HER2 gene amplification could broaden trastuzumab suitability
MedWire News: Assessment of human epidermal growth factor receptor (HER2) gene amplification, rather than HER2 positivity, in patients with unresectable or metastatic gastric cancer (GC) may be a more sensitive method for selecting patients for trastuzumab therapy, researchers suggest.
Their assertion is based on the discovery that 10.1% of their sample of 148 patients with advanced GC tested positive for HER2 by immunohistochemistry (IHC), whereas 18.2% tested positive by fluorescence in situ hybridization (FISH), and 21.6% by dual-colour silver-enhanced in situ hybridization (dc-SISH).
The study also shed new light on the significance of HER2 positivity for GC survival.
"HER2 gene amplification approaches might be an optimal HER2/neu testing strategy for the selection of HER2-positive GC patients who are candidates to be treated with anti-HER2 therapies," write Carlos Gómez-Martin (Spanish National Cancer Research Centre, Madrid) and team in the Journal of Clinical Pathology.
The study participants were aged an average of 67 years; 73% were male, and 51% had intestinal histology GC.
Both methods showed that HER2 amplification was significantly more common in patients with GC of intestinal histology than in those with other types of GC tumors.
With FISH analysis, HER2 positivity was detected in 23% of intestinal histologic gastric tumors compared with 4% of nonintestinal gastric tumors, while dc-SISH analysis gave rates of 26% and 6%, respectively.
Regardless of the testing technique used, HER2 positivity correlated significantly with greater overall survival. With IHC, median overall survival was more than twice as long among HER2-positive patients than patients without HER2 overexpression (21.4 vs 9.8 months), and a similar difference was seen for FISH (19.6 vs 9.7 months) and dc-SISH (19.6 vs 9.7 months) analysis.
Gómez-Martin et al say their findings "corroborate phase III [Trastuzumbab for Gastric Cancer] study results" indicating that patients with HER2 overexpression or amplification who are given standard chemotherapy show longer survival than those without overexpression.
They suggest the survival advantage associated with addition of trastuzumab to chemotherapy in HER2-metastatic GC may be therefore be conferred by the HER2 protein or HER2 amplification.
By Cher Thornhill