Predictive relevance of soluble CD44v6 serum levels for the responsiveness to second line hormone- or chemotherapy in patients with metastatic breast cancer.
Concentrations of soluble CD44 standard (sCD44std) and CD44 variant 6 (sCD44v6) isoforms were determined in the sera of 59 patients with distant metastasis from breast cancer receiving second line hormone- or chemotherapy, in comparison to 46 breast cancer patients without detectable recurrent disease and 21 healthy blood donors. The sera of non-metastatic breast cancer, patients contained sCD44std and sCD44v6 concentrations similiar to those of healthy blood donors. In sera of patients with distant metastasis from recurrent breast cancer the median values of sCD44std and sCD44v6 were significantly higher (sCD44std: 502 ng/ml, p=0.03; sCD44v6: 193 ng/ml, p = 0.002) in comparison to healthy blood donors and patients with non-metastatic disease (p<0.001 for both parameters). A significant correlation was observed between sCD44v6 serum concentrations and the number of metastasized organs (p=0.0018), serum LDH concentrations (p<0.0001), tumor grading (p=0.025) and the presence of hepatic metastasis (p=0.028). Furthermore, sCD44v6 expression was associated with the patient's responsiveness to second line hormone- or chemotherapy. Non-responders had significantly higher sCD44v6 levels compared with the responder group (median: 447 ng/ml vs 171 ng/ml; p=0.0007). Logistic regression analysis indicated that sCD44v6 serum levels above 250 ng/ml (p =0.033) and the presence of hepatic metastasis (p=0.009) were independent factors predicting an unfavourable response to therapy.
Kopp
R
R
GSF-National Research Center for Environment and Health, Munich, Germany.
Classen
S
S
Wolf
H
H
Gholam
P
P
Possinger
K
K
Wilmanns
W
W
D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D000951:Antigens, Neoplasm / Q000097:blood*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D018960:Hyaluronan Receptors / Q000097:blood*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008113:Liver Neoplasms / Q000097:blood / Q000556:secondary; D016015:Logistic Models; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000175:diagnosis*; D009363:Neoplasm Proteins / Q000097:blood; D009928:Organ Specificity; D011237:Predictive Value of Tests; D012074:Remission Induction; D012307:Risk Factors; D012995:Solubility; D016896:Treatment Outcome
D000951:Antigens, Neoplasm; D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; C112697:CD44v6 antigen; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D009363:Neoplasm Proteins; D004317:Doxorubicin; D003520:Cyclophosphamide; D007770:L-Lactate Dehydrogenase; D000469:Alkaline Phosphatase; D005472:Fluorouracil; D008727:Methotrexate