Prognostic and predictive impact of the HER-2/ neu extracellular domain (ECD) in the serum of patients treated with chemotherapy for metastatic breast cancer.
BACKGROUND
The extracellular domain of the HER-2/neu -receptor (ECD) is shed from the receptor protein and can be detected in serum. However, the clinical implication of HER-2/neu ECD measurement must be further evaluated.


METHODS
In patients with metastatic breast cancer participating in a trial on first-line chemotherapy, the association of serum HER-2/neu ECD with progression-free interval, survival, and response was studied. Blood samples of patients receiving epirubicin and either cyclophosphamide (EC) or paclitaxel (ET) were collected before (n = 103) and in addition, after three courses of therapy (n = 46).


RESULTS
HER-2/neu ECD levels correlate with HER-2/neu overexpression of corresponding primary tumors determined by immunohistochemistry (antibody CB11, p = 0.018) with an optimized cut-off at 15 ng/mL. Elevated serum levels of HER-2/neu ECD before chemotherapy were correlated with shorter overall survival (p = 0.0097), but not with reduced progression-free survival and response to chemotherapy. In subgroup analyses, patients with elevated pretherapeutic HER-2/neu ECD levels treated with EC showed shorter overall survival (p = 0.0092); no difference was seen in the ET group. With regard to progression-free survival, patients with elevated HER-2/neu ECD levels tended to benefit from ET (p = 0.0341), in patients with low levels no difference was observed between EC and ET. A decrease of HER-2/neu ECD levels after three courses of therapy was associated with response to therapy (p = 0.006).


CONCLUSIONS
In our group of metastatic breast cancer patients, elevated HER-2/neu ECD levels are associated with decreased overall survival. With regard to progression-free survival, particularly patients with high HER-2/neu ECD levels seem to benefit from taxane-containing chemotherapy.
Müller
Volkmar
V
Department of Gynecology, University Hospital Hamburg-Eppendorf, Germany.
Witzel
Isabell
I
Lück
Hans Joachim
HJ
Köhler
Günter
G
von Minckwitz
Gunther
G
Möbus
Volker
V
Sattler
Daniel
D
Wilczak
Waldemar
W
Löning
Thomas
T
Jänicke
Fritz
F
Pantel
Klaus
K
Thomssen
Christoph
C
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D003520:Cyclophosphamide / Q000008:administration & dosage; D018450:Disease Progression; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000097:blood*
D014408:Biomarkers, Tumor; D003520:Cyclophosphamide; D015251:Epirubicin; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases