Metformin and Pathologic Complete Responses to Neoadjuvant Chemotherapy in Diabetic Patients With Breast Cancer

• Published in: Journal of clinical oncology Vol. 27; no. 20; pp. 3297 - 3302
• Main Authors: JIRALERSPONG, Sao, PALLA, Shana L, GIORDANO, Sharon H, MERIC-BERNSTAM, Funda, LIEDTKE, Cornelia, BARNETT, Chad M, HSU, Limin, HUNG, Mien-Chie, HORTOBAGYI, Gabriel N, GONZALEZ-ANGULO, Ana M
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 10-07-2009
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Diabetes Mellitus - drug therapy; Diabetes Mellitus - pathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Humans; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - therapeutic use; Logistic Models; Medical sciences; Metformin - administration & dosage; Metformin - therapeutic use; Middle Aged; Multivariate Analysis; Neoadjuvant Therapy; Original Reports; Remission Induction; Survival Analysis; Treatment Outcome; Tumors; Endocrinopathy; Human; Breast disease; Diabetes mellitus; Breast cancer; Malignant tumor; Neoadjuvant treatment; Mammary gland diseases; Chemotherapy; Biguanides; Treatment; Cancerology; Metformin; Cancer
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2009.19.6410

Population studies have suggested that metformin use in diabetic patients decreases cancer incidence and mortality. Metformin inhibits the growth of cancer cells in vitro and tumors in vivo. However, there is little clinical data to support this. Our purpose was to determine whether metformin use was associated with a change in pathologic complete response (pCR) rates in diabetic patients with breast cancer receiving neoadjuvant chemotherapy.
We identified 2,529 patients who received neoadjuvant chemotherapy for early-stage breast cancer between 1990 and 2007. Patients were compared by groups: 68 diabetic patients taking metformin, 87 diabetic patients not taking metformin, and 2,374 nondiabetic patients. pCR rates were compared between the three groups using chi(2) tests of independence and compared pair- wise using a binomial test of proportions. Factors predictive of pCR were assessed using a multivariate logistic regression model.
The rate of pCR was 24% in the metformin group, 8.0% in the nonmetformin group, and 16% in the nondiabetic group (P = .02). Pairwise comparisons between the metformin and nonmetformin groups (P = .007) and the nonmetformin and nondiabetic groups (P = .04) were significant. Comparison of the pCR rates between the metformin and nondiabetic groups trended toward but did not meet significance (P = .10). Metformin use was independently predictive of pCR (odds ratio, 2.95; P = .04) after adjustment for diabetes, body mass index, age, stage, grade, receptor status, and neoadjuvant taxane use.
Diabetic patients with breast cancer receiving metformin and neoadjuvant chemotherapy have a higher pCR rate than do diabetics not receiving metformin. Additional studies to evaluate the potential of metformin as an antitumor agent are warranted.