Test for gene expression optimizes therapy planning

AMSTERDAM, The Netherlands, February 19, 2008 / Agendia BV, Breast cancer is the most common cancer in women worldwide. If breast cancer is diagnosed at an early stage, the survival rate is currently over 70 percent. However, about 30 percent of stage I and II breast cancer patients develop metastases within five to ten years. These women with high risk of breast cancer recurrence must be identified early on and receive specific adjuvant treatment. This is the unanimous opinion of experts communicated at the Agendia press conference in Berlin on the occasion of the 28th German Cancer Congress. A new procedure makes the accurate determination of the risk of relapse in breast cancer possible by measuring the gene expression (gene activity) of a tumor tissue sample. The precise classification of the relapse risk as high or low offers a well-founded basis for therapy decisions by the physician. Early in 2007, with Agendia´s MammaPrint®, the U.S. Food and Drug Administration (FDA) cleared a gene expression test for the prognosis of breast cancer for the very first time. As one of the world leaders in the development of molecular diagnostic procedures for decoding tumor diseases, Agendia’s foremost objective is to improve the quality of life for cancer patients. Reliable prognoses help the physician to adapt treatment to the patient’s needs even more effectively. “With this, Agendia is laying the foundation for personalized treatment,” said Dr. Bernhard Sixt, CEO of Agendia BV, in Berlin.

“More than 55,000 women are newly diagnosed with breast cancer every year in Germany; this is more than 150 women per day.” These were the frightening figures with which Professor Gerhard Seitz, Chief Physician of the Institute of Pathology at the Clinical Center of Bamberg started his lecture. However, thanks to the progress of medicine, the survival rate of the women affected has improved significantly in the last few years. A large proportion of those affected can already be cured by surgical removal of the tumor. A small fraction suffers a relapse and requires adjuvant hormone treatment and chemotherapy to possibly prevent or at least slow down the progression of the disease. “All the research efforts by scientific societies therefore have a common goal: the avoidance of overtreatment,” said Seitz. “Current therapy recommendations laid down at the St. Gallen conference or even the S3 Guideline of the German Cancer Society are of limited help,” Seitz went on to explain. According to references in the literature, up to 85% of the women receive chemotherapy. However, the 10-year survival rate is only improved by 3 to 5 percent. Seitz summarized: “It must therefore be our goal to find new prognostic factors allowing reliable predictions as to who can be spared chemotherapy without affecting the chances of survival.”

Gene expression as a new approach in cancer prognosis
By measuring the gene expression of tumor cells, predictions can be made as to the individual risk of recurrence. “Each tumor has molecular mechanisms at an early stage that determine its individual development,” explained Dr. Iris Simon of Agendia BV. With the help of DNA microarray, a gene expression profile of a tumor tissue sample is constructed that accurately classifies the tumor. With MammaPrint, Agendia has developed an in vitro diagnostic method that reliably assesses the risk of metastization in breast cancer. For the analysis, the company provides the physician with a test kit containing an RNA-stabilizing solution (RNARetain® solution). A sample of freshly collected tissue, unfixed and uncooled, can thus be sent to Agendia. The RNA-stabilizing solution ensures both convenient transport and the qualitative preservation of the sample without degrading the target RNA molecule. Within ten days the physician receives the test result that clearly classifies the individual risk of metastization as high or low. The result thus provides a well-founded basis for the doctor’s treatment decision. Reliability proven in studies In the meantime, MammaPrint has been validatedi in more than 1,000 tests within the scope of clinical studies. With more than 12,000 tests conducted so far, the technical robustness and reliability of MammaPrint for routine clinical assays is well-established. The risk of relapse is reliably assessed as high or low for each individual patient. The high degree of reliability prompted the FDA to clear MammaPrint as the first test of its kind in early 2007. In Europe, there is no equivalent clearance procedure for diagnostic tests. However, since June 2005, Agendia Laboratories have been ISO-17025 certified. In addition, MammaPrint declares the CE-marking and thus fulfills all the quality requirements of the European Union. The Time Magazine honored MammaPrint as one of the best inventions of 2007.

An important milestone in breast cancer prognosis
“The determination of the gene expression of a tumor such as with MammaPrint is an important milestone on the way to sparing low-risk patients the stress and risks of chemotherapy,” explained Dr. Georg Kunz, Chief Physician of the Gynecological Clinic and Director of the Breast Center at St. Johannes Hospital in Dortmund. “The present scientific studies confirm the reliability of MammaPrint in accurately predicting the individual risk of recurrence in women with breast cancer.” With the use of MammaPrint, breast cancer patients can receive a more targeted treatment. This can help avoid stressful therapies and improve the quality of life for patients. Even from an economic point of view, MammaPrint can be rated positively. “Thanks to MammaPrint, up to 30 percent of the costs for chemotherapy can be saved,” said Kunz. And of course the benefit for the patient herself who is spared chemotherapy must also not be forgotten. “The statements by the expert panels of important international breast cancer conferences leave no doubt about the fact that MammaPrint will establish itself as an integral part of the risk stratification for breast cancer,” said Kunz.

The future of cancer prognosis – Tests for other cancer indications
The determination of gene expression is not only applicable for breast cancer. Dr. Simon presented the latest study results on the validation of a test for determining gene expression in colorectal cancer. Colorectal cancer is the third most common type of cancer worldwide after lung and breast cancer: in Europe alone, about 140,000 cases of the disease are newly diagnosed every year. Although in most patients the tumor can be surgically removed, the recurrence rate is over 50 percent within the first 24 months. Reliably classifying patients into high-risk and low-risk groups is difficult since clinical factors such as the degree of tumor´s malignancy or the number of lymph nodes examined provide only an inaccurate prognosis.

With ColoPrint, Agendia has developed a prognostic profile that makes it possible to predict the individual course of stage II colorectal cancer. 600 patients from various countries in Europe and the United States are currently being recruited for a prospective clinical study to better compare the risk assessment between ColoPrint® and conventional clinical parameters. In the future, patients with stage II colorectal cancer will be able to benefit from the widespread use of such a test since high-risk stage II patients in particular are currently not identified early enough.

In the future, the determination of gene expression will help physicians in patient-specific therapy planning for other cancers as well, since reliable predictions on the individual course of tumor diseases can be provided on the basis of gene expression profiles.

About Agendia
Agendia is a leading innovative company in the development of molecular diagnostic procedures for cancer based on modern DNA microarray technology. Agendia performs in vitro laboratory tests providing information on individual tumor properties on the basis of cancer-type specific gene expression profiles. This is how the risk of metastases, for instance, can be determined. The results of the analysis assist the physician in making well-founded and individualized therapy decisions for the benefit of his or her patient. Agendia thus contributes to improving the quality of life for cancer patients. MammaPrint® determines the individual recurrence risk in breast cancer patients. With CupPrint®, Agendia offers physicians a test for identifying the primary tumor in cancers of unknown origin (CUP). In addition, Agendia is continuously working on the development of further tests for establishing prognostic and predictive gene expression profiles. The Amsterdam based company was founded in 2003.

You can find more information on the Internet at www.agendia.com.

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