TY - JOUR
T1 - Predictive markers of anthracycline benefit: a prospectively planned analysis of the UK National Epirubicin Adjuvant Trial (NEAT/BR9601)
AU - Bartlett, JMS
AU - Munro, AF
AU - Dunn, JA
AU - McConkey, C
AU - Jordan, SC
AU - Twelves, CJ
AU - Cameron, DA
AU - Thomas, J
AU - Campbell, FM
AU - Rea, Daniel
AU - Provenzano, E
AU - Caldas, C
AU - Pharaoh, P
AU - Hiller, L
AU - Earl, H
AU - Poole, CJ
PY - 2010/3/1
Y1 - 2010/3/1
N2 - Background The NEAT/BR9601 trial showed benefit for addition of anthracyclines to cyclophosphamide, methotrexate, and fluorouracil (CMF) as adjuvant treatment for early breast cancer. We investigated prospectively predictive biomarkers of anthracycline benefit including HER2 and TOP2A.
Methods 1941 tumours from 2391 women recruited to NEAT/BR9601 were analysed on tissue microarrays for HER2 and TOM amplification and deletion, HER1-3 and Ki67 expression, and duplication of chromosome 17 centromere enumeration probe (Ch17CEP). Log-rank analyses identified factors affecting relapse-free and overall survival, and regression models tested independent prognostic effect of markers, with adjustment for known prognostic factors (age, nodal status, oestrogen-receptor status, grade, and tumour size). The predictive value of markers was tested by treatment interactions for relapse-free and overall survival.
Findings 1762 patients were analysed. 21% of tumours (n=367) were HER2 amplified, 10% were TOP2A amplified (n=169), 11% showed TOP2A deleted (n=191), 23% showed Ch17CEP duplication (n=406), and 61% had high (>13.0%) Ki67 (n=1136). In univariate analyses, only HER2 amplification and TPO2A deletion were significant prognostic factors for relapse-free (hazard ratio [HR] 1.59, 95% CI 1.32-1.92, p
AB - Background The NEAT/BR9601 trial showed benefit for addition of anthracyclines to cyclophosphamide, methotrexate, and fluorouracil (CMF) as adjuvant treatment for early breast cancer. We investigated prospectively predictive biomarkers of anthracycline benefit including HER2 and TOP2A.
Methods 1941 tumours from 2391 women recruited to NEAT/BR9601 were analysed on tissue microarrays for HER2 and TOM amplification and deletion, HER1-3 and Ki67 expression, and duplication of chromosome 17 centromere enumeration probe (Ch17CEP). Log-rank analyses identified factors affecting relapse-free and overall survival, and regression models tested independent prognostic effect of markers, with adjustment for known prognostic factors (age, nodal status, oestrogen-receptor status, grade, and tumour size). The predictive value of markers was tested by treatment interactions for relapse-free and overall survival.
Findings 1762 patients were analysed. 21% of tumours (n=367) were HER2 amplified, 10% were TOP2A amplified (n=169), 11% showed TOP2A deleted (n=191), 23% showed Ch17CEP duplication (n=406), and 61% had high (>13.0%) Ki67 (n=1136). In univariate analyses, only HER2 amplification and TPO2A deletion were significant prognostic factors for relapse-free (hazard ratio [HR] 1.59, 95% CI 1.32-1.92, p
U2 - 10.1016/S1470-2045(10)70006-1
DO - 10.1016/S1470-2045(10)70006-1
M3 - Article
C2 - 20079691
VL - 11
SP - 266
EP - 274
JO - The Lancet Oncology
JF - The Lancet Oncology
IS - 3
ER -
