Correspondence

Trastuzumab Treatment in Breast Cancer

N Engl J Med 2006; 354:2186May 18, 2006

Article

To the Editor:

Joensuu and colleagues (Feb. 23 issue)1 report the provocative finding that a short treatment with trastuzumab (for nine weeks) combined with chemotherapy is effective in the adjuvant treatment of HER2-positive breast cancer. At a median follow-up of three years, the effect on event-free survival was in the range of that reported with the administration of trastuzumab for a year after adjuvant chemotherapy.2,3 However, this study lacks a randomized comparison with established regimens; neither the regimen of vinorelbine followed by three cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) nor the docetaxel–FEC sequence can be considered “conventional” adjuvant treatment. Furthermore, a cumulative dose of epirubicin of 180 mg per square meter of body-surface area is likely to be suboptimal in high-risk patients with breast cancer.

Filippo Montemurro, M.D.
Giorgio Valabrega, M.D.
Massimo Aglietta, M.D.
Institute for Cancer Research and Treatment, 10060 Candiolo, Italy
filippo.montemurro@ircc.it

3 References

1. 1

   Joensuu H, Kellokumpu-Lehtinen P-L, Bono P, et al. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med 2006;354:809-820
   Full Text | Web of Science | Medline

2. 2

   Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 2005;353:1659-1672
   Full Text | Web of Science | Medline

3. 3

   Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 2005;353:1673-1684
   Full Text | Web of Science | Medline

Author/Editor Response

Anthracycline- and taxane-containing regimens can be considered standard in the adjuvant treatment of breast cancer with a high risk of recurrence. We used an anthracycline–taxane regimen but reversed the usual sequence of administration with the aim of reducing the frequency of adverse cardiac effects. Single-agent vinorelbine has not been evaluated as an adjuvant treatment for breast cancer.

We administered only three cycles of FEC (epirubicin dose, 60 mg per square meter per cycle) after trastuzumab to limit the risk of heart failure. Despite this limitation, the recurrence-free survival rate was favorable, especially among women who received docetaxel, trastuzumab, and FEC. Regimens containing large doses of epirubicin have good efficacy,1 but a dose of 90 mg per square meter per cycle plus cyclophosphamide and trastuzumab may cause adverse cardiac effects.2 Weekly trastuzumab administered concomitantly with paclitaxel and FEC (epirubicin dose, 75 mg per square meter per cycle) was reported to be associated with limited cardiotoxicity.3

Anthracyclines, taxanes, and trastuzumab are probably good choices for adjuvant treatment of HER2-positive breast cancer, although the optimal way of administering them is not known. It is uncertain whether an anthracycline always needs to be included in the regimen.4

Heikki Joensuu, M.D.
Petri Bono, M.D.
Helsinki University Central Hospital, FIN-00029 Helsinki, Finland

Pirkko Kellokumpu-Lehtinen, M.D.
Tampere University Hospital, FIN-33521 Tampere, Finland

4 References

1. 1

   Bonneterre J, Roche H, Kerbrat P, et al. Epirubicin increases long-term survival in adjuvant chemotherapy of patients with poor-prognosis, node-positive, early breast cancer: 10-year follow-up results of the French Adjuvant Study Group 05 randomized trial. J Clin Oncol 2005;23:2686-2693
   CrossRef | Web of Science | Medline

2. 2

   Untch M, Eidtmann H, du Bois A, et al. Cardiac safety of trastuzumab in combination with epirubicin and cyclophosphamide in women with metastatic breast cancer: results of a phase I trial. Eur J Cancer 2004;40:988-997
   CrossRef | Web of Science | Medline

3. 3

   Buzdar AU, Ibrahim NK, Francis D, et al. 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 2005;23:3676-3685
   CrossRef | Web of Science | Medline

4. 4

   Slamon D, Eiermann W, Pienkowski RN, et al. Phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab with docetaxel, carboplatin and trastuzumab in HER2-positive breast cancer patients: BCIRG 006 study. Breast Cancer Res Treat 2005;94:Suppl 1:S5-S5
   Web of Science

Citing Articles (1)

Citing Articles

1. 1

   Elyse E. Lower, Eleanor Glass, Robbin Blau, Stacy Harman. (2009) HER-2/neu expression in primary and metastatic breast cancer. Breast Cancer Research and Treatment 113:2, 301-306
   CrossRef