RSS-Feed abonnieren
PDF herunterladen
DOI: 10.1055/a-2687-9258
High Adherence to Adjuvant Endocrine Therapy Improves Outcome in Early Breast Cancer – Results from a Large Real-World Claims Data Analysis in Germany
Eine hohe Adhärenz zur adjuvanten endokrinen Therapie verbessert das Outcome bei frühem Brustkrebs – Ergebnisse aus einer großen Real-World-Datenanalyse in DeutschlandGefördert durch: AOK Baden-Württemberg
Abstract
In hormone-receptor positive (HR+) early breast cancer (EBC), adjuvant endocrine therapy
(ET) significantly reduces recurrence and mortality. A common means of estimating
therapy adherence is to use patient-reported outcome measures. Yet, this method is
inaccurate due to social-desirability bias. We therefore aimed to analyze adherence
to ET over the first five years of treatment by using claims data from a large health
insurance provider in Germany (AOK Baden-Wuerttemberg).
Female patients diagnosed with HR+ EBC who received inpatient treatment and breast
cancer surgery between 1 July 2010 and 31 December 2019 were included in the analysis.
Adherence to ET was defined as the ratio between the sum of the number of pills from
filled prescriptions and the duration of ET in days (from the start of the first prescription
after completing surgery and chemotherapy). ET use was observed over five years. Low
adherence was defined as a ratio smaller than 0.8 and high adherence as a ratio larger
than or equal to 0.8. Distant recurrence-free survival (DRFS) was calculated from
the day of the first diagnosis of EBC until onset of distant recurrence. Overall survival
(OS) was defined as the period between first diagnosis of EBC until death of any cause.
In total, 16642 patients with EBC were included. Of these patients, 4303 (86%) showed
high adherence to ET in the first year after initiating treatment. After five years,
high adherence persisted in 68% of patients. Continuous high adherence to ET had a
significant impact on DRFS (HR: 0.66; 95% CI: 0.58–0.76, p > 0.0001) and OS (HR 0.52,
95% CI: 0.47–0.57, p < 0.0001).
In conclusion, adherence to ET is an independent risk factor that significantly influences
DRFS and OS. Further real-world studies should explore the factors contributing to
treatment discontinuation and evaluate prospective strategies to enhance adherence.
Zusammenfassung
Bei Patientinnen mit hormonrezeptorpositivem (HR+) frühem Brustkrebs (EBC) reduziert
die adjuvante endokrine Therapie (ET) signifikant das Rezidiv- und Mortalitätsrisiko.
Eine gängige Methode zur Messung der Therapieadhärenz ist die direkte Befragung der
Patientinnen, die jedoch ungenau sein kann. Daher war das Ziel dieser Studie, die
Adhärenz zur ET über die ersten 5 Behandlungsjahre mithilfe von Abrechnungsdaten eines
großen deutschen Krankenversicherers (AOK Baden-Württemberg) zu analysieren.
In die Analyse wurden weibliche Patientinnen mit der Diagnose HR+ EBC einbezogen,
die zwischen dem 1. Juli 2010 und dem 31. Dezember 2019 eine stationäre Behandlung
und eine Brustkrebsoperation erhielten. Die Adhärenz zur ET wurde als das Verhältnis
zwischen der Summe der Tablettenanzahl aus eingelösten Rezepten und der Therapiedauer
in Tagen definiert (beginnend mit der ersten Verschreibung nach Abschluss der Operation
und Chemotherapie). Die Nutzung der ET wurde über 5 Jahre beobachtet. Eine niedrige
Adhärenz lag bei einem Verhältnis von weniger als 0,8 vor, während eine hohe Adhärenz
einem Verhältnis von 0,8 oder mehr entsprach. Das fernrezidivfreie Überleben (DRFS)
wurde vom Tag der Erstdiagnose des EBC bis zum Auftreten eines Fernrezidivs berechnet.
Das Gesamtüberleben (OS) wurde als der Zeitraum zwischen der Erstdiagnose und dem
Tod jeglicher Ursache definiert.
Insgesamt wurden 16642 Patientinnen mit EBC in die Studie eingeschlossen. Davon zeigten
4303 (86%) im 1. Jahr nach Therapiebeginn eine hohe Adhärenz zur ET. Nach 5 Jahren
hielten 68% der Patientinnen eine hohe Adhärenz aufrecht. Eine kontinuierlich hohe
Adhärenz zur ET hatte einen signifikanten Einfluss auf das DRFS (HR: 0,66; 95%-KI:
0,58–0,76, p > 0,0001) und das OS (HR 0,52, 95%-KI: 0,47–0,57, p < 0,0001).
Zusammenfassend ist festzuhalten, dass die Adhärenz zur ET ein unabhängiger Risikofaktor
ist, der DRFS und OS signifikant beeinflusst. Weitere Real-World-Analysen sollten
die Faktoren, die zum Therapieabbruch beitragen, untersuchen und prospektive Strategien
zur Verbesserung der Adhärenz evaluieren.
-
This is the first German claims analysis to show the impact of adherence to endocrine therapy on recurrence and mortality.
-
High adherence to endocrine therapy (ET) improves survival in early breast cancer.
-
68% maintained high adherence to ET after five years of treatment.
-
Low adherence significantly increased risks of recurrence and mortality.
-
Older age and higher comorbidities negatively impacted ET adherence.
Publikationsverlauf
Eingereicht: 20. Juli 2025
Angenommen nach Revision: 17. August 2025
Artikel online veröffentlicht:
10. September 2025
© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).
Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
-
References
- 1 Robert Koch-Institut. Krebs in Deutschland für 2017/2018. 2021 Zugriff am 09. September 2025 unter: https://www.krebsdaten.de/Krebs/DE/Content/Publikationen/Krebs_in_Deutschland/kid_2021/krebs_in_deutschland_2021.pdf?__blob=publicationFile
- 2 Jemal A, Center MM, DeSantis C. et al. Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev 2010; 19: 1893-1907
- 3 Cardoso F, Kyriakides S, Ohno S. et al. Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Ann Oncol 2019; 30: 1194-1220
- 4 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 randomised trials. Lancet 2005; 365: 1687-1717
- 5 Peto R, Davies C, Godwin J. et al. Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet 2012; 379: 432-444
- 6 Francis PA, Pagani O, Fleming GF. et al. Tailoring Adjuvant Endocrine Therapy for Premenopausal Breast Cancer. N Engl J Med 2018; 379: 122-137
- 7 Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Aromatase inhibitors versus tamoxifen in premenopausal women with oestrogen receptor-positive early-stage breast cancer treated with ovarian suppression: a patient-level meta-analysis of 7030 women from four randomised trials. Lancet Oncol 2022; 23: 382-392
- 8 Franzoi MA, Agostinetto E, Perachino M. et al. Evidence-based approaches for the management of side-effects of adjuvant endocrine therapy in patients with breast cancer. Lancet Oncol 2021; 22: e303-e313
- 9 Murphy CT, Li T, Wang LS. et al. Comparison of Adjuvant Radiation Therapy Alone Versus Radiation Therapy and Endocrine Therapy in Elderly Women With Early-Stage, Hormone Receptor-Positive Breast Cancer Treated With Breast-Conserving Surgery. Clin Breast Cancer 2015; 15: 381-389
- 10 Yussof I, Mohd Tahir NA, Hatah E. et al. Factors influencing five-year adherence to adjuvant endocrine therapy in breast cancer patients: A systematic review. Breast 2022; 62: 22-35
- 11 Cramer JA, Roy A, Burrell A. et al. Medication compliance and persistence: terminology and definitions. Value Health 2008; 11: 44-47
- 12 Neiman AB, Ruppar T, Ho M. et al. CDC Grand Rounds: Improving Medication Adherence for Chronic Disease Management – Innovations and Opportunities. MMWR Morb Mortal Wkly Rep 2017; 66: 1248-1251
- 13 Mistry N, Keepanasseril A, Wilczynski NL. et al. Technology-mediated interventions for enhancing medication adherence. J Am Med Inform Assoc 2015; 22: e177-e193
- 14 Nieuwlaat R, Wilczynski N, Navarro T. et al. Interventions for enhancing medication adherence. Cochrane Database Syst Rev 2014; (11) CD000011
- 15 Brown MT, Bussell JK. Medication adherence: WHO cares?. Mayo Clin Proc 2011; 86: 304-314
- 16 Lam WY, Fresco P. Medication Adherence Measures: An Overview. Biomed Res Int 2015; 2015: 217047
- 17 Font R, Espinas JA, Gil-Gil M. 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: 1249-1256
- 18 Pistilli B, Paci A, Ferreira AR. et al. Serum Detection of Nonadherence to Adjuvant Tamoxifen and Breast Cancer Recurrence Risk. J Clin Oncol 2020; 38: 2762-2772
- 19 He W, Fang F, Varnum C. et al. Predictors of Discontinuation of Adjuvant Hormone Therapy in Patients With Breast Cancer. J Clin Oncol 2015; 33: 2262-2269
- 20 He W, Eriksson M, Eliasson E. et al. CYP2D6 genotype predicts tamoxifen discontinuation and drug response: a secondary analysis of the KARISMA trial. Ann Oncol 2021; 32: 1286-1293
- 21 Dannehl D, von Au A, Engler T. et al. Implementation and Evaluation of a Breast Cancer Disease Model Using Real-World Claims Data in Germany from 2010 to 2020. Cancers (Basel) 2024; 16: 1490
- 22 Scholz AS, von Au A, Gutsfeld R. et al. Adverse Obstetric Outcomes after Breast Cancer Diagnosis: An Observational Database Study in Germany. Cancers (Basel) 2024; 16: 1490
- 23 von Au A, Dannehl D, Dijkstra TMH. et al. Breast Cancer and Mental Health: Incidence and Influencing Factors-A Claims Data Analysis from Germany. Cancers (Basel) 2024; 16: 3688
- 24 Castelo-Branco L, Pellat A, Martins-Branco D. et al. ESMO Guidance for Reporting Oncology real-World evidence (GROW). Ann Oncol 2023; 34: 1097-1112
- 25 Bosco-Lévy P, Jové J, Robinson P. et al. Persistence to 5-year hormonal breast cancer therapy: a French national population-based study. Br J Cancer 2016; 115: 912-919
- 26 Cavazza M, Banks H, Ercolanoni M. et al. Factors influencing adherence to adjuvant endocrine therapy in breast cancer-treated women: using real-world data to inform a switch from acute to chronic disease management. Breast Cancer Res Treat 2020; 183: 189-199
- 27 Emerson MA, Achacoso NS, Benefield HC. et al. Initiation and adherence to adjuvant endocrine therapy among urban, insured American Indian/Alaska Native breast cancer survivors. Cancer 2021; 127: 1847-1856
- 28 Guedes JBR, Guerra MR, Alvim MM. et al. Factors associated with adherence and persistence to hormonal therapy in women with breast cancer. Rev Bras Epidemiol 2017; 20: 636-649
- 29 Lailler G, Memoli V, Le Bihan Benjamin C. et al. Five-Year Adjuvant Endocrine Therapy Adherence Trajectories Among Women With Breast Cancer: A Nationwide French Study Using Administrative Data. Clin Breast Cancer 2021; 21: e415-e426
- 30 Lambert-Côté L, Bouhnik AD, Bendiane MK. et al. Adherence trajectories of adjuvant endocrine therapy in the five years after its initiation among women with non-metastatic breast cancer: a cohort study using administrative databases. Breast Cancer Res Treat 2020; 180: 777-790
- 31 McCowan C, Shearer J, Donnan PT. et al. Cohort study examining tamoxifen adherence and its relationship to mortality in women with breast cancer. Br J Cancer 2008; 99: 1763-1768
- 32 Chlebowski RT, Kim J, Haque R. Adherence to endocrine therapy in breast cancer adjuvant and prevention settings. Cancer Prev Res (Phila) 2014; 7: 378-387
- 33 Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet 2015; 386: 1341-1352
- 34 World Health Organization. Adherence to long-term therapies: evidence for action. Geneva: World Health Organization; 2003. Zugriff am 09. September 2025 unter: https://iris.who.int/handle/10665/42682
- 35 Osterberg L, Blaschke T. Adherence to medication. N Engl J Med 2005; 353: 487-497
- 36 Checchi KD, Huybrechts KF, Avorn J. et al. Electronic medication packaging devices and medication adherence: a systematic review. JAMA 2014; 312: 1237-1247
- 37 Janni W, Kolberg HC, Hartkopf AD. et al. Update Breast Cancer 2024 Part 2–Patients with Early Stage Breast Cancer. Geburtshilfe Frauenheilkd 2025; 85: 493-506
- 38 Dannehl D, Volmer LL, Weiss M. et al. Feasibility of Adjuvant Treatment with Abemaciclib-Real-World Data from a Large German Breast Center. J Pers Med 2022; 12: 382
- 39 Schäffler H, Mergel F, Pfister K. et al. The Clinical Relevance of the NATALEE Study: Application of the NATALEE Criteria to a Real-World Cohort from Two Large German Breast Cancer Centers. Int J Mol Sci 2023; 24: 16366
- 40 Untch M, Banys-Paluchowski M, Brucker SY. et al. Treatment of Patients with Early Breast Cancer: 19th St. Gallen International Breast Cancer Consensus Discussed against the Background of German Treatment Recommendations. Geburtshilfe Frauenheilkd 2025; 85: 677-693