Skip to main content

Trastuzumab re-treatment following adjuvant trastuzumab and the importance of distant disease-free interval: the HERA trial experience

Breast Cancer Research and Treatment volume 155, pages 127–132 (2016)Cite this article

Abstract

This retrospective analysis conducted using data from patients enrolled onto the Herceptin Adjuvant has two objectives: The first is to evaluate the impact of the time interval between the end of adjuvant trastuzumab and distant recurrence (TDRI) upon overall survival (OS). The second is to describe the duration of trastuzumab-based regimens in the metastatic setting for patients previously treated with adjuvant trastuzumab. The first objective included 187 patients treated with adjuvant trastuzumab and diagnosed with distant recurrence at 4-year median follow-up. The second objective included data from questionnaires sent to investigators retreating patients with trastuzumab upon distant recurrence: 144 of 156 questionnaires were returned (93 %), and 90 patients were selected based on available clinical information and consent for subsequent studies. There was no statistically significant relationship between TDRI following 1 year of adjuvant trastuzumab and OS from distant recurrence: hazard ratio 0.991, p = 0.46. The median OS from distant recurrence was numerically longer among patients with a TDRI of ≥12 months (n = 103) than <12 months (n = 84) but not statistically significant (23.7 vs. 17.8 months, p = 0.47). The median duration of first-line trastuzumab-based regimens for patients previously treated with adjuvant trastuzumab and diagnosed with distant disease recurrence was 8.8 months (n = 88). This retrospective, exploratory study suggests that TDRI did not impact on OS measured from distant recurrence. We argue that prospective collection of treatment information beyond disease progression should be included in future clinical studies.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3

References

  1. Verma S et al (2012) Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 367(19):1783–1791

    Article  PubMed  CAS  Google Scholar 

  2. Baselga J et al (2012) Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 366(2):109–119

    Article  PubMed  CAS  Google Scholar 

  3. Piccart-Gebhart MJ et al (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353(16):1659–1672

    Article  PubMed  CAS  Google Scholar 

  4. Romond EH et al (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353(16):1673–1684

    Article  PubMed  CAS  Google Scholar 

  5. Slamon D et al (2011) Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 365(14):1273–1283

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  6. Smith I et al (2007) 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 369(9555):29–36

    Article  PubMed  CAS  Google Scholar 

  7. Gianni L et al (2011) Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial. Lancet Oncol 12(3):236–244

    Article  PubMed  CAS  Google Scholar 

  8. Tripathy D et al (2004) Safety of treatment of metastatic breast cancer with trastuzumab beyond disease progression. J Clin Oncol 22(6):1063–1070

    Article  PubMed  CAS  Google Scholar 

  9. Petrelli F, Barni S (2013) A pooled analysis of 2618 patients treated with trastuzumab beyond progression for advanced breast cancer. Clin Breast Cancer 13(2):81–87

    Article  PubMed  CAS  Google Scholar 

  10. Campiglio M et al (2011) Increased overall survival independent of RECIST response in metastatic breast cancer patients continuing trastuzumab treatment: evidence from a retrospective study. Breast Cancer Res Treat 128(1):147–154

    Article  PubMed  CAS  Google Scholar 

  11. Extra JM et al (2010) Efficacy of trastuzumab in routine clinical practice and after progression for metastatic breast cancer patients: the observational Hermine study. Oncologist 15(8):799–809

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  12. von Minckwitz G et al (2009) Trastuzumab beyond progression in human epidermal growth factor receptor 2-positive advanced breast cancer: a german breast group 26/breast international group 03–05 study. J Clin Oncol 27(12):1999–2006

    Article  Google Scholar 

  13. Krop IE et al (2014) Trastuzumab emtansine versus treatment of physician’s choice for pretreated HER2-positive advanced breast cancer (TH3RESA): a randomised, open-label, phase 3 trial. Lancet Oncol 15(7):689–699

    Article  PubMed  CAS  Google Scholar 

  14. Valagussa P, Tancini G, Bonadonna G (1986) Salvage treatment of patients suffering relapse after adjuvant CMF chemotherapy. Cancer 58(7):1411–1417

    Article  PubMed  CAS  Google Scholar 

  15. Buzdar AU et al (1981) Management of breast cancer patients failing adjuvant chemotherapy with adriamycin-containing regimens. Cancer 47(12):2798–2802

    Article  PubMed  CAS  Google Scholar 

  16. Lang I et al (2014) Trastuzumab retreatment after relapse on adjuvant trastuzumab therapy for human epidermal growth factor receptor 2-positive breast cancer: final results of the retreatment after Herceptin Adjuvant trial. Clin Oncol (R Coll Radiol) 26(2):81–89

    Article  CAS  Google Scholar 

  17. Baselga J et al (2011) Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 366(2):109–119

    Article  PubMed  Google Scholar 

  18. Swain SM et al (2013) Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol 14(6):461–471

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  19. Murthy RK et al (2014) Effect of adjuvant/neoadjuvant trastuzumab on clinical outcomes in patients with HER2-positive metastatic breast cancer. Cancer 120(13):1932–1938

    Article  PubMed  CAS  Google Scholar 

  20. Vaz-Luis I et al (2013) Clinicopathological features among patients with advanced human epidermal growth factor-2-positive breast cancer with prolonged clinical benefit to first-line trastuzumab-based therapy: a retrospective cohort study. Clin Breast Cancer 13(4):254–263

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  21. Negri E et al (2014) Effectiveness of trastuzumab in first-line HER2+ metastatic breast cancer after failure in adjuvant setting: a controlled cohort study. Oncologist 19(12):1209–1215

    Article  PubMed  CAS  PubMed Central  Google Scholar 

Download references

Acknowledgments

We thank the women who participated in this study; the Breast European Adjuvant Study Team Data Centre; the Frontier Science Team; the Breast International Group Secretariat; the HERA steering committee; the Independent Data Monitoring Committee; F Hoff mann-La Roche; and the doctors who participated in HERA.

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue Yawkey, Boston, 1238, USA

    Otto Metzger-Filho

  2. Department of Medical Oncology and Breast European Adjuvant Study Team (BrEAST) Data Centre, Institut Jules Bordet and Université Libre de Bruxelles, Brussels, Belgium

    Evandro de Azambuja

  3. Frontier Science (Scotland) Ltd, Kincraig, Kingussie, UK

    Marion Procter

  4. Breast European Adjuvant Study Team (BrEAST) Data Centre, Institut Jules Bordet and Université Libre de Bruxelles, Brussels, Belgium

    Magalie Krieguer

  5. Breast Unit, Royal Marsden Hospital, and Institute of Cancer Research, London, UK

    Ian Smith

  6. Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Jose Baselga

  7. Edinburgh Cancer Research Centre, Western general Hospital, University of Edinburgh, Crewe Road South, Edinburgh, UK

    David Cameron

  8. Department of Gynecology and Obstetrics and Multidisciplinary Breast Cancer Center, Helios Klinikum, Berlin-Buch, Germany

    Michael Untch

  9. Department of Gynecology and Obstetrics, Klinikum Off enbach, Off Enbach, Germany

    Christian Jackisch

  10. Department of Medical Oncology, The Andrew Love Cancer Centre, Deakin University, Geelong, Australia

    Richard Bell

  11. Department of Medical Oncology, San Raffaele Institute, Milan, Italy

    Luca Gianni

  12. European Institute of Oncology, Milan, Italy

    Aron Goldhirsch

  13. Swiss Center for Breast Health, Sant’Anna Clinic, Lugano-Sorengo, Switzerland

    Aron Goldhirsch

  14. Department of Medicine, Institut Jules Bordet and Université Libre de Bruxelles, Brussels, Belgium

    Martine Piccart

  15. Department of Biostatistics and Computational Biology, International Breast Cancer Study Group (IBCSG) Statistical Center, Dana-Farber Cancer Institute, Harvard School of Public Health, Harvard Medical School, Boston, USA

    Richard D. Gelber

Authors
  1. Otto Metzger-Filho
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Evandro de Azambuja
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marion Procter
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Magalie Krieguer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ian Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jose Baselga
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. David Cameron
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Michael Untch
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Christian Jackisch
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Richard Bell
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Luca Gianni
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Aron Goldhirsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Martine Piccart
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Richard D. Gelber
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

HREA Study Team

Corresponding author

Correspondence to Otto Metzger-Filho.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Metzger-Filho, O., de Azambuja, E., Procter, M. et al. Trastuzumab re-treatment following adjuvant trastuzumab and the importance of distant disease-free interval: the HERA trial experience. Breast Cancer Res Treat 155, 127–132 (2016). https://doi.org/10.1007/s10549-015-3656-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-015-3656-0

Keywords

  • Breast cancer
  • Disease-free survival
  • HER2+