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Erschienen in: Breast Cancer Research and Treatment 1/2012

01.08.2012 | Epidemiology

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

verfasst von: Krishna Undela, Vallakatla Srikanth, Dipika Bansal

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 1/2012

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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.
Literatur
2.
Zurück zum Zitat Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90PubMedCrossRef Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90PubMedCrossRef
4.
Zurück zum Zitat 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 286:11314–11327PubMedCrossRef 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 286:11314–11327PubMedCrossRef
5.
Zurück zum Zitat 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 22:749–758PubMedCrossRef 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 22:749–758PubMedCrossRef
6.
Zurück zum Zitat 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 71:1763–1771PubMedCrossRef 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 71:1763–1771PubMedCrossRef
7.
Zurück zum Zitat 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 11:409PubMedCrossRef 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 11:409PubMedCrossRef
8.
Zurück zum Zitat 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 360:1623–1630PubMedCrossRef 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 360:1623–1630PubMedCrossRef
9.
Zurück zum Zitat 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 364:771–777PubMedCrossRef 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 364:771–777PubMedCrossRef
10.
Zurück zum Zitat 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 160:2363–2368PubMedCrossRef 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 160:2363–2368PubMedCrossRef
11.
Zurück zum Zitat 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) 12:749–756CrossRef 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) 12:749–756CrossRef
12.
Zurück zum Zitat Lovastatin Study Groups I through IV (1993) Lovastatin 5-year safety and efficacy study. Arch Intern Med 153:1079–1087CrossRef Lovastatin Study Groups I through IV (1993) Lovastatin 5-year safety and efficacy study. Arch Intern Med 153:1079–1087CrossRef
13.
Zurück zum Zitat Beck P, Wysowski DK, Downey W, Butler-Jones D (2003) Statin use and the risk of breast cancer. J Clin Epidemiol 56:280–285PubMedCrossRef Beck P, Wysowski DK, Downey W, Butler-Jones D (2003) Statin use and the risk of breast cancer. J Clin Epidemiol 56:280–285PubMedCrossRef
14.
Zurück zum Zitat Graaf MR, Beiderbeck AB, Egberts AC, Richel DJ, Guchelaar HJ (2004) The risk of cancer in users of statins’. J Clin Oncol 22:2388–2394PubMedCrossRef Graaf MR, Beiderbeck AB, Egberts AC, Richel DJ, Guchelaar HJ (2004) The risk of cancer in users of statins’. J Clin Oncol 22:2388–2394PubMedCrossRef
15.
Zurück zum Zitat Kaye JA, Jick H (2004) Statin use and cancer risk in the general practice research database. Br J Cancer 90:635–637PubMedCrossRef Kaye JA, Jick H (2004) Statin use and cancer risk in the general practice research database. Br J Cancer 90:635–637PubMedCrossRef
16.
Zurück zum Zitat 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 114:643–647PubMedCrossRef 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 114:643–647PubMedCrossRef
17.
Zurück zum Zitat 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 100:2308–2316PubMedCrossRef 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 100:2308–2316PubMedCrossRef
18.
Zurück zum Zitat 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 23:8606–8612PubMedCrossRef 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 23:8606–8612PubMedCrossRef
19.
Zurück zum Zitat 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 165:2264–2271PubMedCrossRef 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 165:2264–2271PubMedCrossRef
20.
Zurück zum Zitat 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 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
21.
Zurück zum Zitat 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 98:700–707PubMedCrossRef 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 98:700–707PubMedCrossRef
22.
Zurück zum Zitat 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 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
23.
Zurück zum Zitat 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 71:1763–1771PubMedCrossRef 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 71:1763–1771PubMedCrossRef
24.
Zurück zum Zitat 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 16:416–421PubMedCrossRef 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 16:416–421PubMedCrossRef
25.
Zurück zum Zitat Coogan PF, Rosenberg L, Strom BL (2007) Statin use and the risk of 10 cancers. Epidemiology 18:213–219PubMedCrossRef Coogan PF, Rosenberg L, Strom BL (2007) Statin use and the risk of 10 cancers. Epidemiology 18:213–219PubMedCrossRef
26.
Zurück zum Zitat 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 67:99–109PubMedCrossRef 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 67:99–109PubMedCrossRef
27.
Zurück zum Zitat Eaton M, Eklof J, Beal JR, Sahmoun AE (2009) Statins’ and breast cancer in postmenopausal women without hormone therapy. Anticancer Res 29:5143–5148PubMed Eaton M, Eklof J, Beal JR, Sahmoun AE (2009) Statins’ and breast cancer in postmenopausal women without hormone therapy. Anticancer Res 29:5143–5148PubMed
28.
Zurück zum Zitat 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:c2197PubMedCrossRef 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:c2197PubMedCrossRef
29.
Zurück zum Zitat 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 115:27–33PubMedCrossRef 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 115:27–33PubMedCrossRef
30.
Zurück zum Zitat 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 17:27–36PubMedCrossRef 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 17:27–36PubMedCrossRef
31.
Zurück zum Zitat Pocobelli G, Newcomb PA, Trentham-Dietz A, Titus-Ernstoff L, Hampton JM, Egan KM (2008) Statin use and risk of breast cancer. Cancer 112:27–33PubMedCrossRef Pocobelli G, Newcomb PA, Trentham-Dietz A, Titus-Ernstoff L, Hampton JM, Egan KM (2008) Statin use and risk of breast cancer. Cancer 112:27–33PubMedCrossRef
32.
Zurück zum Zitat 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 126:279–284PubMedCrossRef 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 126:279–284PubMedCrossRef
33.
Zurück zum Zitat Woditschka S, Habel LA, Udaltsova N, Friedman GD, Sieh W (2010) Lipophilic statin use and risk of breast cancer subtypes. Cancer Epidemiol Biomarkers Prev 19:2479–2487PubMedCrossRef Woditschka S, Habel LA, Udaltsova N, Friedman GD, Sieh W (2010) Lipophilic statin use and risk of breast cancer subtypes. Cancer Epidemiol Biomarkers Prev 19:2479–2487PubMedCrossRef
34.
Zurück zum Zitat 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 11:409PubMedCrossRef 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 11:409PubMedCrossRef
35.
Zurück zum Zitat Coogan PF, Rosenberg L, Palmer JR, Strom BL, Zauber AG, Shapiro S (2002) Statin use and the risk of breast and prostate cancer. Epidemiology 13:262–267PubMedCrossRef Coogan PF, Rosenberg L, Palmer JR, Strom BL, Zauber AG, Shapiro S (2002) Statin use and the risk of breast and prostate cancer. Epidemiology 13:262–267PubMedCrossRef
36.
Zurück zum Zitat Kaye JA, Meier CR, Walker AM, Jick H (2002) Statin use, hyperlipidaemia, and the risk of breast cancer. Br J Cancer 86:1436–1439PubMedCrossRef Kaye JA, Meier CR, Walker AM, Jick H (2002) Statin use, hyperlipidaemia, and the risk of breast cancer. Br J Cancer 86:1436–1439PubMedCrossRef
37.
Zurück zum Zitat Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50:1088–1101PubMedCrossRef Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50:1088–1101PubMedCrossRef
38.
Zurück zum Zitat Egger M, Davey SG, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634PubMedCrossRef Egger M, Davey SG, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634PubMedCrossRef
39.
Zurück zum Zitat Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560PubMedCrossRef Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560PubMedCrossRef
40.
Zurück zum Zitat Altman DG, Bland JM (2003) Interaction revisited: the difference between two estimates. BMJ 326:219PubMedCrossRef Altman DG, Bland JM (2003) Interaction revisited: the difference between two estimates. BMJ 326:219PubMedCrossRef
41.
Zurück zum Zitat 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 283:2008–2012PubMedCrossRef 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 283:2008–2012PubMedCrossRef
42.
Zurück zum Zitat 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 109:573–579PubMedCrossRef 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 109:573–579PubMedCrossRef
43.
Zurück zum Zitat 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 29:585–593PubMedCrossRef 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 29:585–593PubMedCrossRef
44.
Zurück zum Zitat 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 16:508–519PubMedCrossRef 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 16:508–519PubMedCrossRef
45.
Zurück zum Zitat Chan KK, Oza AM, Siu LL (2003) The statins’ as anticancer agents. Clin Cancer Res 9:10–19PubMed Chan KK, Oza AM, Siu LL (2003) The statins’ as anticancer agents. Clin Cancer Res 9:10–19PubMed
46.
48.
Zurück zum Zitat Hamelin BA, Turgeon J (1998) Hydrophilicity/lipophilicity: relevance for the pharmacology and clinical effects of HMG-CoA reductase inhibitors. Trends Pharmacol Sci 19:26–37PubMedCrossRef Hamelin BA, Turgeon J (1998) Hydrophilicity/lipophilicity: relevance for the pharmacology and clinical effects of HMG-CoA reductase inhibitors. Trends Pharmacol Sci 19:26–37PubMedCrossRef
Metadaten
Titel
Statin use and risk of breast cancer: a meta-analysis of observational studies
verfasst von
Krishna Undela
Vallakatla Srikanth
Dipika Bansal
Publikationsdatum
01.08.2012
Verlag
Springer US
Erschienen in
Breast Cancer Research and Treatment / Ausgabe 1/2012
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-012-2154-x

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