Breast Cancer Research and Treatment

, Volume 117, Issue 3, pp 599–601 | Cite as

Never use anthracyclines with trastuzumab: it is time to reconsider the taboo

Invited commentary


Paclitaxel Doxorubicin Trastuzumab Anthracyclines Epirubicin 



Luca Gianni is Advisor to Roche, Genentech, Wyeth and GSK.


  1. 1.
    Slamon DJ, Leyland-Jones B, Shak S et al (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344(11):783–792PubMedCrossRefGoogle Scholar
  2. 2.
    Seidman A, Hudis C, Pierri MK, Shak S, Paton V, Ashby M, Murphy M, Stewart SJ, Keefe D (2002) Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol 20(5):1215–1221PubMedCrossRefGoogle Scholar
  3. 3.
    Sawyer DB, Zuppinger C, Miller TA et al (2002) Modulation of anthracycline-induced myofibrillar disarray in rat ventricular myocytes by neuregulin-1b and anti-erbB2. Potential mechanism for trastuzumab-induced cardiotoxicity. Circulation 105:1551–1554PubMedCrossRefGoogle Scholar
  4. 4.
    Peng X, Chen B, Lim CC, Sawyer DB (2005) The cardiotoxicology of anthracycline chemotherapeutics: translating molecular mechanism into preventative medicine. Mol Interv 5(3):163–171PubMedCrossRefGoogle Scholar
  5. 5.
    Ewer MS, VooletichMT DurandJB et al (2005) Reversibility of trastuzumab-related cardiotoxicity: newinsights based on clinical course and response to medical treatment. J Clin Oncol 23:7820–7826PubMedCrossRefGoogle Scholar
  6. 6.
    Slamon DJ, Mackey J, Robert N et al. (2007) Role of anthracycline-based therapy in the adjuvant treatment of breast cancer: efficacy analyses determined by molecular subtypes of the disease. 30th San Antonio Breast Cancer Symposium, December 13–16 (abstract 13)Google Scholar
  7. 7.
    Stickeler E, Klar M, Watermann D, et al. (2009) Pegylated liposomal doxorubicin and trastuzumab as 1st and 2nd line therapy in Her2/neu positive Metastatic Breast Cancer: A Multicenter Phase II Trial. Breast Cancer Res Treat (this issue)Google Scholar
  8. 8.
    Rayson D, Richel D, Chia S, Jackisch C, van der Vegt S, Suter T (2008) Anthracycline-trastuzumab regimens for HER2/neu-overexpressing breast cancer: current experience and future strategies. Ann Oncol 19(9):1530–1539PubMedCrossRefGoogle Scholar
  9. 9.
    Muss HB, Thor AD, Berry DA, et al. (1994) c-erbB-2 expression and response to adjuvant therapy in women with node-positive early breast cancer. N Engl J Med. 1994 May 5;330(18):1260–6. Erratum in: N Engl J Med 331(3):211Google Scholar
  10. 10.
    Moliterni A, Ménard S, Valagussa P et al (2003) HER2 overexpression and doxorubicin in adjuvant chemotherapy for respectable breast cancer. J Clin Oncol 21(3):458–462PubMedCrossRefGoogle Scholar
  11. 11.
    Gennari A, Sormani MP, Pronzato P et al (2008) HER2 status and efficacy of adjuvant anthracyclines in early breast cancer: a pooled analysis of randomized trials. J Natl Cancer Inst 100(1):14–20PubMedCrossRefGoogle Scholar
  12. 12.
    McArthur HL, Tan LK, Patil S, et al. (2008) High resolution representational oligonucleotide microarray analysis (ROMA) suggests that TOPO2 and HER2 co-amplification is uncommon in human breast cancer. 31st San Antonio Breast Cancer Symposium, December 10–14 2008 (abstract 2023)Google Scholar
  13. 13.
    Bartlett JMS, Munro A, Dunn JA, et al. (2008) Chromosome 17 polysomy (Ch17) as a predictor of anthracycline response: emerging evidence from the UK NEAT adjuvant breast cancer trial. 31st San Antonio Breast Cancer Symposium, December 10-14 2008 (abstract 45)Google Scholar
  14. 14.
    Bianchi G, Albanell J, Eiermann W et al (2003) Pilot trial of trastuzumab starting with or after the doxorubicin component of a doxorubicin plus paclitaxel regimen for women with HER2-positive advanced breast cancer. Clin Cancer Res 9:5944–5951PubMedGoogle Scholar
  15. 15.
    Gianni L, Eiermann W, Semiglazov V, et al. Neoadjuvant trastuzumab in patients with HER2-positive locally advanced breast cancer: primary efficacy analysis of the NOAH trial. 31st San Antonio Breast Cancer Symposium, December 10–14 2008 (abstract 31)Google Scholar
  16. 16.
    Buzdar AU, Ibrahim NK, Francis D et al (2005) Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol 23:3676–3685PubMedCrossRefGoogle Scholar
  17. 17.
    Untch M, Tjulandin S, Jonat W, et al. (2007) Evaluation of first-line trastuzumab in combination with epirubicin/cyclophosphamide for patients with HER2-positive metastatic breast cancer. 30th San Antonio Breast Cancer Symposium, December 13–16 2007 (abstract 4058)Google Scholar
  18. 18.
    Untch M, Rezai M, Loibl S, et al. (2007) Evaluating the efficacy and safety of trastuzumab given concomitantly to epirubicin/cyclophosphamide® docetaxel ± capecitabine as neoadjuvant treatment of HER2 overexpressing primary breast cancer. First analysis of the GBG/AGO intergroup-study “GeparQuattro”. Breast Cancer Res Treat 106:2007 (suppl 1; abstract 5053)Google Scholar
  19. 19.
    Chia S, Clemons M, Martin LA et al (2006) Pegylated liposomal doxorubicin and trastuzumab in HER-2 overexpressing metastatic breast cancer: amulticenter phase II trial. J Clin Oncol 24:2773–2778PubMedCrossRefGoogle Scholar
  20. 20.
    Wolff A, Bonetti M, Sparano J et al (2003) Cardiac safety of trastuzumab (H) in combination with pegylated liposomal doxorubicin (D) and docetaxel (T) in HER2-positive metastatic breast cancer (MBC): preliminary results of the Eastern Cooperative Oncology Group trial E3198. Proc Am Soc Clin Oncol 22:A70Google Scholar
  21. 21.
    Andreopoulou E, Gaiotti D, Kim E et al (2007) Feasibility and cardiac safety of pegylated liposomal doxorubicin plus trastuzumab in heavily pretreated patients with recurrent HER2-overexpressing metastatic breast cancer. Clin Breast Cancer 7:690–696PubMedCrossRefGoogle Scholar
  22. 22.
    Theodoulou M, Campos SM, Batist G et al (2002) TLC D99 (D, Myocet) and herceptin (H) is safe in advanced breast cancer (ABC): final cardiac safety and efficacy analysis. Proc Am Soc Clin Oncol 21:55aGoogle Scholar
  23. 23.
    Cortes J, DiCosimo S, Climent MA et al (2009) Nonpegylated liposomal doxorubicin (TLC-D99), paclitaxel, and trastuzumab in HER-2-overexpressing breast cancer: a multicenter phase I/II study. Clin Cancer Res 15(1):307–314PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  1. 1.Medical Oncology 1Istituto dei Tumori di MilanoMilanItaly

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