Skip to main content
SpringerLink
Log in

Fifteen-year trends in metastatic breast cancer survival in Greece

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

Abstract

In the metastatic setting, a detected time trend to improved prognosis could be attributed to the corresponding recent advances in the therapeutic approaches. The aim of the current study was to first assess, in a large cohort of well over a thousand patients, the time trends in survival in MBC for the last 15 years and second to explore its association to prognostic factors affecting outcome including therapeutic regimen. This meta-analysis uses individual patient data collected from all the trials on MBC (6 nonrandomized, 4 randomized) conducted by HeCOG from 1991 through 2006. Four 4-year time periods (1991–1994, 1995–1998, 1999–2002, and 2003–2006) were constructed for exploration of time trends in survival according to the patient’s date of metastatic diagnosis. Different first line regimens in the 10 trials include anthracycline monotherapy (epirubicin, in the early 1990s) and taxane-containing regimens either as monotherapy or in different combinations with anthracyclines or other drugs. In two phase II studies and in the last randomized study, trastuzumab was administered in all the patients with HER2 overexpressing tumors. In this study, information is based on a total of 1361 patients with a median follow up of 3.7 years and median survival of 1.9 years (median survival 1.28, 1.68, 2.20, and 2.57 years for 1991–1994, 1995–1998, 1999–2002, and 2003–2006, respectively). Survival improved significantly across diagnosis time periods, by 25, 44, and 51%, respectively, in each time period (1995–1998: HR = 0.75, P = 0.004; 1999–2002: HR = 0.56, P < 0.001; 2003–2006: HR = 0.49, P < 0.001) as compared to the first time period (1991–1994). The effect of metastatic diagnosis time period remains almost unchanged in the presence of the following significant prognostic factors: performance status, hormonal receptor status, previous adjuvant chemotherapy, previous adjuvant hormonal treatment, visceral metastasis at entry, and number of metastatic sites. When exploring the effect of new systemic treatment introduction, taking into account the same significant prognostic factors, the effect of diagnosis time period disappears, and the survival improvement is explained directly by the introduction of new agents (hormonal treatment for metastatic disease: yes vs. no: HR = 0.72, P < 0.001; taxanes at first line: yes vs. no: HR = 0.69, P = 0.002; trastuzumab at first line: yes vs. no: HR = 0.63, P < 0.001). The results of this study provide significant evidence of improvement in prognosis of MBC patients within the last 15 years, taking into account all the important significant prognostic factors, and this improvement can be attributed to the use of new systemic treatment agents in the management of the disease.

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
Fig. 5

Similar content being viewed by others

References

  1. Largillier R, Ferrero JM, Doyen J, Barriere J, Namer M, Mari V, Courdi A, Hannoun-Levi JM, Ettore F, Birtwisle-Peyrottes I, Balu-Maestro C, Marcy PY, Raoust I, Lallement M, Chamorey E (2008) Prognostic factors in 1,038 women with metastatic breast cancer. Ann Oncol 19(12):2012–2019

    Article  CAS  PubMed  Google Scholar 

  2. Ferlay J, Autier P, Boniol M, Heanue M, Colombet M, Boyle P (2007) Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol 18(3):581–592

    Article  CAS  PubMed  Google Scholar 

  3. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ (2009) Cancer statistics, 2009. CA Cancer J Clin 59:225–249

    Article  PubMed  Google Scholar 

  4. Dawood S, Broglio K, Gonzalez-Angulo AM, Buzdar AU, Hortobagyi GN, Giordano SH (2008) Trends in survival over the past two decades among white and black patients with newly diagnosed stage IV breast cancer. J Clin Oncol 26(30):4891–4898

    Article  PubMed  Google Scholar 

  5. Giordano SH, Buzdar AU, Smith TL, Kau SW, Yang Y, Hortobagyi GN (2004) Is breast cancer survival improving? Cancer 100(1):44–52

    Article  PubMed  Google Scholar 

  6. Gennari A, Conte P, Rosso R, Orlandini C, Bruzzi P (2005) Survival of metastatic breast carcinoma patients over a 20-year period: a retrospective analysis based on individual patient data from six consecutive studies. Cancer 104(8):1742–1750

    Article  PubMed  Google Scholar 

  7. Andre F, Slimane K, Bachelot T, Dunant A, Namer M, Barrelier A, Kabbaj O, Spano JP, Marsiglia H, Rouzier R, Delaloge S, Spielman M (2004) Breast cancer with synchronous metastases: Trends in survival during a 14-year period. J Clin Oncol 22:3302–3308

    Article  PubMed  Google Scholar 

  8. Fountzilas G, Skarlos D, Katsohis C, Pavlidis N, Giannakakis T, Bafaloukos D, Fahantidis E, Klouvas G, Beer M, Kosmidis P (1995) High-dose epirubicin and r-met-hu G-CSF (filgrastim) in the treatment of patients with advanced breast cancer: a Hellenic Cooperative Oncology Group study. Med Pediatr Oncol 24(1):23–28

    Article  CAS  PubMed  Google Scholar 

  9. Fountzilas G, Scarlos D, Giannakakis T, Athanasiades A, Bafaloukos D, Kalogera-Fountzila A, Bamia C, Pavlidis N, Kosmidis P (1994) Intensive chemotherapy with high-dose Epirubicin every 2 weeks and prophylactic administration of Filgrastim in advanced breast cancer. Eur J Cancer 30A(7):965–969

    Article  CAS  PubMed  Google Scholar 

  10. Fountzilas G, Athanasiades A, Giannakakis T, Brasoulis E, Bafaloukos D, Kalogera-Fountzila A, Onienaoum A, Kalofonos H, Pectasides D, Andreopoulou E, Bamia C, Kosmidis P, Pavlidis N, Skarlos D (1997) A randomised study of Epirubicin monotherapy every four or every two weeks in advanced breast cancer. A Hellenic Cooperative Oncology Group study. Ann Oncol 8(12):1213–1220

    Article  CAS  PubMed  Google Scholar 

  11. Fountzilas G, Dimopoulos ΑΜ, Papadimitriou C, Kalogera-Fountzila A, Aravantinos G, Bafaloukos D, Athanassiades A, Nicolaides C, Keramopoulos A, Pavlidis N, Kosmidis P, Skarlos D (1998) First-line chemotherapy with paclitaxel by three-hour infusion and carboplatin in advanced breast cancer (final report): a phase II study conducted by the Hellenic Oncology Group. Ann Oncol 9(9):1031–1034

    Article  CAS  PubMed  Google Scholar 

  12. Razis Ε, Dimopoulos ΑΜ, Bafaloukos D, Papadimitriou C, Kalogera-Fountzila A, Kalofonos H, Briassoulis E, Samantas E, Keramopoulos A, Pavlidis N, Kosmidis P, Fountzilas G (2001) Dose-dense sequential chemotherapy with epirubicin and paclitaxel in advanced breast cancer. Cancer Invest 19(2):137–144

    Article  CAS  PubMed  Google Scholar 

  13. Fountzilas G, Papadimitriou C, Dafni U, Bafaloukos D, Skarlos D, Moulopoulos LA, Razis E, Kalofonos HP, Aravantinos G, Briassoulis E, Papakostas P, Abela K, Gogas E, Kosmidis P, Pavlidis N, Dimopoulos ΑΜ (2001) Dose-dense sequential chemotherapy with epirubicin and paclitaxel versus the combination, as first-line chemotherapy, in advanced breast cancer: a randomized study conducted by the Hellenic Cooperative Oncology Group. J Clin Oncol 19(8):2232–2239

    CAS  PubMed  Google Scholar 

  14. Fountzilas G, Tsavdaridis D, Kalogera-Fountzila A, Christodoulou CH, Timotheadou E, Kalofonos HP, Kosmidis P, Adamou A, Papakostas P, Gogas H, Stathopoulos G, Razis E, Bafaloukos D, Skarlos D (2001) Weekly paclitaxel as first-line chemotherapy and trastuzumab in patients with advanced breast cancer: a Hellenic Cooperative Oncology Group phase II study. Ann Oncol 12(11):1545–1551

    Article  CAS  PubMed  Google Scholar 

  15. Fountzilas G, Kalofonos HP, Dafni U, Papadimitriou C, Bafaloukos D, Papakostas P, Kalogera-Fountzila A, Gogas H, Aravantinos G, Moulopoulos LA, Economopoulos T, Pectasides D, Maniadakis N, Siafaka V, Briasoulis E, Christodoulou C, Tsavdaridis D, Makrantonakis P, Razis E, Kosmidis P, Skarlos D, Dimopoulos MA (2004) Paclitaxel and epirubicin versus paclitaxel and carboplatin, as first line chemotherapy in patients with advanced breast cancer: a phase III study conducted by the Hellenic Cooperative Oncology Group. Ann Oncol 15(10):1517–1526

    Article  CAS  PubMed  Google Scholar 

  16. Fountzilas G, Christodoulou C, Tsavdaridis D, Kalogera-Fountzila A, Aravantinos G, Razis E, Kalofonos HP, Papakostas P, Karina M, Gogas H, Skarlos D (2004) Paclitaxel and gemcitabine as a first-line chemotherapy combined with trastuzumab in patients with advanced breast cancer. A phase II study conducted by the Hellenic Cooperative Oncology Group (HeCOG). Cancer Invest 22(5):655–662

    Article  CAS  PubMed  Google Scholar 

  17. Fountzilas G, Dafni U, Dimopoulos MA, Koutras A, Skarlos D, Papakostas P, Gogas H, Bafaloukos D, Kalogera-Fountzila A, Samantas E, Briasoulis E, Pectasides D, Maniadakis N, Matsiakou F, Aravantinos G, Papadimitriou C, Karina M, Christodoulou C, Kosmidis P, Kalofonos HP (2009) A randomized phase III study comparing three anthracycline-free taxane-based regimens, as first line chemotherapy, in metastatic breast cancer. A Hellenic Cooperative Oncology Group study. Breast Cancer Res Treat 115(1):87–99

    Article  CAS  PubMed  Google Scholar 

  18. Smith CT, Williamson PR, Marson AG (2005) An overview of methods and empirical comparison of aggregate data and individual patient data results for investigating heterogeneity in meta-analysis of time-to-event outcomes. J Eval Clin Pract 11(5):468–478

    Article  PubMed  Google Scholar 

  19. Smith CT, Williamson PR, Marson AG (2005) Investigating heterogeneity in an individual patient data meta-analysis of time to event outcomes. Stat Med 15 24(9):1307–1319

    Article  Google Scholar 

  20. Information about RevMan available at the relevant web site of Cochrane Collaboration: http://www.cc-ims.net/RevMan

  21. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analysis. BMJ 327(7414):557–560. Review

    Google Scholar 

  22. Shuster JJ (1991) Median follow up in clinical trials. J Clin Oncol 9(1):191–192

    CAS  PubMed  Google Scholar 

  23. Chia SK, Speers CH, D’yachkova Y, Kang A, Malfair-Taylor S, Barnett J, Coldman A, Gelmon KA, O’Reilly SE, Olivotto IA (2007) The impact of new chemotherapeutic and hormone agents on survival in a population-based cohort of women with metastatic breast cancer. Cancer 110(5):973–979

    Article  PubMed  Google Scholar 

  24. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L (2001) Use of chemotherapy plus a monoclonal antibody against Her2 for metastatic breast cancer that overexpresses Her2. N Engl J Med 344:783–792

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Biostatistics, Department of Nursing, School of Health Sciences, University of Athens, Papadiamantopoulou 123, Athens, 11527, Greece

    U. Dafni & A. Xyrafas

  2. Hellenic Cooperative Oncology Group (HeCOG), Athens, Greece

    I. Grimani, A. G. Eleftheraki & G. Fountzilas

  3. Department of Medical Oncology, Papageorgiou Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece

    G. Fountzilas

Authors
  1. U. Dafni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. Grimani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Xyrafas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. G. Eleftheraki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. Fountzilas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to U. Dafni.

Additional information

This study was supported by the Hellenic Cooperative Oncology Group, Athens, Greece.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dafni, U., Grimani, I., Xyrafas, A. et al. Fifteen-year trends in metastatic breast cancer survival in Greece. Breast Cancer Res Treat 119, 621–631 (2010). https://doi.org/10.1007/s10549-009-0630-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-009-0630-8

Keywords

Search

Navigation