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Old 12-16-2004, 10:04 PM   #1
Merridithp
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By Thomas S. May

December 11, 2004 — Combining the 70-gene Prognosis Profile with the recently developed Wound Response Signature, can significantly improve the clinical capacity for predicting outcome in breast cancer, according to a study presented at the 27th San Antonio Breast Cancer Symposium.

Through gene expression analysis, the 70-gene prognostic signature can identify breast cancer patients at high risk for developing distant metastases. However, approximately 50% of patients classified as high-risk do not develop metastases. Several other recently developed profiles, including the Wound Response Signature and Intrinsic Gene Set, show promise in further refining prognostic tools.

To investigate whether combining the 70-gene Prognosis Profile with the Wound Response Signature can improve the accuracy of clinical prediction, a group of scientists led by Dimitry Nuyten, MD, of The Netherlands Cancer Institute in Amsterdam, analyzed 295 stage 1 and 2 breast carcinomas from cancer patients. All patients were diagnosed and treated between 1984 and 1995, with a median follow-up of 7.8 years. The individual prognostic value of the Wound Response Signature gene expression profile was also evaluated.

All tumors previously assessed with the 70-gene prognostic profile, were re-analyzed and categorized according to Wound Response Signature. The Wound Response Signature identified 126 tumors as positive or "activated," while 169 were identified as negative or "quiescent."

Patients with Wound Signature-negative tumors had a 75% probability of metastasis-free survival at 10 years, compared with a 50% probability for those with activated tumors (P < .00001). Wound Signature demonstrated even greater predictive value for overall survival, with10-year overall survival of 84% for patients with quiescent tumors compared with 51% for patients with Wound Signature-positive tumors (P< .00001). According to multivariate survival analysis, positive Wound Signature characterization is more predictive of death than several other factors, including tumor grade (hazard ratio 3.657; 95% confidence interval 1.453-9.208, P = .006)

Patients meeting high-risk criteria for both the 70-gene prognostic profile and the Wound Response Signature had a significantly greater risk of developing metastases than patients meeting only the 70-gene profile risk criteria (P < .00001). Further studies are needed to determine the benefit of combining these 2 profiles in the clinical areana.

According to the investigators, these data validate the Wound Response Signature's predictive capacity and confirm the hypothesis that combining the 70-gene prognostic profile with the Wound Response Signature improves risk stratification.

http://clinicaloptions.com/onco/news/news_SABCS_36.asp
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