Changes over time of extracellular domain of HER2 (ECD/HER2) serum levels have prognostic value in metastatic breast cancer.
BACKGROUND
Blood levels of the extracellular domain of HER-2/neu (ECD/HER2) have been suggested to have potential as a tumor marker in breast cancer. Our aim was to assess the prognostic value of baseline levels of ECD/HER2, but more importantly changes in levels over time, in women with metastatic breast cancer.


METHODS
Baseline and serial levels of ECD/HER2 were measured in 158 women with newly-diagnosed metastatic breast cancer, in whom we previously performed serial measurement of plasma osteopontin. ECD/HER2 was measured in 1,282 serum samples using a validated ELISA at baseline and every 3-12 weeks during and after therapy until death (median, n=8 samples per patient). Multivariate time-dependent survival analyses were conducted using models that right-censored patient outcomes 3, 6 and 12 months after last known ECD/HER2 measurement.


RESULTS
Thirty-four patients (22%) had elevated baseline ECD/HER2 (median 10.2 ng/ml: range 4.1-40.4 ng/ml). In univariate analysis, elevated baseline ECD/HER2 was associated with short survival (P=0.001). In a multivariate model incorporating standard clinical prognostic factors, baseline ECD/HER2 was significantly associated with survival duration (RR 1.029; P=0.020). Presence of visceral metastases and ECOG status 2-4 also retained significance. In a multivariate model incorporating standard prognostic factors and changes in sequential ECD/HER2 levels, an ECD/HER2 increase of >12 ng/ml at any time was the variable with most prognostic value for poor survival (RR 6.10; P=0.0003); poor ECOG status also retained significance.


CONCLUSIONS
Increases over time of ECD/HER2 levels were strongly associated with poor survival in this cohort of women with metastatic breast cancer.
Bramwell
Vivien H C
VH
London Regional Cancer Program, London, ON, Canada. vivienbr@cancerboard.ab.ca
Doig
Gordon S
GS
Tuck
Alan B
AB
Wilson
Sylvia M
SM
Tonkin
Katia S
KS
Tomiak
Anna
A
Perera
Francisco
F
Vandenberg
Theodore A
TA
Chambers
Ann F
AF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood* / Q000737:chemistry; D001943:Breast Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000401:mortality*; D005260:Female; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D011379:Prognosis; D011446:Prospective Studies; D017434:Protein Structure, Tertiary; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood* / Q000737:chemistry; D013997:Time Factors; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases