The recently reported population-based case–control study (1) of long-term (≥10 years) statin use among postmenopausal woman showing a two-fold risk of developing both invasive ductal and lobular breast carcinoma compared with never users of statins is disconcerting, although it is only hypothesis generating. However, as statins are increasingly and widely used for cardiovascular disease prevention at higher doses for long periods of time, the implications of the study question the wisdom of certain prescribing patterns. Moreover, recent statin trials elucidate plausible biologic mechanisms of how long-term statin therapy might lead to increased cancer risk.

Many randomized trials have shown that statin therapy can lead to new onset of diabetes (2). Interestingly, certain groups of patients are at particular increased risk for statin induced diabetes; they include women (2, 3), Asians, and the elderly (2). Long-term observational data have indicated that diabetes is positively and significantly associated with all-cause and cancer mortality in women and men, including breast cancer in both women and men (4). Furthermore, statin therapy has been associated with an increase in fasting blood insulin levels (2), and chronic hyperinsulinemia can lead to increased expression of insulin-like growth factor-1 which has mitogenic effects (5).

Therefore, postmenopausal women prescribed long-term statin therapy might be at increased risk of ductal and lobular breast cancer resulting from the off-target diabetogenic and hyperinsulinemic effects of these drugs. Finally, the risk–benefit ratio of long-term statin therapy might be justified in the secondary prevention of cardiovascular disease in postmenopausal women, but long-term statin therapy in the primary prevention of cardiovascular disease in this particular group is unproven, potentially harmful, and warrants further investigation.

No potential conflicts of interest were disclosed.

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