Skip to main content

Adjuvant hormonal therapy for early breast cancer: an epidemiologic study of medication adherence

Abstract

Purpose

The aim of this study was to determine the prevalence of adherence to adjuvant hormonal therapy (AHT) and to identify risk factors for medication non-adherence in clinical practice in patients with early-stage hormone receptor (HR)-positive breast cancer (BC) previously treated with chemotherapy.

Methods

We carried out a cross-sectional, observational, prospective, and multicenter survey based on a structured self-report postal questionnaire (35 items investigating six areas). A sample of 474 patients was drawn from 676 patients potentially eligible. The structured and validated Morisky Medication Adherence Scale-4 items was used for measuring medication adherence. An analysis of risk factors for non-adherence to AHT was performed using a two-step approach: univariate, then multivariate analysis.

Results

A total of 280 patients out of the 428 analyzed patients participated in the survey, yielding a response rate of 65.4% [60.9–69.9]. The prevalence of adherence to AHT was estimated at 68.6% [63.1–74.0], corresponding to a high level of adherence. Three risk factors for non-adherence to AHT were identified: > 2 medications to treat comorbidities (p-value = 0.003), age less than 65 years (p-value = 0.008), and patient management in a university hospital setting (p-value = 0.014).

Conclusions

Non-adherence is a common, complex, and multidimensional healthcare problem. This better understanding and knowledge of risk factors will allow healthcare providers (such as oncologists, general practitioners, pharmacists) to more easily identify patients at risk for non-adherence and help them provide appropriate information about AHT and its management, thus improving medication adherence in their patients.

This is a preview of subscription content, access via your institution.

Fig. 1

References

  1. Institut national du cancer (2017) Les cancers en France, édition 2016, collection Les Données

  2. Senkus E, Kyriakides S, Ohno S et al (2015) Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 26(Suppl 5):v8–30. https://doi.org/10.1093/annonc/mdv298

    Article  PubMed  Google Scholar 

  3. Early Breast Cancer Trialists’ Collaborative Group (1998) Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet 351:1451–1467

    Article  Google Scholar 

  4. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), Davies C, Godwin J et al (2011) Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet 378:771–784. https://doi.org/10.1016/S0140-6736(11)60993-8

    Article  Google Scholar 

  5. Davies C, Pan H, Godwin J et al (2013) Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet 381:805–816. https://doi.org/10.1016/S0140-6736(12)61963-1

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. Gray RG, Rea D, Handley K et al (2013) aTTom: long-term effects of continuing adjuvant tamoxifen to 10 years versusversusversus stopping at 5 years in 6953 women with early breast cancer. J Clin Oncol 31:5. https://doi.org/10.1200/jco.2013.31.15_suppl.5

    Article  Google Scholar 

  7. Goss PE, Ingle JN, Pritchard KI et al (2016) Extending aromatase-inhibitor adjuvant therapy to 10 years. N Engl J Med. https://doi.org/10.1056/NEJMoa1604700

    PubMed  PubMed Central  Google Scholar 

  8. Winer EP, Hudis C, Burstein HJ et al (2005) American Society of Clinical Oncology technology assessment on the use of aromatase inhibitors as adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer: status report 2004. J Clin Oncol 23:619–629. https://doi.org/10.1200/JCO.2005.09.121

    CAS  Article  PubMed  Google Scholar 

  9. McCowan C, Shearer J, Donnan PT et al (2008) Cohort study examining tamoxifen adherence and its relationship to mortality in women with breast cancer. Br J Cancer 99:1763–1768. https://doi.org/10.1038/sj.bjc.6604758

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 365:1687–1717. https://doi.org/10.1016/S0140-6736(05)66544-0

    Article  Google Scholar 

  11. Lebovits AH, Strain JJ, Schleifer SJ et al (1990) Patient noncompliance with self-administered chemotherapy. Cancer 65:17–22

    CAS  Article  PubMed  Google Scholar 

  12. Brier MJ, Chambless D, Gross R et al (2015) Association between self-report adherence measures and oestrogen suppression among breast cancer survivors on aromatase inhibitors. Eur J Cancer 51:1890–1896. https://doi.org/10.1016/j.ejca.2015.06.113

    CAS  Article  PubMed  Google Scholar 

  13. Murphy CC, Bartholomew LK, Carpentier MY et al (2012) Adherence to adjuvant hormonal therapy among breast cancer survivors in clinical practice: a systematic review. Breast Cancer Res Treat 134:459–478. https://doi.org/10.1007/s10549-012-2114-5

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. Verbrugghe M, Verhaeghe S, Lauwaert K et al (2013) Determinants and associated factors influencing medication adherence and persistence to oral anticancer drugs: a systematic review. Cancer Treat Rev 39:610–621. https://doi.org/10.1016/j.ctrv.2012.12.014

    CAS  Article  PubMed  Google Scholar 

  15. Puts MTE, Tu HA, Tourangeau A et al (2014) Factors influencing adherence to cancer treatment in older adults with cancer: a systematic review. Ann Oncol 25:564–577. https://doi.org/10.1093/annonc/mdt433

    CAS  Article  PubMed  Google Scholar 

  16. Tralongo P, Ferraù F, Borsellino N et al (2011) Cancer patient-centered home care: a new model for health care in oncology. Ther Clin Risk Manag 7:387–392. https://doi.org/10.2147/TCRM.S22119

    PubMed  PubMed Central  Google Scholar 

  17. Morisky DE, Green LW, Levine DM (1986) Concurrent and predictive validity of a self-reported measure of medication adherence. Med Care 24:67–74

    CAS  Article  PubMed  Google Scholar 

  18. Morisky DE, Ang A, Krousel-Wood M, Ward HJ (2008) Predictive validity of a medication adherence measure in an outpatient setting. J Clin Hypertens 10:348–354

    Article  Google Scholar 

  19. Korb-Savoldelli V, Gillaizeau F, Pouchot J et al (2012) Validation of a French version of the 8-item Morisky medication adherence scale in hypertensive adults. J Clin Hypertens 14:429–434. https://doi.org/10.1111/j.1751-7176.2012.00634.x

    Article  Google Scholar 

  20. Etter JF, Perneger TV (1997) Analysis of non-response bias in a mailed health survey. J Clin Epidemiol 50:1123–1128

    CAS  Article  PubMed  Google Scholar 

  21. van den Akker M, Buntinx F, Metsemakers JF, Knottnerus JA (1998) Morbidity in responders and non-responders in a register-based population survey. Fam Pract 15:261–263

    Article  PubMed  Google Scholar 

  22. Korkeila K, Suominen S, Ahvenainen J et al (2001) Non-response and related factors in a nation-wide health survey. Eur J Epidemiol 17:991–999

    CAS  Article  PubMed  Google Scholar 

  23. Haynes RB, Sackett DL, Taylor DW et al (1977) Manipulation of the therapeutic regimen to improve compliance: conceptions and misconceptions. Clin Pharmacol Ther 22:125–130

    CAS  Article  PubMed  Google Scholar 

  24. Darkow T, Henk HJ, Thomas SK et al (2007) Treatment interruptions and non-adherence with imatinib and associated healthcare costs: a retrospective analysis among managed care patients with chronic myelogenous leukaemia. PharmacoEconomics 25:481–496

    CAS  Article  PubMed  Google Scholar 

  25. Partridge AH, Wang PS, Winer EP, Avorn J (2003) Nonadherence to adjuvant tamoxifen therapy in women with primary breast cancer. J Clin Oncol 21:602–606

    CAS  Article  PubMed  Google Scholar 

  26. Partridge AH (2006) Non-adherence to endocrine therapy for breast cancer. Ann Oncol 17:183–184. https://doi.org/10.1093/annonc/mdj141

    CAS  Article  PubMed  Google Scholar 

  27. Owusu C, Buist DSM, Field TS et al (2008) Predictors of tamoxifen discontinuation among older women with estrogen receptor-positive breast cancer. J Clin Oncol 26:549–555. https://doi.org/10.1200/JCO.2006.10.1022

    Article  PubMed  Google Scholar 

  28. Makubate B, Donnan PT, Dewar JA et al (2013) Cohort study of adherence to adjuvant endocrine therapy, breast cancer recurrence and mortality. Br J Cancer 108:1515–1524. https://doi.org/10.1038/bjc.2013.116

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  29. Osterberg L, Blaschke T (2005) Adherence to medication. N Engl J Med 353:487–497. https://doi.org/10.1056/NEJMra050100

    CAS  Article  PubMed  Google Scholar 

  30. Cramer JA, Mattson RH, Prevey ML et al (1989) How often is medication taken as prescribed?: a novel assessment technique. JAMA 261:3273–3277. https://doi.org/10.1001/jama.1989.03420220087032

    CAS  Article  PubMed  Google Scholar 

  31. Kruse W, Koch-Gwinner P, Nikolaus T et al (1992) Measurement of drug compliance by continuous electronic monitoring: a pilot study in elderly patients discharged from hospital. J Am Geriatr Soc 40:1151–1155

    CAS  Article  PubMed  Google Scholar 

  32. Nguyen T-M-U, La Caze A, Cottrell N (2014) What are validated self-report adherence scales really measuring?: a systematic review. Br J Clin Pharmacol 77:427–445. https://doi.org/10.1111/bcp.12194

    Article  PubMed  PubMed Central  Google Scholar 

  33. Chlebowski RT, Geller ML (2006) Adherence to endocrine therapy for breast cancer. Oncology 71:1–9. https://doi.org/10.1159/000100444

    CAS  Article  PubMed  Google Scholar 

  34. Font R, Espinas JA, Gil-Gil M et al (2012) 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 107:1249–1256. https://doi.org/10.1038/bjc.2012.389

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  35. Walter T, Wang L, Chuk K et al (2013) Assessing adherence to oral chemotherapy using different measurement methods: lessons learned from capecitabine. J Oncol Pharm Pract 20:249–256. https://doi.org/10.1177/1078155213501100

    Article  PubMed  Google Scholar 

  36. Waterhouse DM, Calzone KA, Mele C, Brenner DE (1993) Adherence to oral tamoxifen: a comparison of patient self-report, pill counts, and microelectronic monitoring. J Clin Oncol 11:1189–1197

    CAS  Article  PubMed  Google Scholar 

  37. Brito C, Portela MC, de Vasconcellos MTL (2014) Adherence to hormone therapy among women with breast cancer. BMC Cancer 14:397. https://doi.org/10.1186/1471-2407-14-397

    Article  PubMed  PubMed Central  Google Scholar 

  38. Bhatta SS, Hou N, Moton ZN et al (2013) Factors associated with compliance to adjuvant hormone therapy in Black and White women with breast cancer. SpringerPlus 2:356. https://doi.org/10.1186/2193-1801-2-356

    Article  PubMed  PubMed Central  Google Scholar 

  39. Hershman DL, Kushi LH, Shao T et al (2010) Early discontinuation and nonadherence to adjuvant hormonal therapy in a cohort of 8769 early-stage breast cancer patients. J Clin Oncol 28:4120–4128. https://doi.org/10.1200/JCO.2009.25.9655

    Article  PubMed  PubMed Central  Google Scholar 

  40. Ayres LR, de Oliveira Baldoni A, de Sá Borges AP, Pereira LR (2014) Adherence and discontinuation of oral hormonal therapy in patients with hormone receptor positive breast cancer. Int J Clin Pharm 36:45–54. https://doi.org/10.1007/s11096-013-9833-5

    CAS  Article  PubMed  Google Scholar 

  41. Liu Y, Malin JL, Diamant AL et al (2013) Adherence to adjuvant hormone therapy in low-income women with breast cancer: the role of provider-patient communication. Breast Cancer Res Treat 137:829–836. https://doi.org/10.1007/s10549-012-2387-8

    CAS  Article  PubMed  Google Scholar 

  42. Jacob Arriola KR, Mason TA, Bannon KA et al (2014) Modifiable risk factors for adherence to adjuvant endocrine therapy among breast cancer patients. Patient Educ Couns 95:98–103. https://doi.org/10.1016/j.pec.2013.12.019

    Article  PubMed  Google Scholar 

  43. Kimmick G, Anderson R, Camacho F et al (2009) Adjuvant hormonal therapy use among insured, low-income women with breast cancer. J Clin Oncol 27:3445–3451. https://doi.org/10.1200/JCO.2008.19.2419

    Article  PubMed  PubMed Central  Google Scholar 

  44. Gold DT, McClung B (2006) Approaches to patient education: emphasizing the long-term value of compliance and persistence. Am J Med 119:S32–S37. https://doi.org/10.1016/j.amjmed.2005.12.021

    Article  PubMed  Google Scholar 

  45. Felton MA, van Londen GJ, Marcum ZA (2016) Medication adherence to oral cancer therapy: the promising role of the pharmacist. J Oncol Pharm Pract 22:378–381. https://doi.org/10.1177/1078155214559114

    Article  PubMed  Google Scholar 

  46. Hurtado-de-Mendoza A, Cabling ML, Lobo T et al (2016) Behavioral interventions to enhance adherence to hormone therapy in breast cancer survivors: a systematic literature review. Clin Breast Cancer 16(247–255):e3. https://doi.org/10.1016/j.clbc.2016.03.006

    Google Scholar 

Download references

Acknowledgements

We would like to thank all patients, pharmacists and oncologists of the IRFC-FC participating in this study. We also thank Ms Pamela Albert for English assistance in the correction of the manuscript.

Funding

No sources of funding were used to assist in the preparation of this article.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Virginie Nerich.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest related to the content of this manuscript.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Pourcelot, C., Orillard, E., Nallet, G. et al. Adjuvant hormonal therapy for early breast cancer: an epidemiologic study of medication adherence. Breast Cancer Res Treat 169, 153–162 (2018). https://doi.org/10.1007/s10549-018-4676-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-018-4676-3

Keywords

  • Adjuvant hormonal therapy
  • Aromatase inhibitors
  • Breast cancer
  • Medication adherence
  • Tamoxifen