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Statin use and risk of breast cancer: a meta-analysis of observational studies

  • Epidemiology
  • Published:
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Abstract

Emerging evidence suggests that statins’ may decrease the risk of cancers. However, available evidence on breast cancer is conflicting. We, therefore, examined the association between statin use and risk of breast cancer by conducting a detailed meta-analysis of all observational studies published regarding this subject. PubMed database and bibliographies of retrieved articles were searched for epidemiological studies published up to January 2012, investigating the relationship between statin use and breast cancer. Before meta-analysis, the studies were evaluated for publication bias and heterogeneity. Combined relative risk (RR) and 95 % confidence interval (CI) were calculated using a random-effects model (DerSimonian and Laird method). Subgroup analyses, sensitivity analysis, and cumulative meta-analysis were also performed. A total of 24 (13 cohort and 11 case–control) studies involving more than 2.4 million participants, including 76,759 breast cancer cases contributed to this analysis. We found no evidence of publication bias and evidence of heterogeneity among the studies. Statin use and long-term statin use did not significantly affect breast cancer risk (RR = 0.99, 95 % CI = 0.94, 1.04 and RR = 1.03, 95 % CI = 0.96, 1.11, respectively). When the analysis was stratified into subgroups, there was no evidence that study design substantially influenced the effect estimate. Sensitivity analysis confirmed the stability of our results. Cumulative meta-analysis showed a change in trend of reporting risk of breast cancer from positive to negative in statin users between 1993 and 2011. Our meta-analysis findings do not support the hypothesis that statins’ have a protective effect against breast cancer. More randomized clinical trials and observational studies are needed to confirm this association with underlying biological mechanisms in the future.

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References

  1. World Health Organization (2011) CancerStats Cancer worldwide. http://info.cancerresearchuk.org/cancerstats/world/. Accessed 7 February 2011

  2. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90

    Article  PubMed  Google Scholar 

  3. Lamb E (2009) Top 200 drugs of 2008. http://www.pharmacytimes.com/issue/pharmacy/2009/2009-05/RxFocusTop200Drugs-0509. Accessed 7 February 2011

  4. Mandal CC, Ghosh-Choudhury N, Yoneda T, Choudhury GG (2011) Simvastatin prevents skeletal metastasis of breast cancer by an antagonistic interplay between p53 and CD44. J Biol Chem 286:11314–11327

    Article  PubMed  CAS  Google Scholar 

  5. Ghosh-Choudhury N, Mandal CC, Ghosh Choudhury G (2010) Simvastatin induces derepression of PTEN expression via NFkappaB to inhibit breast cancer cell growth. Cell Signal 22:749–758

    Article  PubMed  CAS  Google Scholar 

  6. Jacobs EJ, Newton CC, Thun MJ, Gapstur SM (2011) Long-term use of cholesterol-lowering drugs and cancer incidence in a large United States cohort. Cancer Res 71:1763–1771

    Article  PubMed  CAS  Google Scholar 

  7. Vinogradova Y, Coupland C, Hippisley-Cox J (2011) Exposure to statins’ and risk of common cancers: a series of nested case-control studies. BMC Cancer 11:409

    Article  PubMed  Google Scholar 

  8. Shepherd J, Blauw GJ, Murphy MB, Bollen EL, Buckley BM, Cobbe SM, Ford I, Gaw A, Hyland M, Jukema JW, Kamper AM, Macfarlane PW, Meinders AE, Norrie J, Packard CJ, Perry IJ, Stott DJ, Sweeney BJ, Twomey C, Westendorp RG (2002) Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 360:1623–1630

    Article  PubMed  CAS  Google Scholar 

  9. Strandberg TE, Pyorala K, Cook TJ, Wilhelmsen L, Faergeman O, Thorgeirsson G, Pedersen TR, Kjekshus J (2004) Mortality and incidence of cancer during 10-year follow-up of the Scandinavian Simvastatin Survival Study (4S). Lancet 364:771–777

    Article  PubMed  CAS  Google Scholar 

  10. Blais L, Desgagné A, LeLorier J (2000) 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and the risk of cancer: a nested case-control study. Arch Intern Med 160:2363–2368

    Article  PubMed  CAS  Google Scholar 

  11. Cauley JA, Zmuda JM, Lui LY, Hillier TA, Ness RB, Stone KL, Cummings SR, Bauer DC (2003) Lipid-lowering drug use and breast cancer in older women: a prospective study. J Womens Health (Larchmt) 12:749–756

    Article  Google Scholar 

  12. Lovastatin Study Groups I through IV (1993) Lovastatin 5-year safety and efficacy study. Arch Intern Med 153:1079–1087

    Article  Google Scholar 

  13. Beck P, Wysowski DK, Downey W, Butler-Jones D (2003) Statin use and the risk of breast cancer. J Clin Epidemiol 56:280–285

    Article  PubMed  Google Scholar 

  14. Graaf MR, Beiderbeck AB, Egberts AC, Richel DJ, Guchelaar HJ (2004) The risk of cancer in users of statins’. J Clin Oncol 22:2388–2394

    Article  PubMed  CAS  Google Scholar 

  15. Kaye JA, Jick H (2004) Statin use and cancer risk in the general practice research database. Br J Cancer 90:635–637

    Article  PubMed  CAS  Google Scholar 

  16. Friis S, Poulsen AH, Johnsen SP, McLaughlin JK, Fryzek JP, Dalton SO, Sorensen HT, Olsen JH (2005) Cancer risk among statin users: a population-based cohort study. Int J Cancer 114:643–647

    Article  PubMed  CAS  Google Scholar 

  17. Boudreau DM, Gardner JS, Malone KE, Heckbert SR, Blough DK, Daling JR (2004) The association between 3-hydroxy-3-methylglutaryl conenzyme A inhibitor use and breast carcinoma risk among postmenopausal women: a case-control study. Cancer 100:2308–2316

    Article  PubMed  CAS  Google Scholar 

  18. Bonovas S, Filioussi K, Tsavaris N, Sitaras NM (2005) Use of statins’ and breast cancer: a meta-analysis of seven randomized clinical trials and nine observational studies. J Clin Oncol 23:8606–8612

    Article  PubMed  Google Scholar 

  19. Eliassen AH, Colditz GA, Rosner B, Willett WC, Hankinson SE (2005) Serum lipids, lipid-lowering drugs, and the risk of breast cancer. Arch Intern Med 165:2264–2271

    Article  PubMed  CAS  Google Scholar 

  20. Kochhar R, Khurana V, Bejjanki H, Caldito G, Fort C (2005) Statins’ reduce breast cancer risk: a case control study in US female veterans. J Clin Oncol 23(Suppl 1):16S, Abstract 514

    Google Scholar 

  21. Cauley JA, McTiernan A, Rodabough RJ, LaCroix A, Bauer DC, Margolis KL, Paskett ED, Vitolins MZ, Furberg CD, Chlebowski RT (2006) Statin use and breast cancer: prospective results from the Women’s Health Initiative. J Natl Cancer Inst 98:700–707

    Article  PubMed  CAS  Google Scholar 

  22. Dumasia L, Lobocki C, Couturier A, Lebeis C, Derlichman A (2006) Use of statins’ and breast carcinoma: a case–control study. J Clin Oncol 24(Suppl 20):18S, Abstract 592

    Google Scholar 

  23. Jacobs EJ, Newton CC, Thun MJ, Gapstur SM (2011) Long-term use of cholesterol-lowering drugs and cancer incidence in a large United States cohort. Cancer Res 71:1763–1771

    Article  PubMed  CAS  Google Scholar 

  24. Boudreau DM, Yu O, Miglioretti DL, Buist DS, Heckbert SR, Daling JR (2007) Statin use and breast cancer risk in a large population-based setting. Cancer Epidemiol Biomarkers Prev 16:416–421

    Article  PubMed  CAS  Google Scholar 

  25. Coogan PF, Rosenberg L, Strom BL (2007) Statin use and the risk of 10 cancers. Epidemiology 18:213–219

    Article  PubMed  Google Scholar 

  26. Smeeth L, Douglas I, Hall AJ, Hubbard R, Evans S (2008) Effect of statins’ on a wide range of health outcomes: a cohort study validated by comparison with randomized trials. Br J Clin Pharmacol 67:99–109

    Article  PubMed  Google Scholar 

  27. Eaton M, Eklof J, Beal JR, Sahmoun AE (2009) Statins’ and breast cancer in postmenopausal women without hormone therapy. Anticancer Res 29:5143–5148

    PubMed  CAS  Google Scholar 

  28. Hippisley-Cox J, Coupland C (2010) Unintended effects of statins’ in men and women in England and Wales: population based cohort study using the QResearch database. BMJ 340:c2197

    Article  PubMed  Google Scholar 

  29. Setoguchi S, Glynn RJ, Avorn J, Mogun H, Schneeweiss S (2007) Statins’ and the risk of lung, breast, and colorectal cancer in the elderly. Circulation 115:27–33

    Article  PubMed  CAS  Google Scholar 

  30. Friedman GD, Flick ED, Udaltsova N, Chan J, Quesenberry CP, Habel LA (2008) Screening statins’ for possible carcinogenic risk: up to 9 years of follow-up of 361,859 recipients. Pharmacoepidemiol Drug Saf 17:27–36

    Article  PubMed  Google Scholar 

  31. Pocobelli G, Newcomb PA, Trentham-Dietz A, Titus-Ernstoff L, Hampton JM, Egan KM (2008) Statin use and risk of breast cancer. Cancer 112:27–33

    Article  PubMed  Google Scholar 

  32. Haukka J, Sankila R, Klaukka T, Lonnqvist J, Niskanen L, Tanskanen A, Wahlbeck K, Tiihonen J (2010) Incidence of cancer and statin usage record linkage study. Int J Cancer 126:279–284

    Article  PubMed  CAS  Google Scholar 

  33. Woditschka S, Habel LA, Udaltsova N, Friedman GD, Sieh W (2010) Lipophilic statin use and risk of breast cancer subtypes. Cancer Epidemiol Biomarkers Prev 19:2479–2487

    Article  PubMed  CAS  Google Scholar 

  34. Vinogradova Y, Coupland C, Hippisley-Cox J (2011) Exposure to statins’ and risk of common cancers: a series of nested case-control studies. BMC Cancer 11:409

    Article  PubMed  Google Scholar 

  35. Coogan PF, Rosenberg L, Palmer JR, Strom BL, Zauber AG, Shapiro S (2002) Statin use and the risk of breast and prostate cancer. Epidemiology 13:262–267

    Article  PubMed  Google Scholar 

  36. Kaye JA, Meier CR, Walker AM, Jick H (2002) Statin use, hyperlipidaemia, and the risk of breast cancer. Br J Cancer 86:1436–1439

    Article  PubMed  CAS  Google Scholar 

  37. Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50:1088–1101

    Article  PubMed  CAS  Google Scholar 

  38. Egger M, Davey SG, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    Article  PubMed  CAS  Google Scholar 

  39. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560

    Article  PubMed  Google Scholar 

  40. Altman DG, Bland JM (2003) Interaction revisited: the difference between two estimates. BMJ 326:219

    Article  PubMed  Google Scholar 

  41. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. meta-analysis of observational studies in epidemiology (MOOSE) group. JAMA 283:2008–2012

    Article  PubMed  CAS  Google Scholar 

  42. Kwan ML, Habel LA, Flick ED, Quesenberry CP, Caan B (2008) Post-diagnosis statin use and breast cancer recurrence in a prospective cohort study of early stage breast cancer survivors. Breast Cancer Res Treat 109:573–579

    Article  PubMed  CAS  Google Scholar 

  43. Chae YK, Valsecchi ME, Kim J, Bianchi AL, Khemasuwan D, Desai A, Tester W (2011) Reduced risk of breast cancer recurrence in patients using ACE inhibitors, ARBs, and/or statins’. Cancer Invest 29:585–593

    Article  PubMed  CAS  Google Scholar 

  44. Wong WW, Dimitroulakos J, Minden MD, Penn LZ (2002) HMG-CoA reductase inhibitors and the malignant cell: the statin family of drugs as triggers of tumor-specific apoptosis. Leukemia 16:508–519

    Article  PubMed  CAS  Google Scholar 

  45. Chan KK, Oza AM, Siu LL (2003) The statins’ as anticancer agents. Clin Cancer Res 9:10–19

    PubMed  CAS  Google Scholar 

  46. Newman TB, Hulley SB (1996) Carcinogenicity of lipid-lowering drugs. JAMA 275:55–60

    Article  PubMed  CAS  Google Scholar 

  47. Rogers MJ (2000) Statins’: lower lipids and better bones? Nat Med 6:21–23

    Article  PubMed  CAS  Google Scholar 

  48. Hamelin BA, Turgeon J (1998) Hydrophilicity/lipophilicity: relevance for the pharmacology and clinical effects of HMG-CoA reductase inhibitors. Trends Pharmacol Sci 19:26–37

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors thank Dr. Dimple Kondal, Senior scientist (Biostatistician), Centre for excellence, Public Health Foundation, India, for helping with the data analysis and Ms. Sahaja Banda for checking the accuracy of English usage.

Conflict of interest

No potential conflicts of interest relevant to this article were reported. No funding was provided for the analysis.

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Authors and Affiliations

  1. Department of Pharmacy Practice, National Institute of Pharmaceutical Education and Research, SAS Nagar, Punjab, India

    Krishna Undela, Vallakatla Srikanth & Dipika Bansal

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  1. Krishna Undela
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Correspondence to Krishna Undela.

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Undela, K., Srikanth, V. & Bansal, D. Statin use and risk of breast cancer: a meta-analysis of observational studies. Breast Cancer Res Treat 135, 261–269 (2012). https://doi.org/10.1007/s10549-012-2154-x

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