A prospective evaluation of a breast cancer prognosis signature in the observational RASTER study.
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 the 70-gene signature low-risk patients received adjuvant chemotherapy (ACT) versus 81% (169/208) of the 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 clinicopathological 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.
Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
C A
CA
Drukker
J M
JM
Bueno-de-Mesquita
V P
VP
Retèl
W H
WH
van Harten
H
H
van Tinteren
J
J
Wesseling
R M H
RM
Roumen
M
M
Knauer
L J
LJ
van 't Veer
G S
GS
Sonke
E J T
EJ
Rutgers
M J
MJ
van de Vijver
S C
SC
Linn
D000328:Adult; D001943:Breast Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D011336:Probability; D011446:Prospective Studies; D015996:Survival Rate