Post-diagnosis statin use and breast cancer recurrence in a prospective cohort study of early stage breast cancer survivors

Abstract

Purpose

We examined the association between post-diagnosis statin use (3-hydroxy-3-methylglutaryl-coenzyme A [HMG-CoA] inhibitors) and risk of breast cancer recurrence.

Materials and methods

The study included 1945 early stage breast cancer survivors participating in the Life After Cancer Epidemiology (LACE) Study. Women who were diagnosed from 1997 to 2000 and identified from the Kaiser Permanente Northern California (KPNC) Cancer Registry entered the cohort on average 2 years post-diagnosis. Information on statin use was obtained from the KPNC pharmacy database. A total of 210 breast cancer recurrences were reported and verified by medical record review. Cox proportional hazard models were used to estimate rate ratios (RR) and 95% confidence intervals (CI).

Results

The mean duration of statin use in the cohort among those who initiated use post-diagnosis was 1.96 years, and lipophilic statins were mainly used (97.8%). Starting statins after diagnosis was suggestive of a decreased risk of breast cancer recurrence (RR = 0.67; 95% CI: 0.39–1.13). Risk of recurrence decreased with increasing duration of statin use after diagnosis (p linear trend = 0.02).

Conclusion

Our findings provide initial support for an inverse association between post-diagnosis, lipophilic statin use and risk of breast cancer recurrence.

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References

  1. 1.

    Baigent C, Keech A, Kearney PM et al (2005) Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 366(9493):1267–1278

    PubMed  Article  CAS  Google Scholar 

  2. 2.

    Campbell MJ, Esserman LJ, Zhou Y et al (2006) Breast cancer growth prevention by statins. Cancer Res 66(17):8707–8714

    PubMed  Article  CAS  Google Scholar 

  3. 3.

    Beck P, Wysowski DK, Downey W, Butler-Jones D (2003) Statin use and the risk of breast cancer. J Clin Epidemiol 56(3):280–285

    PubMed  Article  Google Scholar 

  4. 4.

    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(11):2308–2316

    PubMed  Article  CAS  Google Scholar 

  5. 5.

    Cauley JA, McTiernan A, Rodabough RJ et al (2006) Statin use and breast cancer: prospective results from the Womens Health Initiative. J Natl Cancer Inst 98(10):700–707

    PubMed  CAS  Article  Google Scholar 

  6. 6.

    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(3):262–267

    PubMed  Article  Google Scholar 

  7. 7.

    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(19):2264–2271

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    Friis S, Poulsen AH, Johnsen SP et al (2005) Cancer risk among statin users: a population-based cohort study. Int J Cancer 114(4):643–647

    PubMed  Article  CAS  Google Scholar 

  9. 9.

    Graaf MR, Beiderbeck AB, Egberts AC, Richel DJ, Guchelaar HJ (2004) The risk of cancer in users of statins. J Clin Oncol 22(12):2388–2394

    PubMed  Article  CAS  Google Scholar 

  10. 10.

    Kaye JA, Jick H (2004) Statin use and cancer risk in the general practice research database. Br J Cancer 90(3):635–637

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    Caan B, Sternfeld B, Gunderson E, Coates A, Quesenberry C, Slattery ML (2005) Life after cancer epidemiology (LACE) study: a cohort of early stage breast cancer survivors (United States). Cancer Causes Control 16(5):545–556

    PubMed  Article  Google Scholar 

  12. 12.

    Allison PD (1995) Survival analysis using SAS: a practical guide. SAS Press, Cary, NC

    Google Scholar 

  13. 13.

    Hosmer DW, Lemeshow S (1999) Applied survival analysis: regression modeling of time to event data. Wiley, New York

    Google Scholar 

  14. 14.

    Demierre MF, Higgins PD, Gruber SB, Hawk E, Lippman SM (2005) Statins and cancer prevention. Nat Rev Cancer 5(12):930–942

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    Katz MS (2005) Therapy insight: potential of statins for cancer chemoprevention and therapy. Nat Clin Pract Oncol 2(2):82–89

    PubMed  Article  CAS  Google Scholar 

  16. 16.

    Duncan RE, El-Sohemy A, Archer MC (2005) Statins and cancer development. Cancer Epidemiol Biomarkers Prev 14(8):1897–1898

    PubMed  Article  CAS  Google Scholar 

  17. 17.

    Esserman L, Campbell M, Shoemaker M, Lobo M, Marx C, Benz C (2004) Breast cancer inhibition by statins. J Clin Oncol 22(97s):(Suppl; abstr 1003)

  18. 18.

    Mueck AO, Seeger H, Wallwiener D (2003) Effect of statins combined with estradiol on the proliferation of human receptor-positive and receptor-negative breast cancer cells. Menopause 10(4):332–336

    PubMed  Article  Google Scholar 

  19. 19.

    Seeger H, Wallwiener D, Mueck AO (2003) Statins can inhibit proliferation of human breast cancer cells in vitro. Exp Clin Endocrinol Diabetes 111(1):47–48

    PubMed  Article  CAS  Google Scholar 

  20. 20.

    Kumar AS, Campbell M, Benz CC, Esserman LJ (2006) A call for clinical trials: lipophilic statins may prove effective in treatment and prevention of particular breast cancer subtypes. J Clin Oncol 24(13):2127; author reply 2127–2128

    Google Scholar 

  21. 21.

    Alonso DF, Farina HG, Skilton G, Gabri MR, De Lorenzo MS, Gomez DE (1998) Reduction of mouse mammary tumor formation and metastasis by lovastatin, an inhibitor of the mevalonate pathway of cholesterol synthesis. Breast Cancer Res Treat 50(1):83–93

    PubMed  Article  CAS  Google Scholar 

  22. 22.

    Farina HG, Bublik DR, Alonso DF, Gomez DE (2002) Lovastatin alters cytoskeleton organization and inhibits experimental metastasis of mammary carcinoma cells. Clin Exp Metastasis 19(6):551–559

    PubMed  Article  CAS  Google Scholar 

  23. 23.

    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(34):8606–8612

    PubMed  Article  Google Scholar 

  24. 24.

    Kochhar R, Khurana V, Bejjanki H, Caldito G, Fort C (2005) Statins to reduce breast cancer risk: A case control study in US female veterans. J Clin Oncol 23(7s):(Suppl; abstr 514)

  25. 25.

    Mortimer J, Axelrod R, Zimbro K (2004) Effect of statins on breast cancer incidence: findings from the Sentara Health Plan. Proc Am Soc Clin Oncol 22(93):(abstr 373)

  26. 26.

    Selby JV, Smith DH, Johnson ES, Raebel MA, Friedman GD, McFarland BH (2005) Kaiser permanente medical care program. In: BL S (ed) Pharmacoepidemiology. Wiley, West Sussex, pp 241–259

    Google Scholar 

  27. 27.

    Setoguchi S, Avorn J, Schneeweiss S (2005) Statins and the risk of colorectal cancer. N Engl J Med 353(9):952–954; author reply 952–954

    Google Scholar 

  28. 28.

    The Internet Drug Index http://www.rxlist.com [Last accessed: December 12, 2006]

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Acknowledgments

This study was funded by the National Cancer Institute (R01 CA80027) and by the Utah Cancer Registry (N01 PC67000), with additional support from the State of Utah Department of Health. We thank Natalia Udaltsova and Erin Weltzien for statistical programming support. We thank all LACE Study staff and participants. Financial Support: National Cancer Institute (R01 CA80027 and N01-PC-67000).

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Correspondence to Marilyn L. Kwan.

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Kwan, M.L., Habel, L.A., Flick, E.D. et al. 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 (2008). https://doi.org/10.1007/s10549-007-9683-8

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Keywords

  • Statins
  • HMG-CoA inhibitors
  • Breast cancer
  • Recurrence
  • Prognosis