Advertisement

Breast Cancer Research and Treatment

, Volume 156, Issue 2, pp 379–389 | Cite as

Effectiveness of bisphosphonate use and risk of contralateral breast cancer and recurrence in women with early-stage breast cancer treated with tamoxifen

  • Marilyn L. KwanEmail author
  • Jiaxiao M. Shi
  • Laurel A. Habel
  • Jun Song
  • Joanie W-L Chung
  • Chantal C. Avila
  • Joanne E. Schottinger
  • T. Craig Cheetham
  • Suzanne W. Fletcher
  • Reina Haque
Epidemiology

Abstract

The effectiveness of bisphosphonates (BP) in reducing risk of second breast cancer and recurrence in observational studies has been minimally studied. We examined the association of oral BP use on risk of contralateral breast cancer (CBC) and recurrence in 16,781 women diagnosed with early-stage breast cancer from 1996 to 2007, treated with tamoxifen, and followed through December 31, 2009 at Kaiser Permanente Northern California (KPNC, n = 8857) and Southern California (KPSC, n = 7924). Sociodemographic, clinical, and pharmacy information were extracted from electronic medical records and cancer registries. CBC was identified from cancer registries, and recurrences from electronic health records and chart reviews. Multivariate Cox regression models were used to estimate hazard ratios (HR) and 95 % confidence intervals (CI) treating BP use and hormonal therapy as time-varying variables. After mean 6.4 years of follow-up, 494 (3.0 %) women developed CBC. BP use post-breast cancer diagnosis (>93 % alendronate) ranged from 14.5 to 24.9 % at both study sites. Overall, there was no association of BP use with reduced risk of CBC (ever use, HR = 0.96; 95 % CI 0.67–1.38 and continuous use, HR = 1.03; 95 % CI 0.88, 1.20). Similar null associations were observed for recurrence (ever use, HR = 0.98; 95 % CI 0.82, 1.17 and continuous use, HR = 1.00; 95 % CI 0.92, 1.09). Associations varied somewhat by site yet confidence intervals overlapped. BP use was not associated with reduced risk of recurrence or new primary disease among women diagnosed with early breast cancer and treated with tamoxifen.

Keywords

Breast cancer Bisphosphonates Alendronate Contralateral breast cancer Second primary cancers Cohort study 

Notes

Acknowledgments

This work was supported by the National Cancer Institute (R01 CA136743 to R.H.). We thank Erin Weltzien and Cecile Laurent for additional programming support. The contents of this article are solely the responsibility of the authors and do not represent the official views of the funding agencies.

Funding

NIH, NCI R01 CA136743 (“Antidepressants and Breast Cancer Pharmacoepidemiology”).

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.

References

  1. 1.
    Chen Y, Semenciw R, Kliewer E, Shi Y, Mao Y (2001) Incidence of second primary breast cancer among women with a first primary in Manitoba, Canada. Breast Cancer Res Treat 67(1):35–40CrossRefPubMedGoogle Scholar
  2. 2.
    Chen Y, Thompson W, Semenciw R, Mao Y (1999) Epidemiology of contralateral breast cancer. Cancer Epidemiol Biomark Prev 8(10):855–861Google Scholar
  3. 3.
    Mellemkjaer L, Friis S, Olsen JH, Scelo G, Hemminki K, Tracey E, Andersen A, Brewster DH, Pukkala E, McBride ML, Kliewer EV, Tonita JM, Kee-Seng C, Pompe-Kirn V, Martos C, Jonasson JG, Boffetta P, Brennan P (2006) Risk of second cancer among women with breast cancer. Int J Cancer. Journal international du cancer 118(9):2285–2292CrossRefPubMedGoogle Scholar
  4. 4.
    Yu GP, Schantz SP, Neugut AI, Zhang ZF (2006) Incidences and trends of second cancers in female breast cancer patients: a fixed inception cohort-based analysis (United States). Cancer Causes Control 17(4):411–420CrossRefPubMedGoogle Scholar
  5. 5.
    Raymond JS, Hogue CJ (2006) Multiple primary tumours in women following breast cancer, 1973-2000. Br J Cancer 94(11):1745–1750PubMedPubMedCentralGoogle Scholar
  6. 6.
    Rosen CJ (2005) Clinical practice. postmenopausal osteoporosis. N Engl J Med 353(6):595–603CrossRefPubMedGoogle Scholar
  7. 7.
    Siris ES, Pasquale MK, Wang Y, Watts NB (2011) Estimating bisphosphonate use and fracture reduction among US women aged 45 years and older, 2001-2008. J Bone mineral Res 26(1):3–11CrossRefGoogle Scholar
  8. 8.
    Aapro M, Abrahamsson PA, Body JJ, Coleman RE, Colomer R, Costa L, Crino L, Dirix L, Gnant M, Gralow J, Hadji P, Hortobagyi GN, Jonat W, Lipton A, Monnier A, Paterson AH, Rizzoli R, Saad F, Thurlimann B (2008) Guidance on the use of bisphosphonates in solid tumours: recommendations of an international expert panel. Ann Oncol 19(3):420–432CrossRefPubMedGoogle Scholar
  9. 9.
    Body JJ (2006) Breast cancer: bisphosphonate therapy for metastatic bone disease. Clin Cancer Res 12(20 Pt 2):6258s–6263sCrossRefPubMedGoogle Scholar
  10. 10.
    Van Poznak CH, Temin S, Yee GC, Janjan NA, Barlow WE, Biermann JS, Bosserman LD, Geoghegan C, Hillner BE, Theriault RL, Zuckerman DS, Von Roenn JH (2011) American Society of Clinical Oncology executive summary of the clinical practice guideline update on the role of bone-modifying agents in metastatic breast cancer. J Clin Oncol 29(9):1221–1227CrossRefPubMedGoogle Scholar
  11. 11.
    Russell RG, Xia Z, Dunford JE, Oppermann U, Kwaasi A, Hulley PA, Kavanagh KL, Triffitt JT, Lundy MW, Phipps RJ, Barnett BL, Coxon FP, Rogers MJ, Watts NB, Ebetino FH (2007) Bisphosphonates: an update on mechanisms of action and how these relate to clinical efficacy. Ann N Y Acad Sci 1117:209–257CrossRefPubMedGoogle Scholar
  12. 12.
    Winter MC, Holen I, Coleman RE (2008) Exploring the anti-tumour activity of bisphosphonates in early breast cancer. Cancer Treat Rev 34(5):453–475CrossRefPubMedGoogle Scholar
  13. 13.
    Neville-Webbe HL, Gnant M, Coleman RE (2010) Potential anticancer properties of bisphosphonates. Semin Oncol 37(Suppl 1):S53–S65CrossRefPubMedGoogle Scholar
  14. 14.
    Winter MC, Coleman RE (2013) Bisphosphonates in the adjuvant treatment of breast cancer. Clin Oncol 25(2):135–145CrossRefGoogle Scholar
  15. 15.
    Chlebowski RT, Chen Z, Cauley JA, Anderson G, Rodabough RJ, McTiernan A, Lane DS, Manson JE, 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):3582–3590CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Newcomb PA, Trentham-Dietz A, Hampton JM (2010) Bisphosphonates for osteoporosis treatment are associated with reduced breast cancer risk. Br J Cancer 102(5):799–802CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Rennert G, Pinchev M, Rennert HS (2010) Use of bisphosphonates and risk of postmenopausal breast cancer. J Clin Oncol 28(22):3577–3581CrossRefPubMedGoogle Scholar
  18. 18.
    Vestergaard P, Fischer L, Mele M, Mosekilde L, Christiansen P (2011) Use of bisphosphonates and risk of breast cancer. Calcif Tissue Int 88(4):255–262CrossRefPubMedGoogle Scholar
  19. 19.
    Pazianas M, Abrahamsen B, Eiken PA, Eastell R, Russell RG (2012) Reduced colon cancer incidence and mortality in postmenopausal women treated with an oral bisphosphonate—Danish National Register Based Cohort Study. Osteoporos Int 23(11):2693–2701CrossRefPubMedGoogle Scholar
  20. 20.
    Rennert G, Pinchev M, Rennert HS, Gruber SB (2011) Use of bisphosphonates and reduced risk of colorectal cancer. J Clin Oncol 29(9):1146–1150CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Singh H, Nugent Z, Demers A, Mahmud S, Bernstein C (2012) Exposure to bisphosphonates and risk of colorectal cancer: a population-based nested case-control study. Cancer 118(5):1236–1243CrossRefPubMedGoogle Scholar
  22. 22.
    Green J, Czanner G, Reeves G, Watson J, Wise L, Beral V (2010) Oral bisphosphonates and risk of cancer of oesophagus, stomach, and colorectum: case-control analysis within a UK primary care cohort. BMJ 341:c4444CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Monsees GM, Malone KE, Tang MT, 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):1752–1760CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Haque R, Shi J, Schottinger JE, Ahmed SA, Cheetham TC, Chung J, Avila C, Kleinman K, Habel LA, Fletcher SW, Kwan ML (2015) Tamoxifen and antidepressant drug interaction in a cohort of 16,887 breast cancer survivors. J Natl Cancer Inst 108(3). doi: 10.1093/jnci/djv337 Google Scholar
  25. 25.
    Haque R, Shi J, Schottinger JE, Ahmed SA, Chung J, Avila C, Lee VS, Cheetham TC, Habel LA, Fletcher SW, Kwan ML (2015) A hybrid approach to identify subsequent breast cancer using pathology and automated health information data. Med Care 53(4):380–385CrossRefPubMedGoogle Scholar
  26. 26.
    Singal AG, Higgins PD, Waljee AK (2014) A primer on effectiveness and efficacy trials. Clin Transl Gastroenterol 5:e45CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Coleman R (2011) The use of bisphosphonates in cancer treatment. Ann N Y Acad Sci 1218:3–14CrossRefPubMedGoogle Scholar
  28. 28.
    Coleman R, de Boer R, Eidtmann H, Llombart A, Davidson N, Neven P, von Minckwitz G, Sleeboom HP, Forbes J, Barrios C, Frassoldati A, Campbell I, Paija O, Martin N, Modi A, Bundred N (2012) Zoledronic acid (zoledronate) for postmenopausal women with early breast cancer receiving adjuvant letrozole (ZO-FAST study): final 60-month results. Ann Oncol 24(2):398–405CrossRefPubMedGoogle Scholar
  29. 29.
    Gnant M, Mlineritsch B, Schippinger W, Luschin-Ebengreuth G, Postlberger S, Menzel C, Jakesz R, Seifert M, Hubalek M, Bjelic-Radisic V, Samonigg H, Tausch C, Eidtmann H, Steger G, Kwasny W, Dubsky P, Fridrik M, Fitzal F, Stierer M, Rucklinger E, Greil R, Marth C (2009) Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N Engl J Med 360(7):679–691CrossRefPubMedGoogle Scholar
  30. 30.
    Gnant M, Mlineritsch B, Stoeger H, Luschin-Ebengreuth G, Heck D, Menzel C, Jakesz R, Seifert M, Hubalek M, Pristauz G, Bauernhofer T, Eidtmann H, Eiermann W, Steger G, Kwasny W, Dubsky P, Hochreiner G, Forsthuber EP, Fesl C, Greil R (2011) Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 62-month follow-up from the ABCSG-12 randomised trial. Lancet Oncol 12(7):631–641CrossRefPubMedGoogle Scholar
  31. 31.
    Paterson AH, Anderson SJ, Lembersky BC, Fehrenbacher L, Falkson CI, King KM, Weir LM, Brufsky AM, Dakhil S, Lad T, Baez-Diaz L, Gralow JR, Robidoux A, Perez EA, Zheng P, Geyer CE Jr, Swain SM, Costantino JP, Mamounas EP, Wolmark N (2012) Oral clodronate for adjuvant treatment of operable breast cancer (National Surgical Adjuvant Breast and Bowel Project protocol B-34): a multicentre, placebo-controlled, randomised trial. Lancet Oncol 13(7):734–742CrossRefPubMedGoogle Scholar
  32. 32.
    Mobus V, Diel IJ, Harbeck N (2011) GAIN (German Adjuvant Intergroup Node Positive) Study: a phase III multicenter trial to compare dose dense, dose intense ETC (iddETC) vs. EC-TX and ibandronate vs. observation in patients with node-positive primary breast cancer-1st interim efficacy analysis. 2011 San Antonio Breast Cancer Symposium. Abstract S2-4Google Scholar
  33. 33.
    Early Breast Cancer Trialists’ Collaborative Group (2015) Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials. Lancet 386:1353–1361CrossRefGoogle Scholar
  34. 34.
    Suissa S (2008) Immortal time bias in pharmaco-epidemiology. Am J Epidemiol 167(4):492–499CrossRefPubMedGoogle Scholar
  35. 35.
    Dell R, Greene D, Schelkun SR, Williams K (2008) Osteoporosis disease management: the role of the orthopaedic surgeon. J Bone Joint Surg Am 90(Suppl 4):188–194CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Marilyn L. Kwan
    • 1
    Email author
  • Jiaxiao M. Shi
    • 2
  • Laurel A. Habel
    • 1
  • Jun Song
    • 3
  • Joanie W-L Chung
    • 2
  • Chantal C. Avila
    • 2
  • Joanne E. Schottinger
    • 4
  • T. Craig Cheetham
    • 2
  • Suzanne W. Fletcher
    • 5
  • Reina Haque
    • 2
  1. 1.Division of ResearchKaiser Permanente Northern CaliforniaOaklandUSA
  2. 2.Department of Research and EvaluationKaiser Permanente Southern CaliforniaPasadenaUSA
  3. 3.Data & Information Management EnhancementKaiser Permanente NorthwestPortlandUSA
  4. 4.Department of Clinical AnalysisKaiser Permanente Southern CaliforniaPasadenaUSA
  5. 5.Harvard Medical School and Harvard Pilgrim Health Care InstituteBostonUSA

Personalised recommendations