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Molecular classification of breast cancer: implications for selection of adjuvant chemotherapy

Nature Clinical Practice Oncology volume 3, pages 621–632 (2006)Cite this article

Abstract

Adjuvant chemotherapy improves survival of patients with stage I–III breast cancer but it is being increasingly recognized that the benefit is not equal for all patients. Molecular characteristics of the cancer affect sensitivity to chemotherapy. In general, estrogen-receptor-negative disease is more sensitive to chemotherapy than estrogren-receptor-positive disease. Large-scale genomic analyses of breast cancer suggest that further molecular subsets may exist within the categories defined by hormone receptor status. It is hoped that the new molecular classification schemes might improve patient selection for therapy. Before any new molecular classification (or predictive test) is adopted for routine clinical use, however, several criteria need to be met. There must be an agreed and reproducible method by which to assign molecular class to a new case. Cancers that belong to different molecular classes must show differences in disease outcome and treatment efficacy that affect management and treatment selection. Also desirable are results from prospective clinical trials that demonstrate improved patient outcome when the new test is used in decision-making, compared with the current standard of care. This Review describes the current limitations and future promises of gene-expression-based molecular classification of breast cancer and how it might impact on selection of adjuvant therapy for individual patients.

Key Points

  • Gene expression profiling of breast cancer has revealed large-scale molecular differences between ER-positive, ER-negative and HER2-amplified cancers

  • It is more appropriate to think of breast cancer as at least two to three distinct diseases than as a single disease with heterogeneous ER and HER expression

  • Molecular classification of breast cancer provides a new framework for the study of breast cancer, but how many robust molecular subtypes exist and how best to assign a molecular class to new cases is currently unknown; standard methods for molecular class determination are needed

  • Multigene signatures can be used to help guide therapy and predict prognosis and response to preoperative chemotherapy

  • The extent to which multigene signatures improve patient outcome compared with current clinicopathologic variable-based predictions is yet to be determined in prospective clinical trials

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Figure 1: Molecular classification of breast cancer through hierarchical clustering with “intrinsic genes”.
Figure 2: Overview of the clinical development stages of various genomic predictors.

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Author information

Authors and Affiliations

  1. Assistant Professor, the Department of Breast Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA

    Fabrice Andre

  2. Associate Professor of Medicine, in the Department of Breast Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA

    Lajos Pusztai

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  1. Fabrice Andre
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Correspondence to Lajos Pusztai.

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Andre, F., Pusztai, L. Molecular classification of breast cancer: implications for selection of adjuvant chemotherapy. Nat Rev Clin Oncol 3, 621–632 (2006). https://doi.org/10.1038/ncponc0636

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