EJC Supplements
Volume 9, Issue 2 , Pages 16-21, October 2011

Predictive molecular markers of anthracycline effectiveness in early breast cancer

  • Angelo Di Leo

      Affiliations

    • “Sandro Pitigliani” Medical Oncology Unit, Department of Oncology, Hospital of Prato, Istituto Toscano Tumori, Prato, Italy
    • Corresponding Author InformationCorresponding author. Angelo Di Leo, “Sandro Pitigliani” Medical Oncology Unit, Department of Oncology, Hospital of Prato, Piazza dell'Ospedale 2, 59100 Prato, Italy. Tel.: +39 0574 434766; fax: +39 0574 29798
    • ,
  • Erica Moretti

      Affiliations

    • “Sandro Pitigliani” Medical Oncology Unit, Department of Oncology, Hospital of Prato, Istituto Toscano Tumori, Prato, Italy
    • ,
  • Catherine Oakman

      Affiliations

    • “Sandro Pitigliani” Medical Oncology Unit, Department of Oncology, Hospital of Prato, Istituto Toscano Tumori, Prato, Italy
    • ,
  • Laura Biganzoli

      Affiliations

    • “Sandro Pitigliani” Medical Oncology Unit, Department of Oncology, Hospital of Prato, Istituto Toscano Tumori, Prato, Italy
    • ,
  • Libero Santarpia

      Affiliations

    • Translational Research Unit, Department of Oncology, Hospital of Prato, Istituto Toscano Tumori, Prato, Italy

Article Outline

Abstract 

The past decade has seen extensive research into potential markers of responsiveness to anthracycline therapy in breast cancer patients; however, such markers have remained elusive. The status of both human epidermal growth factor receptor-2 (HER2) and topoisomerase II alpha (TOP2A) genes has been investigated in this context, but neither can be considered a clinically reliable predictor of response to anthracyclines. Expression of the TOP2A protein is affected by a number of factors not always related to gene copy number, and these might provide future potential markers. Recent studies have suggested that stroma-related signatures could predict anthracycline resistance, and increased expression of tissue inhibitor of metalloproteinases 1 (TIMP1) has also been implicated in resistance. Deficiency of the BRCA1 and BRCA2 genes may render cells more sensitive to topoisomerase inhibitors such as anthracyclines by disrupting repair of damaged DNA. Chromosome 17 polysomy has also been associated with increased responsiveness to anthracyclines. Given the complexity of topoisomerases and DNA repair pathways, it may be that a multifactorial approach, rather than reliance on a single biomarker, is needed to identify anthracycline-sensitive patients.

Keywords:  Anthracyclines , Breast cancer , Drug response biomarkers , HER2 , Topoisomerase II alpha

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PII: S1359-6349(11)70005-2

doi:10.1016/S1359-6349(11)70005-2

EJC Supplements
Volume 9, Issue 2 , Pages 16-21, October 2011

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