Diabetes, metformin and breast cancer: a tangled web
Menée à l'aide de données 2003-2009 de la cohorte "Sister Study" portant sur 44 541 personnes (âge : 35-74 ans ; durée médiane de suivi : 8,6 ans), cette étude analyse l'association entre un diabète de type 2, une utilisation de metformine et le risque de cancer du sein (2 678 cas), en fonction du statut des récepteurs hormonaux
Résumé en anglais
In the midst of an epidemic of obesity and type 2 diabetes (T2D), the association of diabetes and its treatment with breast cancer (BC) risk has been receiving increasing attention. This association is biologically plausible, given the numerous metabolic perturbations seen in T2D (e.g. hyperinsulinemia, dysglycemia, dyslipidemia, inflammation) that may impact cancer. Indeed, two meta-analyses have identified a modest but statistically significant association of T2D with overall BC risk [summary risk ratio (RR) 1.20; 95% confidence interval (CI), 1.12-1.28 and 1.27; 95% CI, 1.16-1.39, respectively]. Metformin, commonly used as first-line treatment of T2D, may lower BC risk either indirectly by reducing circulating insulin levels, leading to reduced signaling through PI3K and ras pathways, or directly through action on Complex I in the mitochondrium leading to an LKB1-mediated activation of AMPK with downstream inhibition of mTOR. Metformin may also impact rag GTPases, cancer stem cells and tumor microenvironment and may have its greatest anti-cancer effect in triple negative BC (TNBC). Although early epidemiologic studies suggested metformin was associated with reduced BC risk, more recent studies have not identified statistically significant reductions in risk. Nonetheless, given metformin mechanisms of action, it is possible that metformin treatment ameliorates associations of T2D with BC.
