Comparison of HER-2 status between primary breast cancer and corresponding distant metastatic sites.
BACKGROUND
The humanized anti-HER-2 monoclonal antibody trastuzumab (Herceptin) is a new treatment modality for metastatic breast cancer, the efficacy of which is directly correlated with the HER-2 status of the tumour, evaluated either by immunohistochemistry (IHC) and/or by fluorescence in situ hybridisation (FISH). This analysis is generally performed on the primary tumour. There are few data regarding the HER-2 status in the corresponding distant metastases.


METHODS
HER-2 status in 107 patients with a primary breast tumour and at least one distant metastatic lesion was analysed by IHC and FISH.


RESULTS
We found similar levels of amplification (25% and 24%) and overexpression (13% and 19%) of HER-2 in primary and metastatic samples, respectively. Among paired primary/metastatic tumours, six (6%) showed discordance by HercepTest(TM) (n = 100): all six cases showed greater Her-2 overexpression in the metastatic tissue. By FISH (n = 68), five (7%) cases were discordant: two cases were amplified in the primary tumour but not in the metastasis, and three samples showed amplification in the metastasis but not in the primary. Finally, we analysed HER-2 status in different metastatic lesions from 17 patients that had at least two distant metastatic sites. Discordance between different sites from the same patient was 18% by IHC and 19% by FISH.


CONCLUSIONS
Between the paired primary tumour and distant metastatic lesions, 94% and 93% of samples had concordant HER-2 status when analysed by IHC or FISH, respectively. These results do not support routine determination of HER-2 on metastatic sites, particularly when FISH results from the primary tumour are available.
Gancberg
D
D
Translational Research Unit and Data Centre, Jules Bordet Institute, Brussels, Belgium.
Di Leo
A
A
Cardoso
F
F
Rouas
G
G
Pedrocchi
M
M
Paesmans
M
M
Verhest
A
A
Bernard-Marty
C
C
Piccart
M J
MJ
Larsimont
D
D
D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D001943:Breast Neoplasms / Q000473:pathology*; D015331:Cohort Studies; D016001:Confidence Intervals; D046508:Culture Techniques; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D009362:Neoplasm Metastasis / Q000473:pathology*; D009367:Neoplasm Staging; D009378:Neoplasms, Multiple Primary / Q000473:pathology*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D012494:Sampling Studies; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases