Circulating HER2 DNA after trastuzumab treatment predicts survival and response in breast cancer.
BACKGROUND
Only a subset of breast cancer patients responds to the HER2 inhibitor trastuzumab, and methods to identify responders are needed.


METHODS
We studied 28 patients with metastatic breast cancer that had amplified human epidermal growth factor receptor 2 (HER2) genes in their primary tumour and were treated with a combination of trastuzumab and chemotherapy. Plasma was collected and amplification of the HER2 gene in circulating DNA and the amounts of the extracellular domain (ECD) of HER2 were measured just before first treatment (n=28) and just before second treatment three weeks later (HER2 DNA (n=22), HER2 ECD (n=23)).


RESULTS
Pre-treatment levels of HER2 gene amplification and HER2 ECD did not correlate to clinical parameters. However, 9 out of 22 patients had a more than a 14% (2 x SD) reduction in HER2 gene amplification following treatment and showed improved response (p=0.02), and overall survival (p=0.05). HER2 ECD kinetics did not correlate to clinical data.


CONCLUSIONS
We suggest that a decrease in HER2 gene amplification in the plasma predicts a more favourable response to trastuzumab.
Sorensen
Boe S
BS
Department of Clinical Biochemistry, Aarhus University Hospital, Norrebrogade 44, DK 8000 Aarhus C, Denmark. boesoere@rm.dk
Mortensen
Lise S
LS
Andersen
Jørn
J
Nexo
Ebba
E
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004247:DNA / Q000097:blood*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017434:Protein Structure, Tertiary; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics*; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D004247:DNA; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human