Initial
results from an ongoing clinical trial, the first designed to examine
the utility of whole-genome sequencing for triple negative breast
cancer, were reported this during the CRTC-AACR San Antonio Breast
Cancer Symposium.
The
results indicate activation of targets not previously associated with
triple negative disease and could point toward new treatment strategies.
Based on mutations uncovered by sequencing, physicians recommended the
women enter treatment protocols for either existing drugs or new agents
being evaluated in pharma-sponsored clinical trials.
Triple
negative breast tumors, which make up nearly 20% of breast cancers, do
not respond to treatment with targeted therapies such as Herceptin
(trastuzumab).
Of
eleven tumors sequenced to date, each was genomically unique, but
commonalities were observed. Some patients displayed amplified genes in
the RAS pathway; one patient had amplification of the BRAF oncogene, as
well as activation of a growth pathway known as the MEK/AKT pathway. This patient displayed an impressive response to a MEK/AKT inhibitor
currently in a phase I clinical study.
“Those
results are quite striking considering that these are women with
advanced disease,” said Joyce O’Shaughnessy, MD, who presented the
data. “If MEK/AKT activation is found to be present in a substantial
fraction of triple negative patients, inhibitors of this pathway could
prove a significant tool in fighting this disease.”
O’Shaughnessy is medical director and co-chair of the Breast Cancer
Research Committee, US Oncology Research; a practicing oncologist with
Texas Oncology; and the Celebrating Women Chair of Breast Cancer
Research at Baylor Charles A. Sammons Cancer Center.
“This
is among the largest studies of a single tumor type in which whole
genome sequencing is being used to identify potential options for
targeted treatment,” said John Carpten, PhD, director of the
Integrated Cancer Genomics Division at the Translational Genomics
Research Institute (TGen). “As the field of genomic medicine matures,
this study is sure to provide key early insights into how sequencing can
best be utilized in the clinic.”
The
study, titled “Next Generation Sequencing Reveals Co-Activating Events
in the MAPK and PI3K/AKT Pathways in Metastatic Triple Negative Breast
Cancers,” is sponsored by the Translational Genomics Research Institute
(TGen) and US Oncology Research with support from Life Technologies
Corporation. Whole-genome sequencing of tumors and normal tissue was
performed on Life Technologies’ Applied Biosystems SOLiD platform, and
results were validated in a CLIA-certified laboratory.
