Biomedical Engineering Reference
In-Depth Information
found a correlation between high expression and worse outcome.
Thus, the direct measurement of gene amplification appears to be
a more reliable approach. Overall, in studies where it was reported,
the mean relative risk for HER-2 amplification was 2.74 for overall
survival and 2.04 for disease free survival [66]. A recent molecular
analysis of gene expression by cDNA microarray has identified
HER-2 amplified breast cancer based on mRNA expression and
found a similar poor prognosis for this patient subgroup [67]. Thus,
the association of HER-2 amplification and poor prognosis in breast
cancer has been a consistent finding over many studies using DNA,
RNA and protein based approaches.
Figure 4.3
HER-2 as a prognostic marker. Survival of node negative early-
stage breast cancer patients stratified for HER-2 amplification.
Reproduced with permission from Press
et al.
[197].
4.5
HER-2 Amplification as a Predictive
Biomarker for Response to HER-2 Targeted
Agents in Breast Cancer
4.5.1
Trastuzumab
A predictive biomarker is one that predicts the likelihood of
response to a specific agent [68]. The preclinical data described
above demonstrating the transforming potential of HER-2 and the
prognostic significance of the amplification or overexpression of
HER-2 suggest that it would be a predictive biomarker for the use
