Predicting tissue HER2 status using serum HER2 levels in patients with metastatic breast cancer.
BACKGROUND
Immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) are reliable ways to identify overexpression or amplification of the HER-2/neu (HER2, symbol ERBB2) gene, but each technique requires a high-quality tissue sample, which may not be available. We investigated whether serum concentrations of the HER2 extracellular domain (ECD) can be used as an alternative to tissue HER2 status in metastatic breast cancer, and we defined an optimal decision-level concentration of serum HER2 for prediction of tissue HER2 status.


METHODS
In 195 patients with metastatic breast cancer, we determined HER2 expression by IHC and performed FISH analysis on tumors for which IHC staining was graded as 2+. We measured serum HER2 by immunoassay and used ROC curve analysis to determine optimal serum HER2 ECD concentrations for differentiation between positive and negative HER2 status.


RESULTS
IHC results were 0/1+ for 30 (15%) of the patients, 2+ for 89 (46%), and 3+ for 76 (39%). FISH revealed HER2 amplification in 19 (21%) of the IHC 2+ tumors. Mean (SE) serum HER2 ECD was 22.2 (5.1) microg/L in the tissue HER2-negative group, significantly lower than the concentration of 363 (96) microg/L in the tissue HER2-positive group (P<0.0001). ROC curve analysis showed 95% specificity and 62% sensitivity for tissue HER2 positivity at 37 microg/L of serum HER2.


CONCLUSIONS
To use serum HER2 concentration as an alternative to direct determination of tissue HER2 status, we suggest 37 microg/L as a cutoff for predicting positive tissue HER2 with 95% specificity. Sensitivity, however, is low.
Kong
Sun-Young
SY
Research Institute & Hospital, National Cancer Center, Goyang-si, Gyeonggi-do, Korea.
Nam
Byung-Ho
BH
Lee
Keun Seok
KS
Kwon
Youngmee
Y
Lee
Eun Sook
ES
Seong
Moon-Woo
MW
Lee
Do Hoon
DH
Ro
Jungsil
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011237:Predictive Value of Tests; D012372:ROC Curve; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood / Q000378:metabolism*; D012189:Retrospective Studies
D018719:Erb-b2 Receptor Tyrosine Kinases