BERLIN, Germany, May 17, 2005 (PRIMEZONE) -- Epigenomics AG (Frankfurt, Prime Standard: ECX), today revealed data confirming that its proprietary DNA methylation markers are closely correlated with disease recurrence and prediction of therapy response in early breast cancer. Specific DNA methylation markers, including PITX2, will be incorporated into a test that will provide physicians with clinically relevant information that may spare approximately half of estrogen-dependent, node-negative breast cancer patients from going through the discomfort and side effects of chemotherapy. Currently, combined chemotherapy and endocrine therapy with drugs such as Tamoxifen is recommended as the treatment of choice for most breast cancer patients to prevent the disease from returning. However, a large proportion of patients treated with endocrine therapy alone have an excellent prognosis after 10 years and therefore do not need the additional chemotherapy. The data from the study which was presented at the 41st Annual Meeting of the American Society of Clinical Oncology (May 14-17, Orlando, Florida, USA) validate the role of the DNA methylation markers in identifying this group of patients. In addition, data were published in the journal Cancer Research which describe the identification of markers for tamoxifen response in advanced breast cancer, further underlining the importance of DNA methylation for this disease.
"The results of these studies are a major step forward for the team at Epigenomics and our clinical collaborators. Together with our previous studies, we have now confirmed the strong correlation of PITX2 with disease recurrence in over 1000 breast patients from four different studies," noted Alexander Olek Ph.D., Chief Executive Officer of Epigenomics. "Due to the excellent clinical performance in all studies we have conducted so far and the fact that the marker can be reliably measured in paraffin-embedded tissue, we are confident that our tissue-based tests incorporating these and other specific DNA methylation markers will become a very valuable tools for oncologists to help them guide adjuvant therapy with tamoxifen and potentially other endocrine based therapies, and/or chemotherapy in breast cancer."
At ASCO, Epigenomics and its collaborators presented results from a large, multi-center clinical study validating the DNA methylation marker PITX2 for predicting outcome in tamoxifen-treated, hormone receptor positive, node-negative, breast cancer patients. Currently, combined chemotherapy and endocrine therapy is recommended as the treatment of choice for most of the patients with lymph node negative, hormone receptor positive disease. However endocrine therapy alone may be sufficient for many of them in view of their excellent prognosis. The presented data suggest that DNA methylation of PITX2 could be used as a guide to spare unnecessary and thus potentially harmful chemotherapy for many of these patients.
Epigenomics and its collaborators had originally identified and validated PITX2 methylation as a predictor for disease recurrence in breast cancer in two smaller studies using Epigenomics' microarray technology. Based on results from these studies, a real-time PCR based quantitative methylation assay (QM) has been developed to measure PITX2 methylation on routinely obtained paraffin-embedded tumor tissue. Results from matched pairs of frozen and archived specimens indicated that the assay works well on paraffin-embedded material. Furthermore, performance on these archived specimens was highly reproducible, and little variation from section to section was seen.
In the current multi-center study, this PITX2 methylation assay was used to analyze paraffin-embedded tumors of 422 node-negative patients from nine clinical centers in Europe and the US who were treated with tamoxifen alone. None of the patients had been included in the prior studies. Successful methylation measurements were obtained in 95.8% of the cases (411 patients). As in the prior studies, PITX2 methylation was strongly correlated with outcome (Cox proportional hazard model, p=0.025). In the group with low PITX2 methylation (45% of the cohort), 98% of the patients were metastasis-free after 10 years, compared to only 85% in the group with high PITX2 methylation. In a multivariate model, PITX2 methylation added significant information to conventional factors such as grade and age.
"Our results provide substantial evidence that DNA methylation is suitable for routine clinical use in order to predict outcome in node-negative, tamoxifen-treated patients and to identify a large number of low-risk patients who can be spared the burden of additional cytotoxic therapy," stated Prof. Dr. med. Nadia Harbeck, Associate Professor of Obstetrics and Gynecology, Technical University of Munich, Germany, who presented the results at the ASCO meeting. "The fact that methylation was measured on routinely available paraffin-embedded sections and that outcome prediction is achieved with only one marker, will greatly facilitate the integration of DNA methylation into clinical routine."
The study forms the basis of a research and product development program Epigenomics is conducting in a partnership with Roche Diagnostics. The program is currently scheduled to enter large scale clinical evaluation with Roche Diagnostics in the third quarter 2005.
At the same time, results from an independent study in advanced breast cancer were published in the journal Cancer Research, showing that DNA methylation markers are also strong outcome predictors in patients treated with tamoxifen for advanced disease. In this study, Epigenomics and clinical collaborators from Erasmus Medical Center (Netherlands) and Dept. of OB&GYN, Technical University of Munich (Germany) used a microarray based technology to determine the DNA methylation status of 117 candidate genes in a cohort of 200 steroid hormone receptor-positive tumors of patients who received tamoxifen as first-line treatment for recurrent breast cancer.
Of the genes analyzed, the methylation status of 10 genes was significantly associated with clinical outcome of tamoxifen therapy. Hypermethylation of phosphoserine aminotransferase (PSAT1) was the strongest single marker predictor of clinical outcome. Although these markers seem to be more relevant for metastatic disease and therefore will not be included in the final panel, the results further underline the importance of DNA methylation in breast cancer.
About Breast Cancer Treatment
Treatment of breast cancer is currently determined according to an individualized assessment based on specific classes of risk. Most patients undergo surgery plus some form of adjuvant treatment to prevent the disease returning. This adjuvant treatment is based on nodal status (spread to the axillary lymph glands) and hormone receptor status (response to endocrine therapy). About half of all breast cancer patients (213,000 women in the US and 251,000 women in Europe) ) are lymphnode-negative and hormone receptor positive. This means that post-surgery, the disease of a large number of these women could be controlled by endocrine therapy alone thereby avoiding potentially very toxic chemotherapy. Unfortunately at present, this low-risk patient population is difficult to identify, so most patients will receive chemotherapy anyway, even though only a small proportion really require it.
About Epigenomics' Breast Cancer Outcome Prediction Test Epigenomics' breast cancer outcome prediction test is being developed to provide physicians with clinically useful information to support the decision on whether a breast cancer patient needs more aggressive treatment involving chemotherapy or whether endocrine therapy alone will be sufficient. The test could be conducted at any local reference laboratory, utilizing paraffin-embeded tissue samples that are routinely taken at biopsy.
Data from multiple studies show that the DNA methylation markers identified by Epigenomics can be used to more accurately divide breast cancer patients into two risk groups: patients with good outcome after tamoxifen therapy alone; and patients who are at a high-risk of disease recurrence if treated with tamoxifen therapy alone. In addition, recently published data suggest that the markers may also be used for predicting recurrence in breast cancer independent of therapy, thereby making it likely that the markers also work for newer endocrine treatments.
About Epigenomics
Epigenomics is a molecular diagnostics company with a focus on the development of novel products for cancer. By detecting and interpreting DNA methylation patterns, Epigenomics' tests can potentially diagnose disease at an early stage and help guide physicians to select an appropriate therapy. Epigenomics collaborates with Roche Diagnostics on the development of several diagnostic products in cancer. The company has its headquarters in Berlin, Germany, and a wholly owned subsidiary in Seattle, USA. For more information, please visit our website at www.epigenomics.com.
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-0- Epigenomics AG Oliver Schacht (Finanzvorstand) Hong Thieu (VP Corporate Affairs & IR) Sabine Maier (Medical Manager) +49 (0) 30 24345-0 Halsin Partners Mike Sinclair +44 (0) 870 747 0880