Long-Term Metformin Use Is Associated With Decreased Risk of Breast Cancer

Abstract

OBJECTIVETo evaluate whether use of oral hypoglycemic agents is associated with an altered breast cancer risk in women.RESEARCH DESIGN AND METHODSUsing the U.K.-based General Practice Research Database, we conducted a nested case-control analysis among 22,621 female users of oral antidiabetes drugs with type 2 diabetes. We evaluated whether they had an altered risk of breast cancer in relation to use of various types of oral hypoglycemic agents. Case and control patients with a recorded diagnosis of type 2 diabetes were matched on age, calendar time, and general practice, and the multivariate conditional logistic regression analyses were further adjusted for use of oral antidiabetes drugs, insulin, estrogens, smoking BMI, diabetes duration, and HbA1c (A1C).RESULTSWe identified 305 case patients with a recorded incident diagnosis of breast cancer. The mean ± SD age was 67.5 ± 10.5 years at the time of the cancer diagnosis. Long-term use of ≥40 prescriptions (>5 years) of metformin, based on 17 exposed case patients and 120 exposed control patients, was associated with an adjusted odds ratio of 0.44 (95% CI 0.24–0.82) for developing breast cancer compared with no use of metformin. Neither short-term metformin use nor use of sulfonylureas or other antidiabetes drugs was associated with a materially altered risk for breast cancer.CONCLUSIONSA decreased risk of breast cancer was observed in female patients with type 2 diabetes using metformin on a long-term basis.

Metformin and Cancer Risk in Diabetic Patients: A Systematic Review and Meta-analysis

“…When analysis was done separately by cancer incidence and cancer mortality, we found similar SRRs with a decrease in heterogeneity for mortality and no statistically significant difference (P = 0.90) between the two estimates. When the six studies on incidence of single cancer sites, that is, colon (40), pancreatic (38), HCC (34,45), breast (46), and prostate (39) cancers, were included, similar summary risk estimates were obtained (SRR, 0.55; 95% CI, 0.42-0.70). A trend toward a large risk reduction was noted for colon and pancreatic cancer (60-80% risk reduction) in two independent studies for each cancer site, even when only those cancers diagnosed >2 years after diabetes developed were included (to minimize effects of reverse causation).…”

“…Eight of these articles were not included in the meta-analysis for the following reasons: (a) two referred to the same study cohort: Evans et al (35) presented a subset of patients included in a study published later (36), and Jecht (37) published in a German language journal the results already presented in English by Libby et al (36); (b) six did not report overall cancer incidence but data on a single organ site, that is, pancreatic cancer (38), hepatocellular cancer (HCC; refs. 34,45), breast (46), prostate (39), and colorectal cancer (40). These studies were analyzed separately for descriptive purposes.…”

“…Metformin has been associated with cancer risk reduction in recent epidemiologic studies in diabetic patients (34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46). With these premises, we performed a systematic review and meta-analysis of available studies to better define the effect of metformin on cancer incidence and mortality in diabetic patients.…”

Development and validation of fast and simple flow injection analysis–tandem mass spectrometry (FIA–MS/MS) for the determination of metformin in dog serum

“…Of recent interest is the potential repurposing of metformin, an oral insulinsensitizer used as first-line treatment for Type 2 diabetes (DM2). Specifically, there is now interest in validating the several meta-analyses indicating the usefulness of metformin in cancer therapy and/or prevention [1][2][3]. Indeed, cytotoxic effects of metformin in many cancer cell lines has been demonstrated [4,5].…”

Diet and tumor LKB1 expression interact to determine sensitivity to anti-neoplastic effects of metformin in vivo

“…This research is motivated in part by hypothesis-generating epidemiological studies, which suggest that diabetic patients receiving metformin have substantially (B40%) reduced cancer burden compared with diabetic patients receiving other therapies (Evans et al, 2005;Currie et al, 2009;Libby et al, 2009;Bodmer et al, 2010;Landman et al, 2010).…”