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Molecular prediction of tamoxifen resistance in breast cancer

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Background

Estrogen receptor (ER) alpha-positive breast cancer patients are commonly treated with tamoxifen, a potent and widely used anti-estrogen. However, only one-half of the recurrences of ER-positive breast tumors respond to tamoxifen while the other half is resistant [1]. The ability to accurately predict tamoxifen treatment outcome would therefore significantly advance the management of breast cancer. The aim of the current project is to identify a gene expression profile associated with tamoxifen resistance using microarray analysis.

Patients and methods

To identify gene expression patterns that might predict response to tamoxifen, 90 breast cancer patients were selected for whom fresh frozen tissue was available. All these patients had received surgery with or without radiotherapy for primary breast cancer, while none had received adjuvant systemic treatment. All patients developed metastatic disease and were subsequently treated with tamoxifen. Response was mainly determined radiographically [2]. Approximately 40% of these patients had CR/PR or clinical benefit during less than 6 months and are defined as tamoxifen resistant, whereas the remaining 60% are defined as tamoxifen sensitive (CR/PR or clinical benefit for more than 6 months). Of the latter group, 17 out of 54 even showed no progression for at least 2 years.

Gene expression profiling was performed using 44K oligo microarrays. Data analysis is ongoing and results will be presented at the MBBC symposium.

Future directions

A validation set will be analyzed to confirm our initial findings. Furthermore, we will test whether this profile can also be used in the adjuvant setting. In addition, we will evaluate the combination of microarray analysis and targets identified by RNAi screens in vitro in determining diagnostic tools for prediction of therapy outcome.

References

  1. 1.

    Pritchard KI: Endocrine therapy of advanced disease: analysis and implications of the existing data. Clin Cancer Res. 2003, 9: 460S-467S.

  2. 2.

    Hayward JL, Carbone PP, Heuson JC, Kumaoka S, Segaloff A, Rubens RD: Assessment of response to therapy in advanced breast cancer: a project of the Programme on Clinical Oncology of the International Union Against Cancer, Geneva, Switzerland. Cancer. 1977, 39: 1289-1294.

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Kok, M., van den Berg, T., Delahaye, L. et al. Molecular prediction of tamoxifen resistance in breast cancer. Breast Cancer Res 7, P2.07 (2005) doi:10.1186/bcr1118

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Keywords

  • Breast Cancer
  • Tamoxifen
  • Breast Cancer Patient
  • Gene Expression Profile
  • Microarray Analysis