CHICAGO — The widely used diabetes drug metformin may have an antitumor effect, according to data from a retrospective study of more than 2,500 breast cancer patients, including 155 women with diabetes.
Patients taking metformin for diabetes had a threefold higher pathologic complete response (pCR) rate after neoadjuvant chemotherapy, compared with those who had diabetes but were not on metformin (24% vs. 8%, P = .007), Dr. Sao Jiralerspong of the University of Texas M.D. Anderson Cancer Center in Houston reported in a poster at the annual meeting of the American Society of Clinical Oncology.
The rate of pCR, defined as no residual disease in the breast or lymph nodes, also was higher in the cohort of patients taking metformin than in patients without diabetes, who had a pCR rate of 16% after neoadjuvant chemotherapy (P = .099).
Recent epidemiologic studies suggest that metformin may reduce the incidence of cancer and cancer-related mortality in diabetic patients. The drug activates adenosine monophsphate-activated protein (AMP) kinase, inhibits the mammalian target of rapamycin (mTOR) pathway, and has been shown to inhibit the growth of breast cancer cell lines in pre-clinical studies, said Dr. Jiralerspong.
To explore the possibility that metformin's antiproliferative effects might increase the efficacy of neoadjuvant chemotherapy in diabetic breast cancer patients, Dr. Jiralerspong and his colleagues reviewed the charts in the M.D. Anderson Breast Medical oncology database of 2,529 patients who received neoadjuvant systemic therapy for early stage breast cancer.
Ninety-four percent of patients (2,374) did not have diabetes; 68 patients had diabetes and were treated with metformin, and 87 patients had diabetes but were not treated with metformin. The median age of the full study population was 49 years (range 21–87 years), most of the tumors were hormone receptor-positive, and 25% were HER2-positive. Baseline characteristics of patients with and without diabetes were similar, although the diabetic groups tended to be slightly older and more obese, Dr. Jiralerspong noted.
Metformin use was independently predictive of pCR (odds ratio 3.2, P = .023) after adjustment for diabetes, body mass index, age, stage, grade, estrogen receptor (ER)/progesterone receptor (PR) status, and neoadjuvant taxane use.
After a median follow-up of 39 months, the recurrence-free survival was similar in the three groups. Overall survival was significantly better, however, in the nondiabetic cohort (86%), compared with 81% for the diabetic patients on metformin and 78% for the diabetic patients not on metformin (P = .02).
“This could just be due to short follow-up, and also there may be other factors at play. Diabetics probably are going to do worse in general, and we are starting to look at the causes of death now because it might have been noncancer causes of death that produced these results,” Dr. Jiralerspong said.
He emphasized that this retrospective analysis was hypothesis generating, but said that the results warrant prospective studies to more fully evaluate the potential of metformin as an antitumor agent.
Dr. Jiralerspong said he had no conflicts of interest to declare.