Đang tải... (xem toàn văn)
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.
Skarping et al BMC Cancer (2015) 15:435 DOI 10.1186/s12885-015-1457-9 RESEARCH ARTICLE Open Access Effects of statin use on volumetric mammographic density: results from the KARMA study Ida Skarping1, Judith S Brand2, Per Hall2 and Signe Borgquist1,3* Abstract 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™ 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 Keywords: Volumetric mammographic density, Statins, Screening-based cohort, Epidemiology, Breast cancer Background Statins are inhibitors of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase and are used worldwide as an efficient cholesterol-lowering medication with proven anti-inflammatory properties [1] By reducing HMG-CoA reductase activity, levels of mevalonate decrease, which influences important down-stream players for cellular pathways that are crucial for cancer initiation, growth, and metastasis [2] Pre-clinical studies and phase II trials have demonstrated anti-carcinogenic properties of statins [3–5] Large-scale epidemiological observational studies have reported conflicting findings regarding the * Correspondence: signe.borgquist@med.lu.se Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Skåne University Hospital, SE-221 85 Lund, Sweden Department of Oncology, Skåne University Hospital, Lund, Sweden Full list of author information is available at the end of the article role of statins in breast cancer prevention [6–11] On the other hand, available data on breast cancer prognosis are more consistent showing a lower risk of recurrence in lipophilic statin users [12–14] These data suggest that statins may not prevent cancer occurrence, e.g by affecting the malignant genotype, but rather inhibit the progress of an existing cancer by affecting the malignant phenotype [11] Mammographic density (MD), which reflects the amount of fibroglandular or radio dense tissue on an X-ray of the breast (mammogram), is a strong determinant of breast cancer risk [15, 16] Women with extremely dense breasts (>75 % dense tissue on a mammogram) have a 4–6 fold higher risk of developing breast cancer compared to women having fatty or non-dense breasts (