HER-2 amplification level linked to trastuzumab response in breast cancer
MedWire News: A high level of human epidermal growth factor receptor 2 (HER-2) gene amplification is associated with a greater likelihood of achieving pathologic complete response (pCR) in non-metastatic breast cancer patients treated with trastuzumab-based neoadjuvant therapy, French researchers report.
In contrast, the level of amplification does not significantly influence the length of recurrence-free (RFS) or overall survival (OS), say Séverine Guiu (Georges-Francois Leclerc Cancer Center, Dijon) and colleagues.
The researchers carried out the study to determine whether the HER-2 gene amplification level, assessed using fluorescence in situ hybridization (FISH) assays, influenced the outcome of treatment with trastuzumab-based neoadjuvant therapy.
They classified tumors from 99 patients with non-metastatic breast cancer into those with low HER-2 amplification (LA; 6-10 signals per nuclei) and those with high amplification (HA; >10 signals).
In all, 33 tumor samples had LA and 66 had HA. Tumor stage, nodal status, hormone receptor status, and treatment given did not differ between the two groups, but the HA tumors had a higher histological grade than the LA tumors.
A significantly higher proportion of patients with HA tumors achieved pCR compared with patients with LA tumors, at 55% versus 24%. In multivariate analysis, the level of amplification was significantly independently associated with pCR, the team notes.
After a median follow-up period of 46 months there was no significant difference between RFS or OS rates for patients with either HA tumors or LA tumors.
However, the researchers observed that RFS time tended to be shorter in the HER-2 HA group compared with the LA group, suggesting that "a high level of HER-2 amplification could be a poor prognostic factor even though it was associated with a good initial sensitivity to trastuzumab," they say.
"In light of these results, the level of HER-2 amplification could be a useful tool to decide whether to administer neoadjuvant therapy and could therefore also increase the rate of conservative surgery," the team concludes in the British Journal of Cancer.
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By Laura Dean