Abstract
In the SAFIR01 trial, whole-genome analysis was performed in samples from 248 patients with metastatic breast cancer, and genomic alterations targetable by cancer drugs were found in 172 of the tumors.
Breast cancer was one of the first cancers for which oncologists were able to tailor treatments to a tumor's molecular characteristics. However, this form of personalized medicine typically depends on only a few measures, such as overexpression of HER2 or the presence of receptors for estrogen and progesterone.
Now Fabrice André, MD, PhD, of the Institute Gustave-Roussy in Villejuif, France, and colleagues have taken a broader look, analyzing biopsies from more than 400 patients with metastatic breast cancer in what they reported as the first large-scale trial of whole-genome cancer testing.
In the SAFIR01 trial, the team used array-comparative genomic hybridization to identify duplications or deletions throughout the genome and sequenced 2 genes—PI3 kinase and AKT1—that are often mutated in a variety of cancers.
André and his colleagues found that 172 of the 248 patients for whom they obtained results carried genomic changes targeted by drugs that are currently under development. One example of these alterations is an amplification of the MDM2 gene; 2 phase I trials of an MDM2 inhibitor are under way for patients with leukemia, lymphoma, or solid tumors.
Standard clinical techniques, such as testing for HER2 overexpression, would not have distinguished these individuals, André points out. As a result, 26 patients were able to receive targeted therapy through clinical trials. However, the team also found that about 20% of the subjects showed rare genomic alterations that aren't on the drug development agenda.
“We can do a whole-genome approach on a large number of patients in the context of daily practice,” says André, whose team presented its findings on October 1 at the ESMO 2012 Congress of the European Society for Medical Oncology in Vienna, Austria.
André says that the team plans to expand the analysis by sequencing 100 genes that are frequently mutated in breast cancer, using data compiled by the International Cancer Genome Consortium.
The researchers show that “it's possible to take biopsies from metastatic lesions, analyze them using genomic technologies, and apply that method on a large scale,” says Sherene Loi, MD, PhD, of the Jules Bordet Institute in Brussels, Belgium, who is not connected with the study. However, she adds that the unanswered question is whether and when the approach will help patients live longer.
