Skip to main content
SpringerLink
Log in

Adherence to Adjuvant Endocrine Therapy and Survival Among Older Women with Early-Stage Hormone Receptor-Positive Breast Cancer

  • Original Research Article
  • Published:
Clinical Drug Investigation Aims and scope Submit manuscript

Abstract

Background and Objective

Although improving adherence to adjuvant endocrine therapies (AETs) is critical to ensure better patient outcomes, the evidence is still lacking on differences in 5-year AET adherence trajectories. This study aimed to estimate the time trend of adherence by the type of individual AET and the association of adherence to AETs with overall survival among older women with hormone receptor-positive breast cancer.

Methods

This study used the Surveillance, Epidemiology, and End Results-Medicare database 2006–2016. We included women aged ≥ 65 years with newly diagnosed hormone receptor-positive breast cancer and who had initiated AET (anastrozole, letrozole, exemestane, or tamoxifen). Adherence to AETs was defined as the proportion of days covered that was calculated for the follow-up period (5 years). The overall survival time was defined as the time from the date of AET initiation to death. The linear mixed models with repeated measures were used to estimate the changes in adherence to AETs. The Cox proportional hazard model was used to assess the relationships (hazard ratio [HR] and 95% confidence interval [CI]) between adherence to AETs and death.

Results

A total of 11,617 patients were included. Anastrozole was the most commonly used (n = 6,908), followed by letrozole (n = 2,586), tamoxifen (n = 1,750), and exemestane (n = 373). The mean (standard deviation) of proportion of days covered for 5 years was 57.4 (34.6), indicating the highest proportion of days covered in the anastrozole group [61.1 (34.1)] and the lowest proportion of days covered in the exemestane group [44.0 (35.1)]. Overall, adherence to AET decreased over the 5-year follow-up period in all AET groups, but the decrease in the tamoxifen group was steeper (42.3% decreased) compared with other AETs. Anastrozole, letrozole, and exemestane groups were associated with a lower risk of death compared with the tamoxifen group (HR = 0.80, 95% CI 0.71–0.89 for anastrozole; HR = 0.82, 95% CI 0.72–0.93 for letrozole; HR = 0.82, 95% CI 0.63–1.07 for exemestane).

Conclusions

Patients who initiated with tamoxifen had a steeper decrease in adherence over the 5 years compared with anastrozole, letrozole, and exemestane groups. Furthermore, higher adherence was associated with a decreased risk of mortality. Physicians should be cognizant of decreasing adherence over time and choose effective treatment options with minimal side-effect profiles to better support adherence by patients with breast cancer.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J Clin. 2021;71(1):7–33.

    Article  PubMed  Google Scholar 

  2. National Cancer Institute. Cancer stat facts: female breast cancer subtypes. https://seer.cancer.gov/statfacts/html/breast-subtypes.html. Accessed 13 Jan 2022.

  3. National Cancer Institute. Cancer stat facts: female breast cancer. https://seer.cancer.gov/statfacts/html/breast.html. Accessed 13 Jan 2022.

  4. Cardoso F, Kyriakides S, Ohno S, Penault-Llorca F, Poortmans P, Rubio IT, et al. Early breast cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2019;30(10):1674.

    Article  CAS  PubMed  Google Scholar 

  5. Burstein HJ, Temin S, Anderson H, Buchholz TA, Davidson NE, Gelmon KE, et al. Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: American Society of Clinical Oncology clinical practice guideline focused update. J Clin Oncol. 2014;32(21):2255–69.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Aydiner A. Meta-analysis of breast cancer outcome and toxicity in adjuvant trials of aromatase inhibitors in postmenopausal women. Breast. 2013;22(2):121–9.

    Article  PubMed  Google Scholar 

  7. Early Breast Cancer Trialists’ Collaborative Group. Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet. 2015;386(10001):1341–52.

    Article  Google Scholar 

  8. Goss PE, Ingle JN, Pritchard KI, Ellis MJ, Sledge GW, Budd GT, et al. Exemestane versus anastrozole in postmenopausal women with early breast cancer: NCIC CTG MA.27—a randomized controlled phase III trial. J Clin Oncol. 2013;31(11):1398–404.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Smith I, Yardley D, Burris H, De Boer R, Amadori D, McIntyre K, et al. Comparative efficacy and safety of adjuvant letrozole versus anastrozole in postmenopausal patients with hormone receptor-positive, node-positive early breast cancer: final results of the randomized phase III Femara Versus Anastrozole Clinical Evaluation (FACE) Trial. J Clin Oncol. 2017;35(10):1041–8.

    Article  CAS  PubMed  Google Scholar 

  10. Peddie N, Agnew S, Crawford M, Dixon D, MacPherson I, Fleming L. The impact of medication side effects on adherence and persistence to hormone therapy in breast cancer survivors: a qualitative systematic review and thematic synthesis. Breast. 2021;58:147–59.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Lambert LK, Balneaves LG, Howard AF, Chia SK, Gotay CC. Understanding adjuvant endocrine therapy persistence in breast cancer survivors. BMC Cancer. 2018;18(1):732.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Hershman DL, Kushi LH, Shao T, Buono D, Kershenbaum A, Tsai WY, et al. Early discontinuation and nonadherence to adjuvant hormonal therapy in a cohort of 8,769 early-stage breast cancer patients. J Clin Oncol. 2010;28(27):4120–8.

    Article  PubMed  PubMed Central  Google Scholar 

  13. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. 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 

  15. Huiart L, Bouhnik AD, Rey D, Rousseau F, Retornaz F, Meresse M, et al. Complementary or alternative medicine as possible determinant of decreased persistence to aromatase inhibitor therapy among older women with non-metastatic breast cancer. PLoS One. 2013;8(12): e81677.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Mohamed KEH, Elamin A. Adherence to endocrine therapy and its relation to disease-free survival among breast cancer patients visiting an out-patient clinic at Khartoum Oncology Hospital, Sudan. J Eval Clin Pract. 2020;26(6):1731–43.

    Article  PubMed  Google Scholar 

  17. Font R, Espinas JA, Barnadas A, Izquierdo A, Galceran J, Saladie F, et al. Influence of adherence to adjuvant endocrine therapy on disease-free and overall survival: a population-based study in Catalonia, Spain. Breast Cancer Res Treat. 2019;175(3):733–40.

    Article  CAS  PubMed  Google Scholar 

  18. SEER-Medicare: brief description of the SEER-Medicare database: National Cancer Institute (NCI). https://healthcaredelivery.cancer.gov/seermedicare/overview/. Accessed 2 Dec 2019.

  19. Overview of the SEER Program: National Cancer Institute (NCI). https://seer.cancer.gov/about/overview.html. Accessed 2 Dec 2022.

  20. Galizzi MM, Ghislandi S, Miraldo M. Effects of reference pricing in pharmaceutical markets: a review. Pharmacoeconomics. 2011;29(1):17–33.

    Article  PubMed  Google Scholar 

  21. SEER-Medicare: Medicare claims files: National Cancer Institute (NCI). https://healthcaredelivery.cancer.gov/seermedicare/medicare/claims.html. Accessed 2 Dec 2022.

  22. Meneveau MO, Keim-Malpass J, Camacho TF, Anderson RT, Showalter SL. Predicting adjuvant endocrine therapy initiation and adherence among older women with early-stage breast cancer. Breast Cancer Res Treat. 2020;184(3):805–16.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Yang J, Neugut AI, Wright JD, Accordino M, Hershman DL. Nonadherence to oral medications for chronic conditions in breast cancer survivors. J Oncol Pract. 2016;12(8):e800–9.

    Article  PubMed  Google Scholar 

  24. Farias AJ, Du XL. Association between out-of-pocket costs, race/ethnicity, and adjuvant endocrine therapy adherence among Medicare patients with breast cancer. J Clin Oncol. 2017;35(1):86–95.

    Article  PubMed  Google Scholar 

  25. Pharmacy Quality Alliance. Adherence; 2022. https://www.pqaalliance.org/adherence-measures. Accessed 15 Jan 2023.

  26. National Cancer Institute. NCI comorbidity index overview. https://healthcaredelivery.cancer.gov/seermedicare/considerations/comorbidity.html. Accessed 13 Jan 2022.

  27. Makubate B, Donnan PT, Dewar JA, Thompson AM, McCowan C. Cohort study of adherence to adjuvant endocrine therapy, breast cancer recurrence and mortality. Br J Cancer. 2013;108(7):1515–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. 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 

  29. Verbrugghe M, Verhaeghe S, Decoene E, De Baere S, Vandendorpe B, Van Hecke A. Factors influencing the process of medication (non-)adherence and (non-)persistence in breast cancer patients with adjuvant antihormonal therapy: a qualitative study. Eur J Cancer Care (Engl). 2017. https://doi.org/10.1111/ecc.12339.

    Article  PubMed  Google Scholar 

  30. Bourmaud A, Henin E, Tinquaut F, Regnier V, Hamant C, Colomban O, et al. Adherence to oral anticancer chemotherapy: what influences patients’ over or non-adherence? Analysis of the OCTO study through quantitative-qualitative methods. BMC Res Notes. 2015;8:291.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Ruddy K, Mayer E, Partridge A. Patient adherence and persistence with oral anticancer treatment. CA Cancer J Clin. 2009;59(1):56–66.

    Article  PubMed  Google Scholar 

  32. Hansen RA, Kim MM, Song L, Tu W, Wu J, Murray MD. Comparison of methods to assess medication adherence and classify nonadherence. Ann Pharmacother. 2009;43(3):413–22.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. College of Pharmacy, The University of Texas at Austin, 2400 Inner Campus Drive, Austin, TX, 78705, USA

    Chanhyun Park, Ji-Haeng Heo & Sola Han

  2. College of Natural Sciences, The University of Texas at Austin, Austin, TX, USA

    Sanica Mehta

  3. Dell Medical School, The University of Texas at Austin, Austin, TX, USA

    Jennifer C. Spencer

Authors
  1. Chanhyun Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ji-Haeng Heo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sanica Mehta
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sola Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jennifer C. Spencer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chanhyun Park.

Ethics declarations

Funding

This article was supported by IRG-21-135-01-IRG from the American Cancer Society.

Conflict of interest

Chanhyun Park, Ji-Haeng Heo, Sanica Mehta, Sola Han, and Jennifer C. Spencer have no conflicts of interest that are directly relevant to the content of this article.

Ethics approval

As a secondary data analysis of the de-identified data, we obtained approval from The University of Texas at Austin Institutional Review Board to conduct this study.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Data availability

Access to the data that support the findings of this study (SEER-Medicare) is strictly limited to members of the research team who signed the Data Use Agreement.

Code availability

Not applicable.

Author contributions

CP and JHH led the study conception and performed the data analysis. CP and SM drafted the manuscript. CP, JHH, SH, and JCS took part in revising and critically reviewing the manuscript. All authors read and approved the final manuscript.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 307 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Park, C., Heo, JH., Mehta, S. et al. Adherence to Adjuvant Endocrine Therapy and Survival Among Older Women with Early-Stage Hormone Receptor-Positive Breast Cancer. Clin Drug Investig 43, 167–176 (2023). https://doi.org/10.1007/s40261-023-01247-w

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40261-023-01247-w

Search

Navigation