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Wiley, International Journal of Cancer, 4(133), p. 929-936, 2013

DOI: 10.1002/ijc.28082

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A prospective evaluation of a breast cancer prognosis signature in the observational RASTER study

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

The 70-gene signature (MammaPrint™) has been developed on retrospective series of breast cancer patients to predict the risk of breast cancer distant metastases. The microarRAy-prognoSTics-in-breast-cancER (RASTER) study was the first study designed to prospectively evaluate the performance of the 70-gene signature, which result was available for 427 patients (cT1-3N0M0). Adjuvant systemic treatment decisions were based on the Dutch CBO 2004 guidelines, the 70-gene signature, and doctors' and patients' preferences. Five-year distant-recurrence-free-interval (DRFI) probabilities were compared between subgroups based on the 70-gene signature and Adjuvant! Online (AOL) (10-year survival probability <90% was defined as high-risk). Median follow-up was 61.6 months. Fifteen percent (33/219) of 70-gene signature low-risk patients received adjuvant chemotherapy (ACT) versus 81% (169/208) of 70-gene signature high-risk patients. The 5-year DRFI probabilities for 70-gene signature low-risk (n=219) and high-risk (n=208) patients were 97·0% and 91·7%. The 5-year DRFI probabilities for AOL low-risk (n=132) and high-risk (n=295) patients were 96·7% and 93·4%. For 70-gene signature low-risk - AOL high-risk patients (n=124), of whom 76% (n=94) had not received ACT, 5-year DRFI was 98.4%. In the AOL high-risk group, 32% (94/295) less patients would be eligible to receive ACT if the 70-gene signature was used. In this prospective community-based observational study, the 5-year DRFI probabilities confirmed the additional prognostic value of the 70-gene signature to clinic-pathological risk estimations such as AOL. Omission of adjuvant chemotherapy as judged appropriate by doctors and patients and instigated by a low-risk 70-gene signature result, appeared not to compromise outcome.