Serum EGFR and serum HER-2/neu are useful predictive and prognostic markers in metastatic breast cancer patients treated with metronomic chemotherapy.
BACKGROUND
Metronomic chemotherapy has been demonstrated to be of value in patients with advanced breast cancer. No reliable markers of response are available. In breast tumor, HER-2/neu is a prognostic factor, whereas no definite data exist for EGFR. The aim of the study was to evaluate the prognostic and predictive role of serum HER-2/neu and serum EGFR in breast cancer patients treated with low-dose chemotherapy.


METHODS
Serum levels of HER-2/neu (n = 135) and of EGFR (n = 113) were prospectively determined before the start of chemotherapy, after 2 months of treatment, and when progressive disease was diagnosed.


RESULTS
Elevated (>15 ng/mL) serum HER-2/neu before the start of chemotherapy was not associated with response rate, whereas elevated serum HER-2/neu at 2 months was significantly associated with reduced long-term clinical benefit (24 weeks) (P < .001), as well as changes in HER-2/neu levels between baseline and 2 months (P < .0001). Multivariate analysis identified a >or=20% increase of serum HER-2/neu as an independent factor for progression-free survival (PFS). Kinetics of serum HER-2/neu were significantly associated with PFS (P < .0001) and overall survival (OS) (P = .015). Low baseline serum levels of EGFR (<45 ng/mL) were predictive of reduced response rate both at 2 months (P = .031) and after 24 weeks (P = .022). Moreover, they were significantly associated with reduced PFS (P = .016) and OS (P = .015).


CONCLUSIONS
Serum HER-2/neu and EGFR may represent useful markers for early prediction of probability of response, PFS, and OS in patients with advanced breast cancer treated with metronomic chemotherapy.
Sandri
Maria Teresa
MT
Unit of Laboratory Medicine, European Institute of Oncology, Milan, Italy. maria.sandri@ieo.it
Johansson
Harriet Ann
HA
Zorzino
Laura
L
Salvatici
Michela
M
Passerini
Rita
R
Maisonneuve
Patrick
P
Rocca
Andrea
A
Peruzzotti
Giulia
G
Colleoni
Marco
M
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage; D018450:Disease Progression; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D066246:ErbB Receptors / Q000097:blood*; D005260:Female; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood*; D013792:Thalidomide / Q000008:administration & dosage
D014408:Biomarkers, Tumor; D003520:Cyclophosphamide; D066246:ErbB Receptors; D008727:Methotrexate; D018719:Erb-b2 Receptor Tyrosine Kinases; D013792:Thalidomide