe its action through activation of the AMP kinase pathway, which is a cellular energy sensor of the cells and potentially important pathway for the development of cancer," said Dr. Jiralerspong.

"The other interesting aspect is that metformin works by decreasing the amount of insulin resistance in [patients with diabetes] and insulin seems to be a growth factor for cancer," said Dr. Gonzalez-Angulo.

Using the M. D. Anderson Breast Medical Oncology database, Dr. Gonzalez-Angulo, Dr. Jiralerspong, and their team identified 2,529 women with early-stage breast cancer who received chemotherapy in the neoadjuvant setting, before surgery. Of the patients, 2,374 did not have diabetes, 68 did have diabetes but were not taking metformin, and 87 had diabetes and were taking metformin. The study's endpoint was pathologic complete response or the absence of cancer at the time of surgery.

The researchers found that the pathologic complete response rates in the breast cancer patients with diabetes taking metformin was 24%, 3 times higher than the rates in patients with diabetes not taking the drug. In the women without diabetes, the pathologic complete response rate was 16%. After adjusting for other factors, the researchers found that metformin was an independent predictor of pathologic complete response in patients with diabetes.

While very exciting, the findings are still very early, cautioned Dr. Jiralerspong and Dr. Gonzalez-Angulo, and further investigation with metformin is needed.

"We need to study the mechanism of the drug. Perhaps it's the decrease in insulin levels, or it may be that the drug has an antitumour effect that we to look at in vivo," said Dr. Gonzalez-Angulo. "Our next step is to conduct a number correlative studies to try and further understand its mechanism."

SOURCE: University of Texas M. D. Anderson Cancer Center

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