Authors: Nananda F Col Leslie Ochs Vicky Springmann Aaron K Aragaki Rowan T Chlebowski
Publish Date: 2012/07/31
Volume: 135, Issue: 3, Pages: 639-646
Abstract
Observational studies have suggested that metformin decreases the incidence of several common cancers However findings regarding breast cancer have been mixed In order to explore this issue a systematic literature review and metaanalysis were performed with a focus on potential biases We conducted a comprehensive literature search for all pertinent studies addressing metformin use and breast cancer risk by searching PubMed Cochrane Library and Scopus which includes Embase ISI Web of Science using the Mesh terms “metformin” or “biguanides” or “diabetes mellitus type 2/therapy” and “cancer” or “neoplasms” When multiple hazard ratios HR or odds ratio OR were reported the most adjusted estimate was used in the basecase analysis We pooled the adjusted HR and performed sensitivity analyses on duration of metformin use or ≤3 years use study quality assessed using the GRADE system and initial observation year of the cohort before vs after 1997 From a total of 443 citations 18 fulltext articles were considered and seven independent studies were included All were observational four cohort and three case control Our combined OR of all seven studies was 083 071–097 Stronger associations were found when analyses were limited to studies estimating the impact of longer metformin use OR = 075 95 CI 062 091 or among studies that began observing their cohort before 1997 OR = 068 95 CI 055–0084 Stratification according to study quality did not affect the combined OR but higher quality studies had smaller CI and achieved statistical significance Interpretation is limited by the observational nature of reports and different comparison groups Our analyses support a protective effect of metformin on breast cancer risk among postmenopausal women with diabetes Clinical trials are needed for definitive determination of the role of metformin in breast cancer risk reduction
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