TY - JOUR
TI - Combination of osteopontin and activated leukocyte cell adhesion molecule as potent prognostic discriminators in HER2- and ER-negative breast cancer
AU - Ihnen, M.
AU - Wirtz, R.M.
AU - Kalogeras, K.T.
AU - Milde-Langosch, K.
AU - Schmidt, M.
AU - Witzel, I.
AU - Eleftheraki, A.G.
AU - Papadimitriou, C.
AU - Jänicke, F.
AU - Briassoulis, E.
AU - Pectasides, D.
AU - Rody, A.
AU - Fountzilas, G.
AU - Müller, V.
JO - British Journal of Cancer
PY - 2010
VL - 103
TODO - 7
SP - 1048-1056
PB - 
SN - 0007-0920, 1532-1827
TODO - 10.1038/sj.bjc.6605840
TODO - activated leukocyte cell adhesion molecule;  epidermal growth factor receptor 2;  estrogen receptor alpha;  messenger RNA;  osteopontin;  activated leukocyte cell adhesion molecule;  EIF3A protein, human;  epidermal growth factor receptor 2;  estrogen receptor;  initiation factor 3;  messenger RNA;  osteopontin, adult;  aged;  article;  breast cancer;  cluster analysis;  controlled study;  disease free survival;  female;  high risk population;  human;  human tissue;  major clinical study;  microarray analysis;  overall survival;  priority journal;  prognosis;  reverse transcription polymerase chain reaction;  breast tumor;  decision tree;  DNA microarray;  genetics;  metabolism;  middle aged;  mortality;  risk, Activated-Leukocyte Cell Adhesion Molecule;  Adult;  Aged;  Breast Neoplasms;  Cluster Analysis;  Decision Trees;  Disease-Free Survival;  Eukaryotic Initiation Factor-3;  Female;  Humans;  Middle Aged;  Oligonucleotide Array Sequence Analysis;  Osteopontin;  Prognosis;  Receptor, erbB-2;  Receptors, Estrogen;  Risk;  RNA, Messenger, Activated-Leukocyte Cell Adhesion Molecule;  Adult;  Aged;  Breast Neoplasms;  Cluster Analysis;  Decision Trees;  Disease-Free Survival;  Eukaryotic Initiation Factor-3;  Female;  Humans;  Middle Aged;  Oligonucleotide Array Sequence Analysis;  Osteopontin;  Prognosis;  Receptor, ErbB-2;  Receptors, Estrogen;  Risk;  RNA, Messenger
TODO - Background:To analyse the discriminative impact of osteopontin (OPN) and activated leukocyte cell adhesion molecule (ALCAM), combined with human epidermal growth factor 2 (HER2) and oestrogen receptor (ER) in breast cancer.Methods:Osteopontin, ALCAM, HER2 and ER mRNA expression in breast cancer tissues of 481 patients were analysed (mRNA microarray analysis, kinetic RT-PCR). Hierarchical clustering was performed in training cohort A (N100, adjuvant treatment) and validation cohorts B (N200, no adjuvant treatment, low-risk) and C (N181, adjuvant treatment, high-risk).Results:Negative/low ER and HER2, high OPN and low ALCAM mRNA expression helped to identify patients at particularly high risk, showing shorter DFS, P0.001, and OAS, P0.001. Although both validation cohorts showed diverse risk and treatment profiles, this marker constellation was concordantly associated with shorter DFS and OAS (P0.001 and P0.075 for cohort B and P0.043 and P0.001 for cohort C, respectively). In multivariate analysis, this algorithm was the main independent prognostic factor. Cohort B: DFS, P0.0065, OAS, not significant; cohort C: DFS, P0.026, OAS, P0.001.Conclusion:Activated leukocyte cell adhesion molecule and OPN mRNA expression has a strong discriminative impact on survival within cancer patients with low or negative expression of ER and HER2, so called high-risk breast cancers, and might help in identifying patients who could benefit from new treatment approaches like targeted therapies in the adjuvant setting. © 2010 Cancer Research UK. All rights reserved.
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