Effects of statin use on volumetric mammographic density: results from the KARMA study

Background: Epidemiological data on statins and breast cancer risk have been inconclusive. The aim of this study was to clarify the role of statins in breast cancer risk by studying their effect on mammographic density. Methods: The KARolinska MAmmography project for risk prediction of breast cancer (KARMA) includes 70,877 women who underwent either a screening or clinical mammography from January 2011 to December 2013. In total, 41,102 women responded to a web-based questionnaire, and had raw digital mammograms stored. Volumetric mammographic density was measured using Volpara(TM) and information on statin use was obtained through linkage with the Swedish National Prescription Register. Analysis of covariance was used to study the effect of statin use on mammographic density, adjusting for a large set of potential confounders. We also studied the effects of statin class and treatment duration and tested for potential effect modification by hormone replacement therapy (HRT). Results: Statin use was recorded in 3,337 women (8.1 %) of the study population and lipophilic statins was the most commonly prescribed type (93.4 % of all statin users). After multivariable adjustment, percent dense volume was lower in statin users than in non-users (P < 0.001). This association was explained by a larger absolute non-dense volume in statin users (P < 0.001). Overall, no difference in absolute dense volume was detected, but interaction analyses revealed a larger dense volume among statin users who reported ever HRT use (P = 0.03). No differential effects were observed according to statin lipophilicity and treatment duration. Conclusions: We observed no overall effect of statin use on mammographic density in terms of absolute dense volume, although a larger absolute dense volume was observed in statin users who reported ever HRT use, which requires further investigation.