Encouraging results from validation study of trial of personalized treatment in breast cancer

The overall performance of the gene signature to be used in the first large-scale trial to study the role of such tumor signatures in breast cancer is encouraging and gives the green light to start the trial proper, Dr. Martine Piccart, head of the medical oncology department at the Institut Jules Bordet in Brussels, Belgium, told the San Antonio Breast Cancer conference today (Wednesday 8 December 2004). Dr Piccart heads the TRANSBIG consortium, which intends to use the 70-gene prognostic signature developed by the Netherlands Cancer Institute / Antoni van Leeuwenhoek Hospital (NKI-AVL) in MINDACT, a large, prospective, international randomized clinical trial for lymph node negative breast cancer that will look at the utility of the signature in clinical practice.

TRANSBIG is a translational research network involving 39 partners from all over Europe and Latin America. The validation involved centers in France, Sweden, UK and the US and was based on the frozen archival tumor material of 291 node negative (without cancerous cells in the lymph nodes) patients aged < 60, diagnosed through 1998, and who had received only surgery or radiotherapy. The 70-gene signature outperformed existing standard criteria (St. Gallen, Nottingham Prognostic Index, and Adjuvant Online) in predicting time to distant metastasis (the development of tumors in other parts of the body) and overall survival. The statistical analysis was carried out independently of Amsterdam by a statistical team in Belgium, in collaboration with a bioinformatics group in Switzerland. Dr.Piccart said: "While the overall performance of the 70-gene prognostic signature in the external validation series was inferior to the original Amsterdam series, the results are more than good enough to justify starting the trial." If the trial confirms that the signature is better than standard methods are in determining which women need chemotherapy after their breast cancer has been surgically removed, it is expected that prescription of such treatment can be reduced by up to 20%. This could have substantial impact on the overall quality of life for many women with breast cancer by reducing side effects, and also the associated health care costs. “We are very excited that we may have a chance to reduce over-treatment in early breast cancer”, said Dr. Piccart. ” We are looking forward to starting the trial in late 2005″.