60 AACR Cancer Progress Report 2013
targeted therapy trastuzumab was originally developed to treat
patients with breast cancers that overexpress the HER2 protein
due to the presence of extra copies of the HER2 gene and later
shown to prolong survival for patients with stomach cancer
harboring extra copies of the HER2 gene (167).
Currently, however, our use of large-scale genomic data
is limited to the research setting. Here, it is guiding the
development of new cancer drugs, directing the repurposing of
established molecularly targeted therapies, and aiding clinical
researchers in assigning patients, like Carol Weinbrom, to the
most appropriate therapies and clinical trials.
Recently, two independent large-scale genomic studies
provided insight that could benefit some patients with breast
cancer that tests negative for HER2 gene amplification (168,
169). These patients are considered ineligible for treatment
with HER2-targeted therapies like trastuzumab. However, the
large-scale genomic analyses found that some tumors that test
negative for HER2 gene amplification harbor a mutation in the
HER2 gene that causes their HER2 proteins to be overactive in
the same way that HER2 gene amplification does, suggesting
that they might be sensitive to HER2-targeted therapies.
Thus, a clinical trial has been launched to evaluate whether
the investigational HER2-targeted therapy neratinib is a good
treatment option for patients with metastatic breast cancer
harboring HER2 gene mutations but not amplifications.