Older patients are poorly represented in breast cancer research and guidelines do not provide evidence based recommendations for this specific group. We compared treatment strategies and survival outcomes between European countries and assessed whether variance in treatment patterns may be associated with variation in survival.


Population-based study including patients aged ≥ 70 with non-metastatic BC from cancer registries from the Netherlands, Belgium, Ireland, England and Greater Poland. Proportions of local and systemic treatments, five-year relative survival and relative excess risks (RER) between countries were calculated.


In total, 236,015 patients were included. The proportion of stage I BC receiving endocrine therapy ranged from 19.6% (Netherlands) to 84.6% (Belgium). The proportion of stage III BC receiving no breast surgery varied between 22.0% (Belgium) and 50.8% (Ireland). For stage I BC, relative survival was lower in England compared with Belgium (RER 2.96, 95%CI 1.30–6.72, P < .001). For stage III BC, England, Ireland and Greater Poland showed significantly worse relative survival compared with Belgium.


There is substantial variation in treatment strategies and survival outcomes in elderly with BC in Europe. For early-stage BC, we observed large variation in endocrine therapy but no variation in relative survival, suggesting potential overtreatment. For advanced BC, we observed higher survival in countries with lower proportions of omission of surgery, suggesting potential undertreatment.

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  1. 1.

    DeSantis CE, Fedewa SA, Goding Sauer A, Kramer JL, Smith RA, Jemal A. Breast cancer statistics, 2015: Convergence of incidence rates between black and white women. CA Cancer J. Clin. 66, 31–42 (2016).

  2. 2.

    Biganzoli, L., Wildiers, H., Oakman, C., Marotti, L., Loibl, S. & Kunkler, I. et al. Management of elderly patients with breast cancer: updated recommendations of the International Society of Geriatric Oncology (SIOG) and European Society of Breast Cancer Specialists (EUSOMA). Lancet Oncol. 13, e148–e60 (2012).

  3. 3.

    Hurria A, Levit LA, Dale W, Mohile SG, Muss HB, Fehrenbacher L et al. Improving the evidence base for treating older adults with cancer: american society of clinical oncology statement. J. Clin. Oncol. 33, 3826–e33 (2015).

  4. 4.

    van de Water W, Kiderlen M, Bastiaannet E, Siesling S, Westendorp R, van de Velde C et al. External validity of a trial comprising elderly patients with hormone-receptor positive breast cancer. J. Natl. Cancer Inst. 106, dju051 (2014).

  5. 5.

    Wildiers, H., Mauer, M., Pallis, A., Hurria, A., Mohile, S. G. & Luciani, A. et al. End points and trial design in geriatric oncology research: a joint European organisation for research and treatment of cancer-alliance for clinical trials in oncology-international society of geriatric oncology position article. J .Clin. Oncol. 31, 3711–3718 (2013).

  6. 6.

    de Glas NA, Hamaker ME, Kiderlen M, de Craen AJ, Mooijaart SP, van de Velde CJ et al. Choosing relevant endpoints for older breast cancer patients in clinical trials: an overview of all current clinical trials on breast cancer treatment. Breast Cancer Res. Treat. 146, 591–597 (2014).

  7. 7.

    de Glas, N. A., Kiderlen, M., de Craen, A. J., Hamaker, M. E., Portielje, J. E. & van de Velde, C. J. et al. Assessing treatment effects in older breast cancer patients: systematic review of observational research methods. Cancer Treat. Rev. 41, 254–261 (2015).

  8. 8.

    Vandenbroucke, J. P. When are observational studies as credible as randomised trials? Lancet 363, 1728–1731 (2004).

  9. 9.

    Organization WH. International Statistical Classification of Diseases and Related Health Problems 10th Revision. 2010.

  10. 10.

    Greene, F. L., Page, D. L. & Fleming, I. D. AJCC cancer staging manual. 6th edn, (Springer, New York, NY, 2002).

  11. 11.

    Fritz, A. P. C., Jack, A., Shanmugaratnam, K., Sobin, L., Parkin, D. M., Whelan, S. eds. International Classification of Diseases for Oncology. 3rd edn, (World Health Organization: Geneva, 2000).

  12. 12.

    Schemper, M. & Smith, T. L. A note on quantifying follow-up in studies of failure time. Control Clin. Trials 17, 343–346 (1996).

  13. 13.

    Perme, M. P., Stare, J. & Esteve, J. On estimation in relative survival. Biometrics 68, 113–120 (2011).

  14. 14.

    Human Mortality Database [Internet]. 2016 [cited 10-09-2016]. Available from: www.mortality.org.

  15. 15.

    Perme, M. P., Henderson, R. & Stare, J. An approach to estimation in relative survival regression. Biostatistics 10, 136–146 (2008).

  16. 16.

    Suissa, S. Relative excess risk: an alternative measure of comparative risk. Am. J. Epidemiol. 150, 279–282 (1999).

  17. 17.

    Nur, U., Shack, L. G., Rachet, B., Carpenter, J. R. & Coleman, M. P. Modelling relative survival in the presence of incomplete data: a tutorial. Int J. Epidemiol. 39, 118–128 (2010).

  18. 18.

    Giorgi, R., Belot, A., Gaudart, J. & Launoy, G. The performance of multiple imputation for missing covariate data within the context of regression relative survival analysis. Stat. Med. 27, 6310–6331 (2008).

  19. 19.

    Sant M, Chirlaque Lopez MD, Agresti R, Sanchez Perez MJ, Holleczek B, Bielska-Lasota M et al. Survival of women with cancers of breast and genital organs in Europe 1999-2007: results of the EUROCARE-5 study. Eur. J. Cancer. 51, 2191–2205 (2015).

  20. 20.

    de Glas NA, Jonker JM, Bastiaannet E, de Craen AJ, van de Velde CJ, Siesling S et al. Impact of omission of surgery on survival of older patients with breast cancer. Br. J. Surg. 101, 1397–1404 (2014).

  21. 21.

    Holleczek, B. & Brenner, H. Trends of population-based breast cancer survival in Germany and the US: decreasing discrepancies, but persistent survival gap of elderly patients in Germany. BMC Cancer 12, 317 (2012).

  22. 22.

    NABON. Richtlijn Mammacarcinoom versie 2. 02012. updated 13 February 2012. Available from: www.oncoline.nl/mammacarcinoom.

  23. 23.

    Kiderlen, M., Walsh, P. M., Bastiaannet, E., Kelly, M. B., Audisio, R. A. & Boelens, P. G. et al. Treatment strategies and survival of older breast cancer patients - an international comparison between the Netherlands and Ireland. PLoS ONE 10, e0118074 (2015).

  24. 24.

    Christiansen, P., Bjerre, K., Ejlertsen, B., Jensen, M. B., Rasmussen, B. B. & Laenkholm, A. V. et al. Mortality rates among early-stage hormone receptor-positive breast cancer patients: a population-based cohort study in Denmark. J. Natl. Cancer Inst. 103, 1363–1372 (2011).

  25. 25.

    Hind, D., Wyld, L. & Reed, M. W. Surgery, with or without tamoxifen, vs tamoxifen alone for older women with operable breast cancer: cochrane review. Br. J. Cancer 96, 1025–1029 (2007).

  26. 26.

    Kunkler, I. H., Williams, L. J., Jack, W. J., Cameron, D. A. & Dixon, J. M. Breast-conserving surgery with or without irradiation in women aged 65 years or older with early breast cancer (PRIME II): a randomised controlled trial. Lancet Oncol. 16, 266–273 (2015).

  27. 27.

    Allemani, C., Storm, H., Voogd, A. C., Holli, K., Izarzugaza, I. & Torrella-Ramos, A. et al. Variation in ‘standard care’ for breast cancer across Europe: a EUROCARE-3 high resolution study. Eur. J. Cancer 46, 1528–1536 (2010).

  28. 28.

    Senkus, E., Kyriakides, S., Ohno, S., Penault-Llorca, F., Poortmans, P. & Rutgers, E. et al. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 26, v8–30 (2015).

  29. 29.

    Peto, R., Davies, C., Godwin, J., Gray, R., Pan, H. C. & Clarke, M. 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 379, 432–444 (2011).

  30. 30.

    Crivellari, D., Gray, K. P., Dellapasqua, S., Puglisi, F., Ribi, K. & Price, K. N. et al. Adjuvant pegylated liposomal doxorubicin for older women with endocrine nonresponsive breast cancer who are NOT suitable for a “standard chemotherapy regimen”: the CASA randomized trial. Breast 22, 130–137 (2013).

  31. 31.

    Leonard, R., Ballinger, R., Cameron, D., Ellis, P., Fallowfield, L. & Gosney, M. et al. Adjuvant chemotherapy in older women (ACTION) study - what did we learn from the pilot phase? Br. J. Cancer 105, 1260–1266 (2011).

  32. 32.

    Wysocki KHAAŚAWM. Breast cancer treatment outcomes, therapy options and costs in Poland (2005–2007). J Oncol 64, 33–39 2014.

  33. 33.

    Munro, A. J. Interpretation of EUROCARE-5. Lancet Oncol. 15, 2–3 (2014).

  34. 34.

    Meropol, N. J., Egleston, B. L., Buzaglo, J. S., Benson, A. B. III, Cegala, D. J. & Diefenbach, M. A. et al. Cancer patient preferences for quality and length of life. Cancer 113, 3459–3466 (2008).

  35. 35.

    Hamelinck VC, Bastiaannet E, Pieterse AH, Merkus JWS, Jannink I, den Hoed IDM et al. A prospective comparison of younger and older patients’ preferences for breast-conserving surgery versus mastectomy in early breast cancer. J. Geriatr. Oncol. 9, 170–173 (2017).

  36. 36.

    Fried, T. R., Bradley, E. H., Towle, V. R. & Allore, H. Understanding the treatment preferences of seriously ill patients. N. Engl. J. Med. 346, 1061–1066 (2002).

  37. 37.

    Hamelinck, V. C., Bastiaannet, E., Pieterse, A. H., de Glas, N. A., Portielje, J. E. & Merkus, J. W. et al. A prospective comparison of younger and older patients’ preferences for adjuvant chemotherapy and hormonal therapy in early breast cancer. Clin. Breast Cancer 16, 379–388 (2016).

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We thank all the members of the EURECCA Breast Cancer group for data collection and preparation of the data sets. Furthermore, we thank Michel P. Villerius for sharing his knowledge on high performance computing and for his help with the implementation of our planned analysis.

Authors Contributon

MD and EB contributed to study design, data preparation, data analysis and interpretation, prepared the first draft of the report, contributed to subsequent versions and the final report. JP, GL, PB and LW contributed to data interpretation, reviewed the first draft of the report, subsequent versions and the final version. MK initiated the study, contributed to data preparation and interpretation, reviewed to the first draft of the report, subsequent versions and the final version. DH contributed to data preparation and interpretation, reviewed to the first draft of the report, subsequent versions and the final version. PW, EE, SS, JB, MT, AK, JCF, TN, WZ and AG contributed to data collection, data interpretation, reviewed the first draft of the report, subsequent drafts and the final report. RA and CvdV initiated the study, contributed to study design, data interpretation, reviewed the first draft of the report, subsequent drafts and the final report. Contributions are guaranteed by the corresponding author (CvdV).

Author information


  1. Department of Surgery, Leiden University Medical Center, Albinusdreef 2, Leiden, 2333 ZA, The Netherlands

    • Marloes G. M. Derks
    • , Esther Bastiaannet
    • , Mandy Kiderlen
    • , Denise E. Hilling
    • , Petra G. Boelens
    • , Gerrit-Jan Liefers
    •  & Cornelis J. H. van de Velde
  2. Department of Gerontology & Geriatrics, Leiden University Medical Center, Albinusdreef 2, Leiden, 2333 ZA, The Netherlands

    • Esther Bastiaannet
  3. National Cancer Registry of Ireland, Building 6800, Cork Airport Business Park, Kinsale Road, Cork, T12 CDF7, Ireland

    • Paul M. Walsh
  4. Belgian Cancer Registry, Koningsstraat 215, Brussels, 1210, Belgium

    • Elizabeth van Eycken
  5. Department of Research, Netherlands Comprehensive Cancer Organisation (IKNL), Godebaldkwartier 419, Utrecht, 3511 DT, The Netherlands

    • Sabine Siesling
  6. Public Health England, 5 St Philip’s Place, Birmingham, B3 2PW, UK

    • John Broggio
  7. Department of Oncology and Metabolism, University of Sheffield, Western Bank, Sheffield, S10 2TN, UK

    • Lynda Wyld
  8. Greater Poland Cancer Registry, Greater Poland Cancer Center, Garbary 15, Poznań, 60-101, Poland

    • Maciej Trojanowski
  9. Department of Head and Neck Cancer Surgery, Department of Surgical Oncology, Medical University of Lodz, Kościuszki 4, Łódź, 90-419, Poland

    • Agnieszka Kolacinska
  10. Department of Radiotherapy, Medical University of Lodz, Kościuszki 4, Łódź, 90-419, Poland

    • Justyna Chalubinska-Fendler
  11. Portuguese Oncology Institute of Porto, R. Dr. António Bernardino de Almeida 62, Porto, 4200-162, Portugal

    • Ana Filipa Gonçalves
  12. Department of Surgical Oncology, Ludwik Rydygier’s Collegium Medicum, Jagiellońska 13-15, Bydgoszcz, 85-067, Poland

    • Tomasz Nowikiewicz
    •  & Wojciech Zegarski
  13. Department of Surgery, St Helens Teaching Hospital, University of Liverpool, Marshalls Cross Rd, Saint Helens, St Helens, WA9 3DA, UK

    • Riccardo A. Audisio
  14. Department of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, Leiden, 2333 ZA, The Netherlands

    • Johanneke E. A. Portielje


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  1. on behalf of the EURECCA Breast Cancer Group

    Conflict of interest

    The authors declare that they have no conflict of interest.

    Ethical approval

    Cancer registries provided anonymised patient data. Therefore, informed consent from patients or ethical approval were not required for this study.

    Availability of data

    Patient level data are available upon request from the separate participating cancer registries. Access to the full data set will be provided if each participating cancer registry gives permission for data sharing. Statistical code is available upon request with the corresponding author.


    This work was supported by the European Society of Surgical Oncology (ESSO). The funding source had no role in the study design, data collection, analysis, interpretation of the data, writing of the manuscript, or the decision to publish. Researchers were independent from the funding source.


    This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).

    Corresponding author

    Correspondence to Cornelis J. H. van de Velde.

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