VIENNA (Reuters Health) - Dutch researchers have developed a 76-gene prognostic profiling tool that predicts prognosis of lymph node-negative (LNN) breast cancer patients with more than 90% accuracy in internal tests.
The tool is designed to define which LNN women are most likely to be cured by primary surgery alone versus those at risk for relapse, and development of distant metastases within 5 years, regardless of age, tumor size and grade. At present, nearly 80% of such women are candidates for adjuvant endocrine and/or chemotherapy after surgery.
Yet, 60% to 70% would have been cured by surgery alone, though there is no way to identify them, researchers said.
At a press briefing at the 29th European Society of Medical Oncology Congress, Dr. Jan G. Klijn, head of the Division of Endocrine Oncology at the Daniel den Hoed Cancer Center and the Erasmus University Medical Center in Rotterdam, said the signature identified patients that eventually would develop metastases with more than 90% accuracy, and could have reduced by 30% to 40% patients who would have received the adjuvant therapy.
Less than 10% of signature profiling results generated false positives, but it had a specificity of only 50%; many patients still had poor prognosis, even if they did not develop metastases.
In addition, in the course of the research, scientists detected genes of unknown function that may be used to develop new treatments.
He and his colleagues used a microarray technique to test 20,000 to 30,000 genes together to analyze total tumor RNA samples from 286 LNN breast cancer patients who had not received any adjuvant system treatment. Then using a training group of 115 patients, they identified the 76-gene signature. It was then tested on an independent set of 171 LNN patients, on whom it was successfully validated with 93% sensitivity.
The results of the gene signature are currently undergoing confirmation testing in a multicenter study.
The gene signature profile system is at least the second such effort aimed at developing such a prognostic method for breast cancer.
A 70-gene signature, the so-called Amsterdam signature appears to have a similar power, though it has prognostic value in women under 55 years old, Dr. Klijn said in the briefing. “Our profile has value in all age groups.” This earlier effort was developed by Rene Bernards, Ph.D, of Netherlands Cancer Institute, in Amsterdam, and his colleagues.
Also, of the 70 genes in the Amsterdam signature, only three overlap with the Rotterdam signature developed by Dr. Klijn and his colleagues. Still, he said, it is likely that while the genes may be different, they still represent the same or very similar gene-protein pathways.
MeSH Headings:Chromosome Mapping: Genetic Techniques: Investigative Techniques: Analytical, Diagnostic and Therapeutic Techniques and EquipmentCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
