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Endocrine treatment and incidence of relapse in women with oestrogen receptor-positive breast cancer in Europe: a population-based study

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

Endocrine therapy (ET) is the mainstream adjuvant treatment for ER-positive breast cancer (BC). We analysed 9293 ER-positive BC patients diagnosed in nine European countries in 2009–2013 to investigate how comorbidities at diagnosis, age, stage and subtype affected ET use over time, and relapse.

Methods

Adjusted odds ratios (ORs) and 95% confidence intervals (95%CIs) of receiving ET were estimated according to Charlson comorbidity, age, stage and subtype using logistic regression. The 2-year cumulative incidence and adjusted sub-hazard ratios (SHRs) of relapse were estimated using competing risk analysis, with all-cause death as the competing event. The z-test was used to assess differences in the proportion of patients receiving ET in 1996–1998 and 2009–2013.

Results

Ninety percent of the patients started adjuvant ET, range 96% (Belgium, Estonia, Slovenia, Spain)—75% (Switzerland). ORs of starting ET were lower for women aged > 75 years, with severe comorbidities, or luminal B HER2-positive cancer. The factors independently increasing the risk of relapse were: not receiving ET (SHR 2.26, 95%CI 1.02–5.03); severe comorbidity (SHR 1.94, 95%CI 1.06–3.55); luminal B, either HER2 negative (SHR 3.06, 95%CI 1.61–5.79) or positive (SHR 3.10, 95%CI 1.36–7.07); stage II (SHR 3.20, 95%CI 1.56–6.57) or stage III (SHR 7.41, 95%CI 3.48–15.73). ET use increased significantly but differently across countries from 51–85% in 1996–1998 to 86–96% in 2009–2013.

Conclusions

ER-positive BC patients in Europe are increasingly prescribed ET but between-country disparities persist. Older women and women with severe comorbidity less frequently receive ET. ET omission and severe comorbidity independently predict early disease relapse.

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Abbreviations

BC:

Breast cancer

CCI:

Charlson Comorbidity Index

CI:

Confidence interval

CR:

Cancer registry

ER:

Oestrogen receptor

ET:

Endocrine therapy

HER2:

Human epidermal growth factor receptor 2

HR:

High resolution

OR:

Odds ratio

SHR:

Sub-hazard ratio

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Acknowledgements

The authors would like to thank Camilla Amati and Kevin Smart for their help with the English, and the participating cancer registries for collecting and preparing the data as part of their essential role in cancer control.

European High Resolution Working Group on Breast: Belgium: L. Van Eycken, K. Henau (Belgian CR, Flanders); Estonia: K. Innos, M. Mägi (Estonia CR); France: F. Binder-Foucard, M. Velten, (Bas-Rhin CR); A.V. Guizard (Calvados general CR); P. Arveux (Côte d’Or gynaecologic CR); A.S. Woronoff (Doubs CR); B. Amadeo, G. Coureau (Gironde CR); E. Marrer, S. Boyer (Haut-Rhin CR); N. Léone (Haute-Vienne CR); B. Trétarre (Hérault CR); M. Colonna, P. Delafosse (Isère CR); V. Démaret, K. Ligier (Lille et sa région CR); S. Ayrault-Piault (Loire-Atlantique CR); S. Bara (Manche CR); G. Defossez (Poitou–Charentes CR); B. Lapotre-Ledoux (Somme CR); L. Daubisse-Marliac, P. Grosclaude (Tarn CR); A. Cowppli-Bony (Vendée CR); F Molinié (Loire-Atlantique/Vendée CR, FRANCIM);Germany: V. Babaev, A. Katalinic (Germany-Schleswig–Holstein CR); Italy: C. Amati, P. Baili, S. Bonfarnuzzo, E. Meneghini, P. Minicozzi, G. Moretti, M. Sant (Fondazione IRCCS Istituto Nazionale dei Tumori, Milan); Silvia Iacovacci, Susanna Busco (Latina CR); E. Marani, C. Casella, R. (Liguria CR, Ospedale Policlinico San Martino IRCCS); G. Carrozzi, C. Cirilli (Modena CR); R. Amodio, R. Cusimano (Palermo CR); C. Nicita, R. Tumino (Ragusa CR, ASP); F. Ferrari, L. Mangone (Reggio Emilia CR, IRCCS AUSL ASMN); F. Stracci, F. Bianconi (Umbria CR); P. Contiero, G. Tagliabue (Varese Province CR, Fondazione IRCCS Istituto Nazionale dei Tumori); Poland: L. Molong, J. Rachtan (Cracow CR); J. Janowski, A. Kubiak (Greater Poland CR); S. Góźdź, P. Macek (Kielce CR); M. Bielska-Lasota (National Institute of Public Health-NIH, Warsaw); J. Błaszczyk, K. Kępska (Lower Silesia CR, Wroclaw); Portugal: J. Bastos, B. Carrito (Central Portugal CR); M. J. Bento, C. Castro (Northern Portugal CR); A. Mayer-da-Silva, A. Miranda, (Southern Portugal CR); Slovenia: V. Zadnig (National CR), G. Plavc (Institute of Oncology Ljubljana); Spain: L. Gil Majuelo, N. Larrañaga (Basque Country CR, CIBERESP); C. Sabater, A. Torella (Castellón-Valencia CR); R. Marcos-Gragera, M. Puigdemont (Girona CR, CIBERESP, ICO,IDIBGI); E. Molina-Portillo, M. J. Sánchez-Pérez (Granada CR, EASP, CIBERESP, ibs.Granada); E. Ardanaz, M. Guevara (Navarra CR, CIBERESP, IdiSNa); J. Galceran, F. Saladié (Tarragona CR);Switzerland: C. Bouchardy, E. Fournier (Geneva CR, University of Geneva).

Funding

These results have been achieved within the framework of the call on “Translational research on tertiary prevention in cancer patients (TRANSCAN)” carried out by ERA-NET, with funding from: Ministero della Salute, Dipartimento della Sanità Pubblica e dell’Innovazione, Direzione Generale della Ricerca Sanitaria e Biomedica e della Vigilanza sugli Enti (MoH), Viale Giorgio Ribotta 5, Roma, Italy; Fonds voor Wetenschappelijk Onderzoek Vlaanderen, FWO (Research Foundation Flanders), Egmonstraat 5 B-1000 Brussels, Belgium; Institut National du Cancer (INCa), 52 avenue André Morizet, 92513 Boulogne Billancourt Cedex, France; Federal Ministry of Education and Research (BMBF), Heinrich-Konen-Str. 1, D-53227 Bonn, Germany; Narodowego Centrum Badań i Rozwoju (NCBR) ul. Nowogrodzka 47a, 00695 Warszawa Poland; Ministrstvo za izobraževanje, znanost in šport (Ministry of Education, Science and Sport, MIZS), Masarykova 16, 1000 Ljubljana, Slovenia; The Instituto de Salud Carlos III (ISCIII), C/Sinesio Delgado 4, 28029 Madrid, Spain (Grant No. AC14/00036); Fundación Bancaria Caixa d’Estalvis i Pensions de Barcelona, Plaza Weyler, 3, 07001 Palma, Spain. Andalusian Department of Health, Spain (Grant No. PI-0152/2017).

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Authors and Affiliations

  1. Analytical Epidemiology and Health Impact Unit, Research Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133, Milan, Italy

    Milena Sant, Elisabetta Meneghini & Pamela Minicozzi

  2. Portuguese Institute of Oncology Francisco Gentil (IPO Coimbra), Coimbra, Portugal

    Joana Bastos

  3. Epidemiology Unit, Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia, Reggio Emilia, Italy

    Paolo Giorgi Rossi

  4. Navarra Public Health Institute, Pamplona, Spain

    Marcela Guevara

  5. IdiSNA, Navarra Institute for Health Research, Pamplona, Spain

    Marcela Guevara

  6. CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain

    Marcela Guevara & Rafael Marcos-Gragera

  7. Department of Epidemiology and Biostatistics, National Institute for Health Development, Tallinn, Estonia

    Kaire Innos

  8. Institut für Sozialmedizin und Epidemiologie, Institut für Krebsepidemiologie e.V, Universität Lübeck, Lübeck, Germany

    Alexander Katalinic

  9. Public Health Division of Gipuzkoa, Biodonostia Health Research Institute, Ministry of Health of the Basque Government, San Sebastian, Spain

    Leire Gil Majuelo

  10. Epidemiology Unit and Girona Cancer Registry, Department of Health, Catalan Institute of Oncology (ICO), Girona, Spain

    Rafael Marcos-Gragera

  11. Geneva Cancer Registry, Global Health Institute, University of Geneva, Geneva, Switzerland

    Elisabetta Rapiti

  12. Castellon Cancer Registry-CISCV, Cancer Information System of Comunitat Valenciana (CIS-CV), Public Health Directorate General Health Departament, Valencia, Spain

    Ana Vizcaino

  13. Epidemiology and Cancer Registry, Institute of Oncology, Ljubljana, Slovenia

    Vesna Zadnik

  14. Loire-Atlantique/Vendée Cancer Registry, Nantes, France

    Florence Molinié

  15. SIRIC ILIAD INCa-DGOSInserm_12558, CHU Nantes, Nantes, France

    Florence Molinié

  16. French Network of Cancer Registries (FRANCIM), Toulouse, France

    Florence Molinié

  17. Cancer Survival Group, Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK

    Pamela Minicozzi

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  1. Milena Sant
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  2. Elisabetta Meneghini
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  7. Alexander Katalinic
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  8. Leire Gil Majuelo
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Consortia

the European High Resolution Working Group on breast cancer

  • L. Van Eycken
  • , K. Henau
  • , K. Innos
  • , M. Mägi
  • , F. Binder-Foucard
  • , M. Velten
  • , A. V. Guizard
  • , P. Arveux
  • , A. S. Woronoff
  • , B. Amadeo
  • , G. Coureau
  • , E. Marrer
  • , S. Boyer
  • , N. Léone
  • , B. Trétarre
  • , M. Colonna
  • , P. Delafosse
  • , V. Démaret
  • , K. Ligier
  • , S. Ayrault-Piault
  • , S. Bara
  • , G. Defossez
  • , B. Lapotre-Ledoux
  • , L. Daubisse-Marliac
  • , P. Grosclaude
  • , A. Cowppli-Bony
  • , F Molinié
  • , V. Babaev
  • , A. Katalinic
  • , C. Amati
  • , P. Baili
  • , S. Bonfarnuzzo
  • , E. Meneghini
  • , P. Minicozzi
  • , G. Moretti
  • , M. Sant
  • , Silvia Iacovacci
  • , Susanna Busco
  • , E. Marani
  • , C. Casella
  • , G. Carrozzi
  • , C. Cirilli
  • , R. Amodio
  • , R. Cusimano
  • , C. Nicita
  • , R. Tumino
  • , F. Ferrari
  • , L. Mangone
  • , F. Stracci
  • , F. Bianconi
  • , P. Contiero
  • , G. Tagliabue
  • , L. Molong
  • , J. Rachtan
  • , J. Janowski
  • , A. Kubiak
  • , S. Góźdź
  • , P. Macek
  • , M. Bielska-Lasota
  • , J. Błaszczyk
  • , K. Kępska
  • , J. Bastos
  • , B. Carrito
  • , M. J. Bento
  • , C. Castro
  • , A. Mayer-da-Silva
  • , A. Miranda
  • , V. Zadnig
  • , G. Plavc
  • , L. Gil Majuelo
  • , N. Larrañaga
  • , C. Sabater
  • , A. Torella
  • , R. Marcos-Gragera
  • , M. Puigdemont
  • , E. Molina-Portillo
  • , M. J. Sánchez-Pérez
  • , E. Ardanaz
  • , M. Guevara
  • , J. Galceran
  • , F. Saladié
  • , C. Bouchardy
  •  & E. Fournier

Corresponding author

Correspondence to Milena Sant.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards (N. INT 197/14).

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A list of the members of the European High Resolution Working Group on Breast Cancer is given in the Acknowledgment.

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Sant, M., Meneghini, E., Bastos, J. et al. Endocrine treatment and incidence of relapse in women with oestrogen receptor-positive breast cancer in Europe: a population-based study. Breast Cancer Res Treat 183, 439–450 (2020). https://doi.org/10.1007/s10549-020-05761-9

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