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  • Review Article
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Facts and controversies in the use of trastuzumab in the adjuvant setting

Nature Clinical Practice Oncology volume 5, pages 645–654 (2008)Cite this article

Abstract

The human epidermal growth factor receptor-2 (HER2) is overexpressed and/or amplified in up to 25% of breast cancer patients, and this feature is associated with an aggressive phenotype, high recurrence rate and reduced survival. Until recently, combination chemotherapy (with or without endocrine therapy) was the only effective adjuvant treatment for HER2-positive patients. Trastuzumab is a monoclonal antibody directed against the HER2 extracellular domain, and five recent adjuvant breast cancer trials have demonstrated an astonishing and highly reproducible benefit in halving the recurrence rate and reducing mortality in patients with this phenotype. Many questions related to trastuzumab use in the adjuvant setting still remain; these include the optimum timing and duration of treatment, trastuzumab use with taxanes and radiotherapy, its role in small node-negative tumors, the optimum chemotherapy regimens and cost-effectiveness. This Review outlines the five adjuvant trastuzumab studies and discusses the controversies and challenges that have emerged for both the clinician and healthcare authorities worldwide as a consequence of the results from these trials.

Key Points

  • Five adjuvant trials with trastuzumab have shown clinical benefit in reducing recurrence rate and improving overall survival; however, many controversies remain regarding adjuvant trastuzumab use owing to the varying trial designs and patient populations

  • The optimum timing of trastuzumab initiation is unclear, although delayed therapy does not seem to be less efficacious and combined therapy (with taxanes with and without radiotherapy) is no more toxic

  • The empirical standard for trastuzumab therapy is 12 months, although there is evidence from the FinHer trial for a shorter duration of treatment

  • Results from the NCCTG-N9831 trial show that concurrent administration with taxanes may be more efficacious, but more cardiac events were also noted

  • Endocrine responsiveness may be a useful tool to further stratify HER2-positive, node-negative patients with tumors smaller than 1 cm

  • Optimum chemotherapy regimens have not been defined, but early evidence for non-anthracycline regimens is promising

  • Trastuzumab is cost-effective but still not affordable for many countries

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Figure 1: Annualized disease-free survival hazard rates for 1 year of trastuzumab versus observation.

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Author information

Authors and Affiliations

  1. P Dinh is a Clinical Research Fellow, E de Azambuja is a Medical Oncologist, F Cardoso is Assistant Professor and MJ Piccart-Gebhart is Professor, all at the Medical Oncology Clinic, Institut Jules Bordet, Brussels, Belgium.,

    Phuong Dinh, Evandro de Azambuja, Fatima Cardoso & Martine J Piccart-Gebhart

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  1. Phuong Dinh
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  2. Evandro de Azambuja
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  3. Fatima Cardoso
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  4. Martine J Piccart-Gebhart
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Corresponding author

Correspondence to Martine J Piccart-Gebhart.

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Competing interests

MJ Piccart-Gebhart is a consultant for Boehringer Ingelheim and GlaxoSmithKline, and receives grant/research support from Boehringer Ingelheim, GlaxoSmithKline and Roche. The other authors declared no competing interests.

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Dinh, P., de Azambuja, E., Cardoso, F. et al. Facts and controversies in the use of trastuzumab in the adjuvant setting. Nat Rev Clin Oncol 5, 645–654 (2008). https://doi.org/10.1038/ncponc1219

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