The results of the next-generation sequencing analysis of the BOLERO-2 samples showed that specific activating PIK3CA mutations are not in themselves predictive of clinical benefit from mTOR inhibitors, possibly because there are other ways to activate mTOR independently of PI3K.
“It is probably more likely to predict response to specific PI3K inhibitors,” suggested the paper’s discussant, Stephen R.D. Johnston, MA, MD, PhD, Professor of Breast Cancer Medicine at The Royal Marsden Hospital in the United Kingdom.
It appears that the more “normal” the estrogen receptor–positive cancer cell (ie, the fewer the mutations), the better the benefit from mTOR inhibitors, he noted.
“Therefore we still should select for treatment on the basis of clinical criteria suggesting acquired resistance to previous nonsteroidal aromatase inhibitors. Perhaps future patients with multiple genetic alterations could avoid treatment and its associated toxicity,” Dr. Johnston suggested. ■
Disclosure: Dr. Johnston reported no potential conflicts of interest.
The search for a biomarker of benefit from mTOR inhibitors in breast cancer fell flat in an exploratory genetic analysis of the BOLERO-2 trial, presented at the 2013 ASCO Annual Meeting by Gabriel N. Hortobagyi, MD, FACP, Professor of Breast Medical Oncology at The University of Texas MD Anderson...