Serum levels of HER2 ECD can determine the response rate to low dose oral cyclophosphamide and methotrexate in patients with advanced stage breast carcinoma.
BACKGROUND
The proto-oncogene HER2/neu encodes for a transmembrane receptor protein whose overexpression in breast cancer may be associated with poor prognosis. Its extracellular domain (HER2 ECD) can be shed into the circulation. The purpose of this study was to evaluate the predictive value of HER2 ECD in patients with advanced breast cancer.


METHODS
HER2 ECD was determined in 39 patients with advanced breast cancer, treated with oral cyclophosphamide and methotrexate (CM) at low doses. HER2 ECD levels were determined with the Bayer Immuno 1 HER2/neu assay before and after 2 months of chemotherapy, when all the patients were re-evaluated.


RESULTS
Based on the response to chemotherapy, the patients were divided into two groups: progressive disease (PD, 14 patients) and patients with clinical benefit (CB; i.e. patients with stable or responsive disease, 25 patients). The patients with PD had a mean baseline value of HER2 ECD of 38.3+/-69.2 ng/ml, while the group of CB showed lower levels (9.2+/-2.3 ng/ml, p<0.05). After 2 months, the mean value of HER2 ECD in the PD group increased to 71.6+/-146 ng/ml, while in the other group the levels did not change (9.7+/-2.4 ng/ml). At follow-up, significant differences were noted in both the time to progression and overall survival, with patients with increased levels of HER2 ECD at baseline (> or = 15 ng/ml) showing a worse clinical outcome.


CONCLUSIONS
Increased pretreatment levels of HER2 ECD identify a subset of patients with more aggressive tumors and less response to CM chemotherapy. During therapy, increasing levels of HER2 ECD are associated with disease progression.
Sandri
Maria Teresa
MT
Division of Pathology and Laboratory Medicine, European Institute of Oncology, Milan, Italy. maria.sandri@ieo.it
Johansson
Harriet
H
Colleoni
Marco
M
Zorzino
Laura
L
Passerini
Rita
R
Orlando
Laura
L
Viale
Giuseppe
G
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009367:Neoplasm Staging; D017434:Protein Structure, Tertiary; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood*
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D003520:Cyclophosphamide; D008727:Methotrexate; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases; C000715470:MAS1 protein, human