Skip to main content
Erschienen in: Archives of Osteoporosis 1/2019

01.12.2019 | Original Article

Oral bisphosphonate use and the risk of female breast, ovarian, and cervical cancer: a nationwide population-based cohort study

verfasst von: Ye Seul Bae, Jooyoung Chang, Sang Min Park

Erschienen in: Archives of Osteoporosis | Ausgabe 1/2019

Einloggen, um Zugang zu erhalten

Abstract

Summary

Bisphosphonate use was not associated with the risk of female breast, ovarian, or cervical cancer. The results according to bisphosphonate type or concurrent drug uses were not associated with the cancer risk. The protective effect of bisphosphonate use on female breast cancer was significant in the low comorbidity group.

Purpose

Despite the antitumor mechanisms, the effect of bisphosphonates on the risk of cancer is still unclear. We investigated the association between oral bisphosphonate use and the development of female breast, ovarian, and cervical cancer.

Methods

We accomplished a population-based cohort study using the National Health Insurance Services (NHIS) database. A total of 204,525 participants were included in a cohort, and we identified the incident cases of each cancer from 2007 to 2013. We assessed cumulative bisphosphonate exposure from 2003 to 2006 using the defined daily dose (DDD) system. Hazard ratios (HRs) and their 95% confidence intervals (CIs) were presented to assess the association between bisphosphonate use and cancer incidence using multivariate Cox proportional hazard regression models. Subgroup analyses were performed to assess cancer development according to risk factors and concurrent drug use.

Results

There was a total of 1547, 266, and 370 incident cases of female breast, cervical, and ovarian cancer, respectively, during the study period of 1,367,294 person-years. Bisphosphonate exposure was not significantly associated with risk of female breast (adjusted HR (aHR), 0.78; 95% CI, 0.60–1.02), ovarian (aHR, 1.30; 95% CI, 0.82–2.07), nor cervical cancer (aHR, 0.70; 95% CI, 0.44–1.12). Further subgroup analyses also revealed no statistically significant effects of bisphosphonate use with various risk factors and concurrent drug use.

Conclusions

Our study showed no significant associations between bisphosphonate exposure and female breast, cervical, and ovarian cancer. In the future, large prospective studies or a meta-analysis would be needed to verify the associations.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Lewiecki EM (2010) Bisphosphonates for the treatment of osteoporosis: insights for clinicians. Ther Adv Chronic Dis 1(3):115–128CrossRef Lewiecki EM (2010) Bisphosphonates for the treatment of osteoporosis: insights for clinicians. Ther Adv Chronic Dis 1(3):115–128CrossRef
2.
Zurück zum Zitat Clézardin P, Ebetino FH, Fournier PG (2005) Bisphosphonates and cancer-induced bone disease: beyond their antiresorptive activity. Cancer Res 65(12):4971–4974CrossRef Clézardin P, Ebetino FH, Fournier PG (2005) Bisphosphonates and cancer-induced bone disease: beyond their antiresorptive activity. Cancer Res 65(12):4971–4974CrossRef
3.
Zurück zum Zitat Boissier S, Ferreras M, Peyruchaud O, Magnetto S, Ebetino FH, Colombel M et al (2000) Bisphosphonates inhibit breast and prostate carcinoma cell invasion, an early event in the formation of bone metastases. Cancer Res 60(11):2949–2954PubMed Boissier S, Ferreras M, Peyruchaud O, Magnetto S, Ebetino FH, Colombel M et al (2000) Bisphosphonates inhibit breast and prostate carcinoma cell invasion, an early event in the formation of bone metastases. Cancer Res 60(11):2949–2954PubMed
4.
Zurück zum Zitat Roelofs AJ, Thompson K, Gordon S, Rogers MJ (2006) Molecular mechanisms of action of bisphosphonates: current status. Clin Cancer Res 12(20):6222s–6230sCrossRef Roelofs AJ, Thompson K, Gordon S, Rogers MJ (2006) Molecular mechanisms of action of bisphosphonates: current status. Clin Cancer Res 12(20):6222s–6230sCrossRef
5.
Zurück zum Zitat Newcomb P, Trentham-Dietz A, Hampton J (2010) Bisphosphonates for osteoporosis treatment are associated with reduced breast cancer risk. Br J Cancer 102(5):799–802CrossRef Newcomb P, Trentham-Dietz A, Hampton J (2010) Bisphosphonates for osteoporosis treatment are associated with reduced breast cancer risk. Br J Cancer 102(5):799–802CrossRef
6.
Zurück zum Zitat Cardwell CR, Abnet CC, Veal P, Hughes CM, Cantwell MM, Murray LJ (2012) Exposure to oral bisphosphonates and risk of cancer. Int J Cancer 131(5):E717–E725CrossRef Cardwell CR, Abnet CC, Veal P, Hughes CM, Cantwell MM, Murray LJ (2012) Exposure to oral bisphosphonates and risk of cancer. Int J Cancer 131(5):E717–E725CrossRef
7.
Zurück zum Zitat Chlebowski RT, Chen Z, Cauley JA, Anderson G, Rodabough RJ, McTiernan A, Lane DS, Manson JAE, Snetselaar L, Yasmeen S, O’Sullivan MJ, Safford M, Hendrix SL, Wallace RB (2010) Oral bisphosphonate use and breast cancer incidence in postmenopausal women. J Clin Oncol 28(22):3582–3590CrossRef Chlebowski RT, Chen Z, Cauley JA, Anderson G, Rodabough RJ, McTiernan A, Lane DS, Manson JAE, Snetselaar L, Yasmeen S, O’Sullivan MJ, Safford M, Hendrix SL, Wallace RB (2010) Oral bisphosphonate use and breast cancer incidence in postmenopausal women. J Clin Oncol 28(22):3582–3590CrossRef
8.
Zurück zum Zitat Vestergaard P, Fischer L, Mele M, Mosekilde L, Christiansen P (2011) Use of bisphosphonates and risk of breast cancer. Calcif Tissue Int 88(4):255–262CrossRef Vestergaard P, Fischer L, Mele M, Mosekilde L, Christiansen P (2011) Use of bisphosphonates and risk of breast cancer. Calcif Tissue Int 88(4):255–262CrossRef
9.
Zurück zum Zitat Ou YJ, Chiu HF, Wong YH, Yang CC, Yang YH (2017) Bisphosphonate use and the risk of breast cancer: a meta-analysis of observational studies. Pharmacoepidemiol Drug Saf 26(10):1286–1295CrossRef Ou YJ, Chiu HF, Wong YH, Yang CC, Yang YH (2017) Bisphosphonate use and the risk of breast cancer: a meta-analysis of observational studies. Pharmacoepidemiol Drug Saf 26(10):1286–1295CrossRef
10.
Zurück zum Zitat Monsees GM, Malone KE, Tang M-TC, Newcomb PA, Li CI (2011) Bisphosphonate use after estrogen receptor–positive breast cancer and risk of contralateral breast cancer. J Natl Cancer Inst 103(23):1752–1760CrossRef Monsees GM, Malone KE, Tang M-TC, Newcomb PA, Li CI (2011) Bisphosphonate use after estrogen receptor–positive breast cancer and risk of contralateral breast cancer. J Natl Cancer Inst 103(23):1752–1760CrossRef
11.
Zurück zum Zitat Vinogradova Y, Coupland C, Hippisley-Cox J (2013) Exposure to bisphosphonates and risk of common non-gastrointestinal cancers: series of nested case–control studies using two primary-care databases. Br J Cancer 109(3):795–806CrossRef Vinogradova Y, Coupland C, Hippisley-Cox J (2013) Exposure to bisphosphonates and risk of common non-gastrointestinal cancers: series of nested case–control studies using two primary-care databases. Br J Cancer 109(3):795–806CrossRef
12.
Zurück zum Zitat Rennert G, Pinchev M, Rennert HS (2010) Use of bisphosphonates and risk of postmenopausal breast cancer. J Clin Oncol 28(22):3577–3581CrossRef Rennert G, Pinchev M, Rennert HS (2010) Use of bisphosphonates and risk of postmenopausal breast cancer. J Clin Oncol 28(22):3577–3581CrossRef
13.
Zurück zum Zitat Newcomb PA, Passarelli MN, Phipps AI, Anderson GL, Wactawski-Wende J, Ho GY et al (2015) Oral bisphosphonate use and risk of postmenopausal endometrial cancer. J Clin Oncol 33(10):1186–1190CrossRef Newcomb PA, Passarelli MN, Phipps AI, Anderson GL, Wactawski-Wende J, Ho GY et al (2015) Oral bisphosphonate use and risk of postmenopausal endometrial cancer. J Clin Oncol 33(10):1186–1190CrossRef
14.
Zurück zum Zitat Alford SH, Rattan R, Buekers TE, Munkarah AR (2015) Protective effect of bisphosphonates on endometrial cancer incidence in data from the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial. Cancer. 121(3):441–447CrossRef Alford SH, Rattan R, Buekers TE, Munkarah AR (2015) Protective effect of bisphosphonates on endometrial cancer incidence in data from the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial. Cancer. 121(3):441–447CrossRef
15.
Zurück zum Zitat Rennert G, Rennert HS, Pinchev M, Lavie O (2014) The effect of bisphosphonates on the risk of endometrial and ovarian malignancies. Gynecol Oncol 133(2):309–313CrossRef Rennert G, Rennert HS, Pinchev M, Lavie O (2014) The effect of bisphosphonates on the risk of endometrial and ovarian malignancies. Gynecol Oncol 133(2):309–313CrossRef
16.
Zurück zum Zitat Hue TF, Cummings SR, Cauley JA, Bauer DC, Ensrud KE, Barrett-Connor E, Black DM (2014) Effect of bisphosphonate use on risk of postmenopausal breast cancer: results from the randomized clinical trials of alendronate and zoledronic acid. JAMA Intern Med 174(10):1550–1557CrossRef Hue TF, Cummings SR, Cauley JA, Bauer DC, Ensrud KE, Barrett-Connor E, Black DM (2014) Effect of bisphosphonate use on risk of postmenopausal breast cancer: results from the randomized clinical trials of alendronate and zoledronic acid. JAMA Intern Med 174(10):1550–1557CrossRef
17.
Zurück zum Zitat Chiang CH, Huang CC, Chan WL, Huang PH, Chen TJ, Chung CM, Lin SJ, Chen JW, Leu HB (2012) Oral alendronate use and risk of cancer in postmenopausal women with osteoporosis: a nationwide study. J Bone Miner Res 27(9):1951–1958CrossRef Chiang CH, Huang CC, Chan WL, Huang PH, Chen TJ, Chung CM, Lin SJ, Chen JW, Leu HB (2012) Oral alendronate use and risk of cancer in postmenopausal women with osteoporosis: a nationwide study. J Bone Miner Res 27(9):1951–1958CrossRef
18.
Zurück zum Zitat Lee W-Y, Sun L-M, Lin M-C, Liang J-A, Chang S-N, Sung F-C, Muo CH, Kao CH (2012) A higher dosage of oral alendronate will increase the subsequent cancer risk of osteoporosis patients in Taiwan: a population-based cohort study. PLoS One 7(12):e53032CrossRef Lee W-Y, Sun L-M, Lin M-C, Liang J-A, Chang S-N, Sung F-C, Muo CH, Kao CH (2012) A higher dosage of oral alendronate will increase the subsequent cancer risk of osteoporosis patients in Taiwan: a population-based cohort study. PLoS One 7(12):e53032CrossRef
19.
Zurück zum Zitat Torre LA, Siegel RL, Ward EM, Jemal A (2016) Global cancer incidence and mortality rates and trends—an update. Cancer Epidemiology and Prevention Biomarkers 25(1):16–27CrossRef Torre LA, Siegel RL, Ward EM, Jemal A (2016) Global cancer incidence and mortality rates and trends—an update. Cancer Epidemiology and Prevention Biomarkers 25(1):16–27CrossRef
20.
Zurück zum Zitat Shin J-Y, Park M-J, Lee SH, Choi S-H, Kim M-H, Choi N-K et al (2015) Risk of intracranial haemorrhage in antidepressant users with concurrent use of non-steroidal anti-inflammatory drugs: nationwide propensity score matched study. BMJ 351:h3517CrossRef Shin J-Y, Park M-J, Lee SH, Choi S-H, Kim M-H, Choi N-K et al (2015) Risk of intracranial haemorrhage in antidepressant users with concurrent use of non-steroidal anti-inflammatory drugs: nationwide propensity score matched study. BMJ 351:h3517CrossRef
21.
Zurück zum Zitat World Health Organization (2006) The anatomical therapeutic chemical classification system with defined daily doses (ATC/DDD). WHO, Oslo World Health Organization (2006) The anatomical therapeutic chemical classification system with defined daily doses (ATC/DDD). WHO, Oslo
22.
Zurück zum Zitat Quan H, Sundararajan V, Halfon P, Fong A, Burnand B, Luthi J-C, Saunders LD, Beck CA, Feasby TE, Ghali WA (2005) Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Med Care 43:1130–1139CrossRef Quan H, Sundararajan V, Halfon P, Fong A, Burnand B, Luthi J-C, Saunders LD, Beck CA, Feasby TE, Ghali WA (2005) Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Med Care 43:1130–1139CrossRef
23.
Zurück zum Zitat Who EC (2004) Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet (London, England) 363(9403):157CrossRef Who EC (2004) Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet (London, England) 363(9403):157CrossRef
24.
Zurück zum Zitat Park B, Sung J, Park K, Seo S, Kim S (2003) Report of the evaluation for validity of discharged diagnoses in Korean Health Insurance database. Seoul National University, Seoul, pp 19–52 Park B, Sung J, Park K, Seo S, Kim S (2003) Report of the evaluation for validity of discharged diagnoses in Korean Health Insurance database. Seoul National University, Seoul, pp 19–52
25.
Zurück zum Zitat Clézardin P (2011) Bisphosphonates’ antitumor activity: an unravelled side of a multifaceted drug class. Bone. 48(1):71–79CrossRef Clézardin P (2011) Bisphosphonates’ antitumor activity: an unravelled side of a multifaceted drug class. Bone. 48(1):71–79CrossRef
26.
Zurück zum Zitat Yancik R, Wesley MN, Ries LA, Havlik RJ, Edwards BK, Yates JW (2001) Effect of age and comorbidity in postmenopausal breast cancer patients aged 55 years and older. JAMA 285(7):885–892CrossRef Yancik R, Wesley MN, Ries LA, Havlik RJ, Edwards BK, Yates JW (2001) Effect of age and comorbidity in postmenopausal breast cancer patients aged 55 years and older. JAMA 285(7):885–892CrossRef
27.
Zurück zum Zitat Giraudo E, Inoue M, Hanahan D (2004) An amino-bisphosphonate targets MMP-9–expressing macrophages and angiogenesis to impair cervical carcinogenesis. J Clin Invest 114(5):623–633CrossRef Giraudo E, Inoue M, Hanahan D (2004) An amino-bisphosphonate targets MMP-9–expressing macrophages and angiogenesis to impair cervical carcinogenesis. J Clin Invest 114(5):623–633CrossRef
28.
Zurück zum Zitat Drake MT, Clarke BL, Khosla S (2008: Elsevier) Bisphosphonates: mechanism of action and role in clinical practice. Mayo Clin Proc 83:1032–1045CrossRef Drake MT, Clarke BL, Khosla S (2008: Elsevier) Bisphosphonates: mechanism of action and role in clinical practice. Mayo Clin Proc 83:1032–1045CrossRef
29.
Zurück zum Zitat Dunford JE, Thompson K, Coxon FP, Luckman SP, Hahn FM, Poulter CD et al (2001) Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates. J Pharmacol Exp Ther 296(2):235–242PubMed Dunford JE, Thompson K, Coxon FP, Luckman SP, Hahn FM, Poulter CD et al (2001) Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates. J Pharmacol Exp Ther 296(2):235–242PubMed
30.
Zurück zum Zitat Kim M-h, Chang J, Kim WJ, Banerjee S, Park SM (2018) Cumulative dose threshold for the chemopreventive effect of aspirin against gastric cancer. Am J Gastroenterol 113(6):845PubMed Kim M-h, Chang J, Kim WJ, Banerjee S, Park SM (2018) Cumulative dose threshold for the chemopreventive effect of aspirin against gastric cancer. Am J Gastroenterol 113(6):845PubMed
Metadaten
Titel
Oral bisphosphonate use and the risk of female breast, ovarian, and cervical cancer: a nationwide population-based cohort study
verfasst von
Ye Seul Bae
Jooyoung Chang
Sang Min Park
Publikationsdatum
01.12.2019
Verlag
Springer London
Erschienen in
Archives of Osteoporosis / Ausgabe 1/2019
Print ISSN: 1862-3522
Elektronische ISSN: 1862-3514
DOI
https://doi.org/10.1007/s11657-019-0588-z

Weitere Artikel der Ausgabe 1/2019

Archives of Osteoporosis 1/2019 Zur Ausgabe

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie. Erweitert durch Fallbeispiele, Videos und Abbildungen. 
» Jetzt entdecken

Update Orthopädie und Unfallchirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.