Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ASCO Annual Meeting 2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

2024 ASCO Annual Meeting

Keep up to date with all the top stories and latest evidence with our hub page, including official congress videos and expert takeaways.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2023

Open Access 01-12-2023 | Breast Cancer | Research

Importance of endocrine treatment adherence and persistence in breast cancer survivorship: a systematic review

Authors: Finn Magnus Eliassen, Vibeke Blåfjelldal, Thomas Helland, Cathrine Fonnesbech Hjorth, Kari Hølland, Lise Lode, Bjørn-Erik Bertelsen, Emiel A. M. Janssen, Gunnar Mellgren, Jan Terje Kvaløy, Håvard Søiland, Tone Hoel Lende

Published in: BMC Cancer | Issue 1/2023

Login to get access

Abstract

Purpose

Adjuvant endocrine treatment is essential for treating luminal subtypes of breast cancer, which constitute 75% of all breast malignancies. However, the detrimental side effects of treatment make it difficult for many patients to complete the guideline-required treatment. Such non-adherence may jeopardize the lifesaving ability of anti-estrogen therapy. In this systematic review, we aimed to assess the consequences of non-adherence and non-persistence from available studies meeting strict statistical and clinical criteria.

Methods

A systematic literature search was performed using several databases, yielding identification of 2,026 studies. After strict selection, 14 studies were eligible for systematic review. The review included studies that examined endocrine treatment non-adherence (patients not taking treatment as prescribed) or non-persistence (patients stopping treatment prematurely), in terms of the effects on event-free survival or overall survival among women with non-metastatic breast cancer.

Results

We identified 10 studies measuring the effects of endocrine treatment non-adherence and non-persistence on event-free survival. Of these studies, seven showed significantly poorer survival for the non-adherent or non-persistent patient groups, with hazard ratios (HRs) ranging from 1.39 (95% CI, 1.07 to 1.53) to 2.44 (95% CI, 1.89 to 3.14). We identified nine studies measuring the effects of endocrine treatment non-adherence and non-persistence on overall survival. Of these studies, seven demonstrated significantly reduced overall survival in the groups with non-adherence and non-persistence, with HRs ranging from 1.26 (95% CI, 1.11 to 1.43) to 2.18 (95% CI, 1.99 to 2.39).

Conclusion

The present systematic review demonstrates that non-adherence and non-persistence to endocrine treatment negatively affect event-free and overall survival. Improved follow-up, with focus on adherence and persistence, is vital for improving health outcomes among patients with non-metastatic breast cancer.
Literature
1.
2.
3.
Ferlay J, Colombet M, Soerjomataram I, et al. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries and 25 major cancers in 2018. Eur J Cancer. 2018;103:356–87.PubMedCrossRef
4.
Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49.PubMedCrossRef
5.
Torre LA, Islami F, Siegel RL, et al. Global Cancer in Women: burden and trends. Cancer Epidemiol Biomarkers Prev. 2017;26:444–57.PubMedCrossRef
6.
Giaquinto AN, Sung H, Miller KD, et al: Breast Cancer Statistics, 2022. CA Cancer J Clin. 2022.
7.
Sorlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001;98:10869–74.PubMedPubMedCentralCrossRef
8.
Howlader N, Altekruse SF, Li CI, et al: US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J Natl Cancer Inst 2014;106.
9.
Earl H, Gray R, Kerr D, et al. The optimal duration of adjuvant tamoxifen treatment for breast cancer remains uncertain: randomize into aTTom. Clin Oncol (R Coll Radiol). 1997;9:141–3.PubMedCrossRef
10.
11.
Breast International Group 1–98 Collaborative G, Thurlimann B, Keshaviah A, et al: A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med 2005;353:2747–57.
12.
Early Breast Cancer Trialists' Collaborative G: Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005;365:1687–717.
13.
Davies C, Pan H, Godwin J, et al. 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. 2013;381:805–16.PubMedPubMedCentralCrossRef
14.
Early Breast Cancer Trialists' Collaborative G, Davies C, Godwin J, et al: Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet 2011;378:771–84.
15.
Cramer JA, Roy A, Burrell A, et al. Medication compliance and persistence: terminology and definitions. Value Health. 2008;11:44–7.PubMedCrossRef
16.
Karve S, Cleves MA, Helm M, et al. Good and poor adherence: optimal cut-point for adherence measures using administrative claims data. Curr Med Res Opin. 2009;25:2303–10.PubMedCrossRef
17.
18.
Toivonen KI, Williamson TM, Carlson LE, et al: Potentially modifiable factors associated with adherence to adjuvant endocrine therapy among breast cancer survivors: a systematic review. Cancers (Basel) 2020;13.
19.
Hsieh KP, Chen LC, Cheung KL, et al. Interruption and non-adherence to long-term adjuvant hormone therapy is associated with adverse survival outcome of breast cancer women–an Asian population-based study. PLoS ONE. 2014;9: e87027.PubMedPubMedCentralCrossRef
20.
Weaver KE, Camacho F, Hwang W, et al. Adherence to adjuvant hormonal therapy and its relationship to breast cancer recurrence and survival among low-income women. Am J Clin Oncol. 2013;36:181–7.PubMedPubMedCentralCrossRef
21.
Murphy CC, Bartholomew LK, Carpentier MY, et al. Adherence to adjuvant hormonal therapy among breast cancer survivors in clinical practice: a systematic review. Breast Cancer Res Treat. 2012;134:459–78.PubMedPubMedCentralCrossRef
22.
Oberguggenberger AS, Sztankay M, Beer B, et al. Adherence evaluation of endocrine treatment in breast cancer: methodological aspects. BMC Cancer. 2012;12:474.PubMedPubMedCentralCrossRef
23.
24.
Makubate B, Donnan PT, Dewar JA, et al. Cohort study of adherence to adjuvant endocrine therapy, breast cancer recurrence and mortality. Br J Cancer. 2013;108:1515–24.PubMedPubMedCentralCrossRef
25.
26.
27.
28.
Dezentje VO, van Blijderveen NJ, Gelderblom H, et al. Effect of concomitant CYP2D6 inhibitor use and tamoxifen adherence on breast cancer recurrence in early-stage breast cancer. J Clin Oncol. 2010;28:2423–9.PubMedCrossRef
29.
Hershman DL, Shao T, Kushi LH, 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;126:529–37.PubMedCrossRef
30.
Ejlertsen B, Jensen MB, Mouridsen HT, et al. Excess mortality in postmenopausal high-risk women who only receive adjuvant endocrine therapy for estrogen receptor positive breast cancer. Acta Oncol. 2014;53:174–85.PubMedCrossRef
31.
Chirgwin JH, Giobbie-Hurder A, Coates AS, et al. Treatment adherence and its impact on disease-free survival in the breast international group 1–98 trial of tamoxifen and letrozole, alone and in sequence. J Clin Oncol. 2016;34:2452–9.PubMedPubMedCentralCrossRef
32.
Gao P, You L, Wu D, et al. Adherence to endocrine therapy among Chinese patients with breast cancer: current status and recommendations for improvement. Patient Prefer Adherence. 2018;12:887–97.PubMedPubMedCentralCrossRef
33.
Font R, Espinas JA, Barnadas A, 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;175:733–40.PubMedCrossRef
34.
Pistilli B, Paci A, Ferreira AR, et al. Serum detection of nonadherence to adjuvant tamoxifen and breast cancer recurrence risk. J Clin Oncol. 2020;38:2762–72.PubMedPubMedCentralCrossRef
35.
de Brito C, Portela MC, de Vasconcellos MT. Health care factors associated with survival among women with breast cancer on hormone therapy in Rio de Janeiro, Brazil, 2004–2010. Rev Panam Salud Publica. 2016;39:358–65.PubMed
36.
Lao C, Lawrenson R, Edwards M, et al. Treatment and survival of Asian women diagnosed with breast cancer in New Zealand. Breast Cancer Res Treat. 2019;177:497–505.PubMedCrossRef
37.
Seneviratne S, Campbell I, Scott N, et al. Adherence to adjuvant endocrine therapy: is it a factor for ethnic differences in breast cancer outcomes in New Zealand? Breast. 2015;24:62–7.PubMedCrossRef
38.
Winn AN, Dusetzina SB. The association between trajectories of endocrine therapy adherence and mortality among women with breast cancer. Pharmacoepidemiol Drug Saf. 2016;25:953–9.PubMedCrossRef
39.
Lee Y, Park YR, Lee JS, et al. Prescription refill gap of endocrine treatment from electronic medical records as a prognostic factor in breast cancer patients. J Breast Cancer. 2019;22:86–95.PubMedPubMedCentralCrossRef
40.
Xing P, Dong H, Liu Q, et al. Impact of persistence on survival of patients with breast cancer treated with endocrine therapy in Northeast China: a prospective study. Oncotarget. 2017;8:102499–510.PubMedPubMedCentralCrossRef
41.
Collin LJ, Cronin-Fenton DP, Ahern TP, et al. Early discontinuation of endocrine therapy and recurrence of breast cancer among premenopausal women. Clin Cancer Res. 2021;27:1421–8.PubMedCrossRef
42.
Inotai A, Agh T, Maris R, et al. Systematic review of real-world studies evaluating the impact of medication non-adherence to endocrine therapies on hard clinical endpoints in patients with non-metastatic breast cancer. Cancer Treat Rev. 2021;100: 102264.PubMedCrossRef
43.
Wagner LI, Zhao F, Goss PE, et al. Patient-reported predictors of early treatment discontinuation: treatment-related symptoms and health-related quality of life among postmenopausal women with primary breast cancer randomized to anastrozole or exemestane on NCIC Clinical Trials Group (CCTG) MA.27 (E1Z03). Breast Cancer Res Treat. 2018;169:537–48.PubMedPubMedCentralCrossRef
44.
Condorelli R, Vaz-Luis I. Managing side effects in adjuvant endocrine therapy for breast cancer. Expert Rev Anticancer Ther. 2018;18:1101–12.PubMedCrossRef
45.
Helland T, Henne N, Bifulco E, et al. Serum concentrations of active tamoxifen metabolites predict long-term survival in adjuvantly treated breast cancer patients. Breast Cancer Res. 2017;19:125.PubMedPubMedCentralCrossRef
46.
Paranjpe R, John G, Trivedi M, et al. Identifying adherence barriers to oral endocrine therapy among breast cancer survivors. Breast Cancer Res Treat. 2019;174:297–305.PubMedCrossRef
47.
48.
Fleming L, Agnew S, Peddie N, et al. The impact of medication side effects on adherence and persistence to hormone therapy in breast cancer survivors: a quantitative systematic review. Breast. 2022;64:63–84.PubMedPubMedCentralCrossRef
49.
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:e303–13.PubMedCrossRef
50.
Cuzick J, Sestak I, Cella D, et al. Treatment-emergent endocrine symptoms and the risk of breast cancer recurrence: a retrospective analysis of the ATAC trial. Lancet Oncol. 2008;9:1143–8.PubMedCrossRef
51.
Mortimer JE, Flatt SW, Parker BA, et al. Tamoxifen, hot flashes and recurrence in breast cancer. Breast Cancer Res Treat. 2008;108:421–6.PubMedCrossRef
52.
Helland T, Hagen KB, Haugstoyl ME, et al. Drug monitoring of tamoxifen metabolites predicts vaginal dryness and verifies a low discontinuation rate from the Norwegian Prescription Database. Breast Cancer Res Treat. 2019;177:185–95.PubMedCrossRef
53.
Helland T, Naume B, Hustad S, et al. Low Z-4OHtam concentrations are associated with adverse clinical outcome among early stage premenopausal breast cancer patients treated with adjuvant tamoxifen. Mol Oncol. 2021;15:957–67.PubMedCrossRef
54.
Ruhstaller T, Giobbie-Hurder A, Colleoni M, et al. Adjuvant letrozole and tamoxifen alone or sequentially for postmenopausal women with hormone receptor-positive breast cancer: long-term follow-up of the BIG 1–98 Trial. J Clin Oncol. 2019;37:105–14.PubMedCrossRef
55.
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.PubMedPubMedCentralCrossRef
56.
Roberts MC, Wheeler SB, Reeder-Hayes K. Racial/Ethnic and socioeconomic disparities in endocrine therapy adherence in breast cancer: a systematic review. Am J Public Health. 2015;105(Suppl 3):e4–15.PubMedPubMedCentralCrossRef
57.
Finitsis DJ, Vose BA, Mahalak JG, et al. Interventions to promote adherence to endocrine therapy among breast cancer survivors: a meta-analysis. Psychooncology. 2019;28:255–63.PubMedCrossRef
58.
Hjorth CF, Damkier P, Ejlertsen B, et al. Socioeconomic position and prognosis in premenopausal breast cancer: a population-based cohort study in Denmark. BMC Med. 2021;19:235.PubMedPubMedCentralCrossRef
59.
Li CI. Racial and ethnic disparities in breast cancer stage, treatment, and survival in the United States. Ethn Dis. 2005;15:S5-9.PubMed
60.
Garber MC, Nau DP, Erickson SR, et al. The concordance of self-report with other measures of medication adherence: a summary of the literature. Med Care. 2004;42:649–52.PubMedCrossRef
61.
Bertelsen BE, Viste K, Helland T, et al. Simultaneous quantification of aromatase inhibitors and estrogens in postmenopausal breast cancer patients. J Clin Endocrinol Metab. 2022;107:1368–74.PubMedCrossRef
Metadata
Title
Importance of endocrine treatment adherence and persistence in breast cancer survivorship: a systematic review
Authors
Finn Magnus Eliassen
Vibeke Blåfjelldal
Thomas Helland
Cathrine Fonnesbech Hjorth
Kari Hølland
Lise Lode
Bjørn-Erik Bertelsen
Emiel A. M. Janssen
Gunnar Mellgren
Jan Terje Kvaløy
Håvard Søiland
Tone Hoel Lende
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-023-11122-8

Other articles of this Issue 1/2023

BMC Cancer 1/2023 Go to the issue

Research

Knockdown of SLC39A14 inhibits glioma progression by promoting erastin-induced ferroptosis SLC39A14 knockdown inhibits glioma progression

Research

Mini-open compared with the trans-tubular approach in patients with spinal metastases underwent decompression surgery---a retrospective cohort study

Research

Dynamic changes of phenotype and function of natural killer cells in peripheral blood before and after thermal ablation of hepatitis B associated hepatocellular carcinoma and their correlation with tumor recurrence

Research

Analysis of stromal PDGFR-β and α-SMA expression and their clinical relevance in brain metastases of breast cancer patients

Research

Risk of cervical intraepithelial neoplasia grade 2 or worse in women aged ≥ 69 referred to colposcopy due to an HPV-positive screening test

Research

Neoadjuvant chemotherapy with weekly cisplatin and paclitaxel followed by chemoradiation for locally advanced cervical cancer
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits