Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 22, No 14S (July 15 Supplement), 2004: 525
© 2004 American Society of Clinical Oncology

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Abstract

DNA methylation profile predicts risk of recurrence in tamoxifen-treated, node-negative breast cancer patients

Epigenomics AG, Berlin, Germany; Stiftung Tumorbank, Basel, Switzerland; University Hospital Eppendorf, Hamburg, Germany; National Cancer Institute, Bari, Italy; Centre René Huguenin, St. Cloud, France; Erasmus Medical Center, Rotterdam, Netherlands; Technical University, Munich, Germany

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Background: Today, many women with node-negative, hormone receptor positive breast cancer receive adjuvant chemotherapy followed by endocrine therapy. However, the majority of these patients would never have experienced a relapse and would have been sufficiently treated with endocrine therapy alone. Aim of our study was to identify DNA methylation markers associated with a low risk of recurrence after tamoxifen monotherapy. Methods: As a first step, we performed a genome-wide screening for DNA methylation markers associated with the risk of recurrence after tamoxifen monotherapy. The best candidates were then validated in a population of 278 patients using a microarray approach. Results: We identified several DNA methylation markers with a strong relation to clinical outcome (cox proportional hazard model, p<0.05). In a multivariate model, DNA methylation contributed significant information to conventional factors such as grade, tumor size, or estrogen receptor expression level. Furthermore, by combining three markers into a methylation score and defining a cut-off, we identified a group with excellent outcome when treated with tamoxifen alone (disease-free survival 95 % at 10 years, versus 62 % in the poor prognosis group). Validation in an independent patient cohort is currently in progress. So far, the best marker has already been validated (p<0.05). Conclusions: These results provide substantial evidence that DNA methylation could be used to predict outcome in node-negative patients with tamoxifen monotherapy, and to identify low risk groups which may not require additional cytotoxic treatment.

Author Disclosure

Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Epigenomics AG Epigenomics AG Epigenomics AG Epigenomics AG Epigenomics AG

Abstract presentation from the 2004 ASCO Annual Meeting