Monitoring of serum Her-2/neu predicts response and progression-free survival to trastuzumab-based treatment in patients with metastatic breast cancer.
OBJECTIVE
The present pilot study was performed to elucidate whether early changes in serum Her-2/neu extracellular domain (ECD) levels during trastuzumab-based treatment would predict the clinical course of disease in patients with metastatic breast cancer.


METHODS
Sera from 55 patients with Her-2/neu-overexpressing metastatic breast cancer obtained immediately before each weekly administration of trastuzumab were analyzed by a serum Her-2/neu ELISA.


RESULTS
Whereas response rates were significantly higher in patients with elevated (>or=15 ng/ml) ECD levels before initiation of treatment (35% versus 7%, P = 0.045), progression-free and overall survival did not differ significantly between patients with normal and elevated ECD levels. In patients responding to treatment, ECD levels decreased significantly as early as from day 8 of treatment onwards (all P for weekly measurements versus baseline <0.001). In contrast, no significant change in ECD levels was observed in patients with progressive disease. Multiple logistic regression analyses identified kinetics of ECD levels as the only factor that allowed for the accurate prediction of response likelihood as early as from day 8 of trastuzumab-based treatment onwards (P = 0.020). In addition, determination of serial ECD levels allowed for the prediction of the risk for disease progression within the observed period as early as day 15 of treatment (P = 0.010).


CONCLUSIONS
Serial monitoring of the ECD may represent a valuable tool for early prediction of the probability of response and progression-free survival to trastuzumab-based treatment and is thus likely to contribute to an optimization of treatment and resource allocation.
Köstler
Wolfgang J
WJ
Department of Medicine I, University Hospital of Vienna, Austria. wolfgamg.koestler@akh-wien.ac.at
Schwab
Barbara
B
Singer
Christian F
CF
Neumann
Rainer
R
Rücklinger
Ernst
E
Brodowicz
Thomas
T
Tomek
Sandra
S
Niedermayr
Monika
M
Hejna
Michael
M
Steger
Günther G
GG
Krainer
Michael
M
Wiltschke
Christoph
C
Zielinski
Christoph C
CC
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018567:Breast Neoplasms, Male / Q000188:drug therapy / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D004784:Environmental Monitoring / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D011336:Probability; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood*; D013997:Time Factors; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab