[fullofbeans]

Toxicity profile is very low with 3 out of 100,000 developing lactic acidosis after years o use. Seems to also have gastro implication with 10% stopping because of it.

http://jco.ascopubs.org/content/27/20/3271.full.pdf

A less than $10 month treatment with interesting results.

http://abstract.asco.org/AbstView_102_84233.html
Abstract:
Background: Metformin is associated with a reduced incidence of breast cancer and enhanced response to neoadjuvant chemotherapy in epidemiological studies of diabetic women. Cell line and xenograft studies suggest metformin, widely used in the treatment of diabetes, may be a candidate anti-cancer agent. This randomized phase II neoadjuvant trial examined the effects of metformin on Ki67 and gene expression in primary breast cancer, testing the hypothesis that metformin has anti-cancer effects in women with breast cancer. Methods: Non-diabetic women with operable, primary invasive breast cancer received pre-operative metformin. The trial had two components: a pilot cohort of 8 luminal A patients had core biopsy at three time points: at presentation; a week later without treatment (internal control); then following metformin 500mg o.d. for one week increased to 1g b.d. for a further week up to definitive surgery. A further 47 Luminal A and Luminal B patients had core biopsy measurement at diagnosis, were randomized to metformin or no metformin, and 2 weeks later had core biopsy prior to resection. Ki67 measurements and transcriptome analyses were performed on formalin fixed paraffin embedded tissues. Results: The mean percentage of cells staining for Ki67 fell significantly in both the pilot cohort (p=0.041, paired t-test) and patients randomized to metformin (p=0.027, Wilcoxon rank test) following metformin treatment, but was unchanged in the control arm. By Ingenuity Pathway Analysis, the TNFR1 signaling pathway was most significantly affected by metformin: TGFB, MEKK were commonly up regulated and cdc42 down regulated. The mTOR and AMPK pathways were also significantly affected. By Gene Set Analysis the p53, BRCA1 and cell cycle pathways had reduced expressed following metformin. Conclusions: This window of opportunity trial presents evidence of antiproliferative and anti-cancer effects via specific biomarker pathways for metformin action in primary breast cancer and provides support for further trials testing the use of metformin in the treatment of breast cancer.