Skip to main content

Advertisement

Log in

Adherence and discontinuation of oral hormonal therapy in patients with hormone receptor positive breast cancer

  • Review Article
  • Published:
International Journal of Clinical Pharmacy Aims and scope Submit manuscript

Abstract

Background Oral treatment in women with breast cancer has been increasingly used. However, a potentially negative side of oral medication is poor patient adherence and/or discontinuation, which reduces the treatment effectiveness, accelerating progression of the disease and reducing the patient survival rate. Aim of the review To compare the rates of adherence and/or discontinuation and the methodologies used to assess these outcomes. It was conducted an integrative review of original articles published from 2000 to 2012, in which their primary outcome was to quantify medication adherence and/or discontinuation of oral hormonal therapy in patients with hormone receptor positive breast cancer. Methods Original studies were searched in the PubMed/MEDLINE, Scopus, Embase and SciELO databases. The Medical Subject Heading was used to define descriptors. The descriptor “breast neoplasms” was used in all combinations. Each of the descriptors “medication adherence” and “patient compliance” were combined with each of the following descriptors “tamoxifen”, “aromatase inhibitors”, “selective estrogen receptor modulators”, or the terms “letrozole”, “anastrozole”, and “exemestane”. Results Twenty-four original articles were included. Our study showed a wide range of adherence and discontinuation rates, ranging from 45–95.7 and 12–73 %, respectively. Regarding the methodological development of the selected articles, a high prevalence (87.5 %) of prospective and/or retrospective longitudinal studies was found. In addition, there was a high prevalence of studies using a database (70.8 %). Among some of the studies, it was shown that patient adherence to hormonal therapy gradually reduces, while discontinuation increases during the treatment. Conclusions It was observed a great diversity among rates of adherence and/or discontinuation of hormonal therapy for breast cancer, which may be due to a lack of methodology standardization. Therefore, adequate and validated methods to ensure reliability of the results and allow comparison in the literature are needed. Furthermore, adherence decreases and discontinuation increases over time, suggesting the need for patient continuous education and a pharmacotherapeutic follow up by health professionals to improve these clinical outcomes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Coughlin SS, Ekwueme DU. Breast cancer as a global health concern. Cancer Epidemiol. 2009;33(5):315–8.

    Article  PubMed  Google Scholar 

  2. Montazeri A, Vahdaninia M, Harirchi I, Ebrahimi M, Khaleghi F, Jarvandi S. Quality of life in patients with breast cancer before and after diagnosis: an eighteen months follow-up study. BMC Cancer. 2008;8:330.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Miaskowski C, Shockney L, Chlebowski RT. Adherence to oral endocrine therapy for breast cancer: a nursing perspective. Clin J Oncol Nurs. 2008;12(2):213–21.

    Article  PubMed  Google Scholar 

  4. Maughan KL, Lutterbie MA, Ham PS. Treatment of breast cancer. Am Fam Physician. 2010;81(11):1339–46.

    PubMed  Google Scholar 

  5. Partridge AH, Avorn J, Wang PS, Winer EP. Adherence to therapy with oral antineoplastic agents. J Natl Cancer Inst. 2002;94(9):652–61.

    Article  PubMed  Google Scholar 

  6. Early breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15 year survival: an overview of the randomized trials. Lancet. 2005;365(2):1687–717.

    Google Scholar 

  7. Crivellari D, Sun Z, Coates AS, Price KN, Thurlimann B, Mouridsen H, et al. Letrozole compared with tamoxifen for elderly patients with endocrine-responsive early breast cancer: the BIG 1-98 trial. J Clin Oncol. 2008;26(12):1972–9.

    Article  CAS  PubMed  Google Scholar 

  8. Forbes JF, Cuzick J, Buzdar A, Howell A, Tobias JS, Baum M. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol. 2008;9(1):45–53.

    Article  PubMed  Google Scholar 

  9. Thompson AM, Johnson A, Quinlan P, Hillman G, Fontecha M, Bray SE, et al. Comprehensive CYP2D6 genotype and adherence affect outcome in breast cancer patients treated with tamoxifen monotherapy. Breast Cancer Res Treat. 2011;125(1):279–87.

    Article  CAS  PubMed  Google Scholar 

  10. Demissie S, Silliman RA, Lash TL. Adjuvant tamoxifen: predictors of use side effects, and discontinuation in older women. J Clin Oncol. 2001;19(2):322–8.

    CAS  PubMed  Google Scholar 

  11. Grunfeld EA, Hunter MS, Sikka P, Mittal S. Adherence beliefs among breast cancer patients taking tamoxifen. Patient Educ Couns. 2005;59(1):97–102.

    Article  PubMed  Google Scholar 

  12. Lash TL, Fox MP, Westrup JL, Fink AK, Silliman RA. Adherence to tamoxifen over the five-year course. Breast Cancer Res Treat. 2006;99(2):215–20.

    Article  PubMed  Google Scholar 

  13. Bedell CH. A changing paradigm for cancer treatment: the advent of new oral chemotherapy agents. Clin J Oncol Nurs. 2003;7(6 Suppl):5–9.

    Article  PubMed  Google Scholar 

  14. Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL. Principles of Internal Medicine. 2006;1: 16th edn. ISBN 85-86804-54-1.

  15. Partridge AH, LaFountain A, Mayer E, Taylor BS, Winer E, Asnis-Alibozek A. Adherence to initial adjuvant anastrozole therapy among women with early-stage breast cancer. J Clin Oncol. 2008;26(4):556–62.

    Article  CAS  PubMed  Google Scholar 

  16. Owusu C, Buist DS, Field TS, Lash TL, Thwin SS, Geiger AM, et al. Predictors of tamoxifen discontinuation among older women with estrogen receptor–positive breast cancer. J Clin Oncol. 2008;26(4):549–55.

    Article  PubMed  Google Scholar 

  17. Font R, Espinas JA, Gil–Gil M, Barnadas A, Ojeda B, Tusquets I, et al. Prescription refill, patient self-report and physician report in assessing adherence to oral endocrine therapy in early breast cancer patients: a retrospective cohort study in Catalonia, Spain. Br J Cancer. 2012;107(8):1249–56.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Huiart L, Bouhnik AD, Rey D, Tarpin C, Cluze C, Bendiane MK, et al. Early discontinuation of tamoxifen intake in younger women with breast cancer: is it time to rethink the way it is prescribed? Eur J Cancer. 2012;48(13):1939–46.

    Article  PubMed  Google Scholar 

  19. Gotay C, Dunn J. Adherence to long-term adjuvant hormonal therapy for breast cancer. Expert Rev Pharmacoecon Outcomes Res. 2011;11(6):709–15.

    Article  PubMed  Google Scholar 

  20. Murphy CC, Bartholomew LK, Carpentier MY, Bluethmann SM, Vernon SW. Adherence to adjuvant hormonal therapy among breast cancer survivors in clinical practice: a systematic review. Breast Cancer Res Treat. 2012;134(2):459–78. doi:10.1007/s10549-012-2114-5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Whittemore R, Knafl K. The integrative review: updated methodology. J Adv Nurs. 2005;52(5):546–53.

    Article  PubMed  Google Scholar 

  22. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol. 2009;62(10):e1–34.

    Article  PubMed  Google Scholar 

  23. Organization World Health. Adherence to long-term therapies. Evidence for action. Geneva: WHO; 2003 ISBN 92 4 154599 2.

    Google Scholar 

  24. Bugalho A, Carneiro, AV. Intervenções para aumentar a adesão terapêutica em patologias crónicas. Lisboa: Faculdade de Medicina de Lisboa, 2004 [Interventions to enhance medication adherence in chronic conditions. Lisbon: Faculty of Medicine of Lisbon, 2004]. ISSN 1074-308.

  25. Kardas P, Morrison V, Fargher E, Parveens S, Plumpton C, Clyne W, et al. Report on the determinants of patients non-adherence with short-term therapies and long-term treatments. Chapter 3: determinants of patients non-adherence. ABC Project: Ascertaining Barriers for Compliance, 2012.

  26. Vrijens B, De Geest S, Hughes D, Kardas P, Demonceau J, Ruppar T, et al. A new taxonomy for describing and defining adherence to medications. Br J Clin Pharmacol. 2012;73(5):691–705.

    Article  PubMed  Google Scholar 

  27. Moher D, Liberati A, Tetzlaff J, Altman DG. PRSIMA Group (2009) Preferred reporting items for systematic reviews and meta- analyses: the PRISMA statement. J Clin Epidemiol. 2012;62(10):1006–12.

    Article  Google Scholar 

  28. Wigertz A, Ahlgren J, Holmqvist M, Fornander T, Adolfsson J, Lindman H, et al. Adherence and discontinuation of adjuvant hormonal therapy in breast cancer patients: a population-based study. Breast Cancer Res Treat. 2012;133(1):367–73.

    Article  CAS  PubMed  Google Scholar 

  29. Cluze C, Rey D, Huiart L, BenDiane MK, Bouhnik AD, Berenger C, et al. Adjuvant endocrine therapy with tamoxifen in young women with breast cancer: determinants of interruptions vary over time. Ann Oncol. 2012;23(4):882–90.

    Article  CAS  PubMed  Google Scholar 

  30. Hershman DL, Shao T, Kushi LH, Buono D, Tsai WY, Fehrenbacher L, et al. Early discontinuation and non-adherence to adjuvant hormonal therapy are associated with increased mortality in women with breast cancer. Breast Cancer Res Treat. 2011;126(2):529–37.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Huiart L, Dell’Aniello S, Suissa S. Use of tamoxifen and aromatase inhibitors in a large population-based cohort of women with breast cancer. Br J Cancer. 2011;104(10):1558–63.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Nekhlyudov L, Li L, Ross-Degnan D, Wagner AK. Five-year patterns of adjuvant hormonal therapy use, persistence, and adherence among insured women with early-stage breast cancer. Breast Cancer Res Treat. 2011;130(2):81–9.

    Article  Google Scholar 

  33. Neugut AI, Subar M, Wilde ET, Stratton S, Brouse CH, Hillyer GC, et al. Association between prescription co-payment amount and compliance with adjuvant hormonal therapy in women with early-stage breast cancer. J Clin Oncol. 2011;29(18):2534–42.

    Article  PubMed  Google Scholar 

  34. Sedjo RL, Devine S. Predictors of non-adherence to aromatase inhibitors among commercially insured women with breast cancer. Breast Cancer Res Treat. 2011;125(1):191–200.

    Article  CAS  PubMed  Google Scholar 

  35. Dezentjé VO, Van Blijderveen NJ, Gelderblom H, Putter H, Van Herk-Sukel MP, Casparie MK, et al. Effect of concomitant CYP2D6 inhibitor use and tamoxifen adherence on breast cancer recurrence in early-stage breast cancer. J Clin Oncol. 2010;28(14):423–9.

    Article  Google Scholar 

  36. Van Herk-Sukel MP, Van de Poll-Franse LV, Voogd AC, Nieuwenhuijzen GA, Coebergh JW, Herings RM. Half of breast cancer patients discontinue tamoxifen and any endocrine treatment before the end of the recommended treatment period of 5 years: a population-based analysis. Breast Cancer Res Treat. 2010;122(3):843–51.

    Article  PubMed  Google Scholar 

  37. Kimmick G, Anderson R, Camacho F, Bhosle M, Hwang W, Balkrishnan R. Adjuvant hormonal therapy use among insured, low-income women with breast cancer. J Clin Oncol. 2009;27(21):3445–51.

    Article  PubMed  Google Scholar 

  38. Ma AM, Barone J, Wallis AE, Wu NJ, Garcia LB, Estabrook A, et al. Noncompliance with adjuvant radiation, chemotherapy, or hormonal therapy in breast cancer patients. Am J Surg. 2008;196(4):500–4.

    Article  PubMed  Google Scholar 

  39. Barron TI, Connolly R, Bennett K, Feely J, Kennedy MJ. Early discontinuation of tamoxifen: a lesson for oncologists. Cancer. 2007;109(5):832–9.

    Article  CAS  PubMed  Google Scholar 

  40. Kahn KL, Schneider EC, Malin JL, Adams JL, Epstein AM. Patient centered experiences in breast cancer: predicting long-term adherence to tamoxifen use. Med Care. 2007;45(5):431–9.

    Article  PubMed  Google Scholar 

  41. Atkins L, Fallowfield L. Intentional and non-intentional non-adherence to medication amongst breast cancer patients. Eur J Cancer. 2006;42(14):2271–6.

    Article  PubMed  Google Scholar 

  42. Fink AK, Gurwitz J, Rakowski W, Guadagnoli E, Silliman RA. Patient beliefs and tamoxifen discontinuance in older women with estrogen receptor-positive breast cancer. J Clin Oncol. 2004;22(16):3309–15.

    Article  PubMed  Google Scholar 

  43. Partridge AH, Wang PS, Winer EP, Avorn J. Nonadherence to adjuvant tamoxifen therapy in women with primary breast cancer. J Clin Oncol. 2003;21(4):602–6.

    Article  CAS  PubMed  Google Scholar 

  44. Waterhouse DM, Calzone KA, Mele C, Brener DE. Adherence to oral tamoxifen non-compliance: a comparation of patient self-report, pill counts, and microelectronic monitoring. J Clin Oncol. 1993;11:1189–97.

    CAS  PubMed  Google Scholar 

  45. Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005;353(5):487–97.

    Article  CAS  PubMed  Google Scholar 

  46. Buzdar A. Anastrozole as adjuvant therapy for early-stage breast cancer: implications of the ATAC trial. Clin Breast Cancer. 2003;4(Suppl 1):S42–8.

    Article  CAS  PubMed  Google Scholar 

  47. Kaplow R. Innovations in antineoplastic therapy. Nurs Clin N Am. 2005;40(1):77–94.

    Article  Google Scholar 

  48. Moore S. Nonadherence in patients with breast cancer receiving oral therapies. Clin J Oncol Nurs. 2010;14(1):41–7.

    Article  PubMed  Google Scholar 

  49. Obreli-Neto PR, Baldoni AO, Guidoni CM, Bergamini D, Hernandes KC, da Luz RT, et al. Métodos de avaliação de adesão à farmacoterapia [Methods for estimating adherence to the pharmacotherapy]. Rev Bras Farm. 2012;93(4):403–10.

    Google Scholar 

  50. Schneeweiss S, Avorn J. A review of uses of health care utilization databases for epidemiologic research on therapeutics. J Clin Epidemiol. 2005;58(4):323–37.

    Article  PubMed  Google Scholar 

  51. Hall GC, Sauer B, Bourke A, Brown JS, Reynolds MW, LoCasale R. Guidelines for good database selection and use in pharmacoepidemiology research. Pharmacoepidemiol Drug Saf. 2012;21(1):1–10.

    Article  PubMed  Google Scholar 

  52. Gold DT. Approaches to patient education: emphasizing the long-term value of compliance and persistence. Am J Med. 2006;119(4 Suppl 1):S32–7.

    Article  PubMed  Google Scholar 

  53. Clyne W, Mshelia C, McLachlan S, Clyne W, Geest S, Ruppar T, et al. Exploring the current practices of adherence management by healthcare professionals and the pharmaceutical industry. Chapter 5: determinants of patients non-adherence. ABC Project: Ascertaining Barriers for Compliance, 2012.

  54. Hepler CD. Clinical pharmacy, pharmaceutical care, and the quality of drug therapy. Pharmacotherapy. 2004;24(11):1491–8.

    Article  PubMed  Google Scholar 

  55. Borges APS, Guidoni CM, Ferreira LD, Freitas O, Pereira LRL. The pharmaceutical care of patients with type 2 diabetes mellitus. Pharm World Sci. 2010;32(6):730–6.

    Article  PubMed  Google Scholar 

  56. Obreli-Neto PR, Guidoni CM, Baldoni AO, Pilger D, Cruciol-Souza JM, Gaeti-Franco WP, et al. Effect of a 36-month pharmaceutical care program on pharmacotherapy adherence in elderly diabetic and hypertensive patients. Int J Clin Pharm. 2011;33(4):642–9.

    Article  PubMed  Google Scholar 

  57. Hirsch JD, Gonzales M, Rosenquist A, Miller TA, Gilmer TP, Best BM. Antiretroviral therapy adherence, medication use, and health care costs during 3 years of a community pharmacy medication therapy management program for Medi-Cal beneficiaries with HIV/AIDS. J Manag Care Pharm. 2011;17(3):213–23.

    PubMed  Google Scholar 

  58. Liekweg A, Westfeld M, Braun M, Zivanovic O, Schink T, Kuhn W, et al. Pharmaceutical care for patients with breast and ovarian cancer. Support Care Cancer. 2012;20(11):2669–77.

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank the School of Pharmaceutical Sciences of Ribeirão Preto—University of São Paulo for its support during the research.

Funding

National Council for Scientific and Technological Development (CNPq), Brazil.

Conflicts of interest

None to declare.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lorena Rocha Ayres.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ayres, L.R., Baldoni, A.O., Borges, A.P.S. et al. Adherence and discontinuation of oral hormonal therapy in patients with hormone receptor positive breast cancer. Int J Clin Pharm 36, 45–54 (2014). https://doi.org/10.1007/s11096-013-9833-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11096-013-9833-5

Keywords

Navigation