Yale: Searching for more individual genes to predict responses to breast
cancer therapy may not work, a new study suggests. Instead, scientists
and clinicians need to pay attention to abnormalities in networks of
genes, Yale researchers report in a paper published Oct. 10 in the
journal Annals of Oncology.
The Yale team studied all the genes of
200 patients who had HER2-positive breast cancer (about 15% of breast
cancers have too many copies of the HER2 gene). About half of the
patients responded very well to HER2-targeted therapy, but half did not,
researchers reported. However, they were not able to find a single
gene abnormality that could serve as a biomarker to predict treatment
outcomes for all patients.
“If we keep looking for one marker at a
time, we will not find a clinically useful marker to guide treatment
selection for these drugs,” said Dr. Lajos Pusztai, researcher at the
Yale Cancer Center and senior author of the study.
However, they
did find abnormalities in several dozens of genes in a single molecular
network that aid in transmitting chemical information from the HER2
molecule on the cell surface to the interior of the cell. The presence
of these abnormalities predicted which patients would be resistant to
standard therapies. Only few patients, however, shared the same
individual abnormalities, and the network was affected at different
genetic locations in different patients.
“You can look at these
treatment-resistant cancers like a broken car — there are many
different ways for a car to break down but the outcome is the same: The
car is not working,” Pusztai said.
He said a diagnostic test that
can pinpoint abnormalities in this network of genes might help customize
treatment. A new generation of drugs to treat women with HER2-positive
breast cancer are now available and are effective, but are also
extremely costly, Pusztai said. “We could save this new generation of
drugs for those who really need it and treat women who don’t with
therapies that are less intense.”