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Taxanes: optimizing adjuvant chemotherapy for early-stage breast cancer

Nature Reviews Clinical Oncology volume 7, pages 22–36 (2010)Cite this article

Abstract

Taxanes are among the most widely used chemotherapy agents for advanced breast cancer. Results are now available from 21 trials that randomly allocated nearly 36,000 women with early-stage breast cancer to receive first-generation taxane-based adjuvant chemotherapy versus non-taxane-based adjuvant regimens. Three recent meta-analyses suggest that taxanes are beneficial in the adjuvant setting, irrespective of the patient's age, lymph-node involvement, hormone-receptor expression, and HER2 status. Nevertheless, the optimal role for taxanes in the adjuvant management of early-stage breast cancer remains controversial. We review the results of the first-generation taxane trials and discuss possible explanations for the differences observed in these studies, including variation in the 'strength' of anthracycline therapy in the control arms; suboptimal timing, dosing, or schedule of the taxane regimen; a masking effect of trials that included patients with relatively chemotherapy-insensitive luminal A disease; and decreased representation of the putative taxane-sensitive disease subset. Inclusion criteria for future clinical trials must be revised to account for the molecular heterogeneity of breast cancer and further optimize the role of adjuvant taxane therapy in early-stage disease.

Key Points

  • Recent advances in genomic profiling have highlighted the molecular heterogeneity of breast cancer and the differential responsiveness to chemotherapy according to molecular subtype

  • Cumulative anthracycline administration is associated with rare but serious long-term toxic effects

  • The activity of taxanes in metastatic disease, partial non-cross resistance with anthracyclines, and unique mechanism of action of these agents provide a rationale for evaluating taxanes in the adjuvant setting

  • Existing meta-analyses are limited and no clear conclusions regarding the efficacy of taxanes in various patients subgroups can be drawn

  • Determination of ER or HER2 status alone is unlikely to reveal which patients are likely to benefit from the inclusion of a taxane as adjuvant therapy

  • Incorporation of novel biomarkers into clinical trial designs combined with improved classification of molecular subtypes may help to predict which patients are likely to benefit from taxane treatment

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Figure 1: Schematic representation of possible mechanisms of taxane resistance.

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Authors and Affiliations

  1. Department of Medical Oncology, Jules Bordet Institute, Rue Heger-Bordet 1, Brussels, 1000, Belgium

    Philippe L. Bedard & Martine J. Piccart-Gebhart

  2. Department of Oncology, Sandro Pitigliani Medical Oncology Unit, Hospital of Prato, Piazza dell'Ospedale, Prato, 59100, Italy

    Angelo Di Leo

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Correspondence to Martine J. Piccart-Gebhart.

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Angelo Di Leo declares he receives grant/research support, and is a consultant for and receives honoraria from Sanofi–Aventis. Martine J. Piccart–Gebhart declares she is a consultant for Abraxis BioScience, Bristol–Myers Squibb and Sanofi–Aventis. L. Bedard declares no competing interests.

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Bedard, P., Di Leo, A. & Piccart-Gebhart, M. Taxanes: optimizing adjuvant chemotherapy for early-stage breast cancer. Nat Rev Clin Oncol 7, 22–36 (2010). https://doi.org/10.1038/nrclinonc.2009.186

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