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- Posted Thursday May 14, 2015
Study of triple-negative breast cancer is most cited in AACR journal
TGen, Baylor, US Oncology study revealed therapeutic drug targets for aggressive form of breast cancer
PHOENIX, Ariz. - May 14, 2015 - At its Annual
Meeting, the American Association for Cancer Research (AACR)
announced that a scientific paper describing potential drug targets
following the unprecedented genomic sequencing of 14 metastatic
triple-negative breast cancer patients was the most cited study in
2013 of any published that year by AACR's journal Molecular
Cancer Therapeutics.
In the study, genomic sequencing - spelling out the billions of
pieces of genetic information in an individual patient's DNA -
revealed therapeutic drug targets for difficult-to-treat,
metastatic triple-negative breast cancer (TNBC).
The
Translational Genomics Research Institute (TGen), Baylor
University Medical Center and US Oncology Research investigators
found significant recurring mutations and other changes in more
than a dozen genes in patients treated at Baylor University Medical
Center at Dallas. In addition, the investigators identified
mutations previously unseen in metastatic TNBC and took the
sequencing data into account in selection of therapeutic protocols
specific to each patient's genetic profile.
"The nature of this disease cried out for innovative research
techniques such as whole genome sequencing coupled with new tools
for data analysis," said Dr. David Craig, Ph.D., TGen's Deputy
Director of Bioinformatics, one of the study'sco-lead
authors.
The mostfrequently mutated gene among the tumors was the
TP53 tumorsuppressor, and aberrations were observed in
additional tumor suppressor genesincluding CTNNA1, which was
detectedin two of six African American patients. Alterations
were also seen in the ERBB4 gene, known to be involved in
mammary-gland maturation during pregnancy and lactation, but not
previously linked to metastatic TNBC.
Each tumor was genomically unique, but the majority contained
alterations in one or both of the RAS/RAF/MEK/ERK and PI3K/AKT/MTOR
pathways.Targeted therapeuticintervention aimed at
these pathways achieved antitumor responses in
severalcases.
"The fact that this study has been cited more often than any other
in Molecular Cancer Therapeutics that year is a testament
to strong interest the oncology community has in understanding the
molecular basis of metastatic TNBC, and in the hypothesis that
targeting specific mutations in patients' TNBCs will improve
patients' outcomes," said Joyce O'Shaughnessy, M.D., the study's
other co-lead author. Dr. O'Shaughnessy is the Celebrating Women
Chair of Breast Cancer Research at Baylor University Medical Center
at Dallas, Chair of the US Oncology Network's Breast Cancer
Program, and a practicing oncologist with Texas Oncology.
Metastatic TNBC is a highly aggressive form of breast cancer that
does not express the estrogen receptor, progesterone receptor or
HER-2, the biomarkers successfully targeted in most breast
cancers.
Metastatic TNBC has a poor prognosis with a median survival rate
among metastatic patients of only one year. While
TNBCaccounts for only about 15 percent of all breast cancers,
its more aggressive biology makes it responsible for nearly one in
four deaths related to thisdisease.
"This study continues to stand as a great example of molecular
medicine in practice.The results have provided novel and
interesting clues into breast cancer biology and into the promise
and challenges of precision medicine," saidDr. John Carpten,
Ph.D., TGen's Deputy Director of Basic Science, Directorof
TGen's Integrated Cancer Genomics Division, and the study's senior
author.
The study, "Genome and transcriptome sequencing in prospective
triple negative breast cancer uncovers therapeutic
vulnerabilities,"was conducted by the Translational
Genomics Research Institute (TGen) and US Oncology Research with
support fromLife Technologies Corporation.
Molecular Cancer Therapeutics is one of several
peer-reviewedscientific journals published by the
35,000-member American Association for Cancer Research (AACR), the
oldest and largest scientific organization in the world focused on
every aspect of high-quality, innovative cancer research. The
programs and services of the AACR foster the exchange of knowledge
and new ideas among scientists dedicated to cancer research,
providetraining opportunities for the next generation of
cancer researchers, andincrease public understanding of
cancer.
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About TGen
Translational Genomics Research Institute (TGen) is a Phoenix,
Arizona-based non-profit organization dedicated to conducting
groundbreaking research with life changing results. TGen is focused
on helping patients with cancer, neurological disorders and
diabetes, through cutting edge translational research (the process
of rapidly moving research towards patient benefit). TGen
physicians and scientists work to unravel the genetic components of
both common and rare complex diseases in adults and children.
Working with collaborators in the scientific and medical
communities literally worldwide, TGen makes a substantial
contribution to help our patients through efficiency and
effectiveness of the translational process. For more information,
visit:www.tgen.org.
About Baylor University Medical Center at
Dallas
Baylor University Medical Center at Dallas, a 1025-bed
not-for-profit academic hospital, is a major patient care and
research center in the southwest. The nationally acclaimed medical
center serves as the North Texas flagship hospital for Baylor Scott
& White Health, the largest not-for-profit health care system
in Texas. In addition to its Level 1 trauma center, Baylor Dallas
is also home to many nationally ranked centers of excellence
including transplant, cardiovascular services, orthopedics,
digestive diseases, neurosciences, gynecology and oncology,
including Baylor Charles A. Sammons Cancer Center. In
2014,U.S. News & World Reportrecognized Baylor
Dallas 22nd consecutive year in its "America's Best Hospitals"
guide.
Physicians are members of the medical staff at one of Baylor Scott
& White Health's subsidiary, community or affiliated medical
centers and are neither employees nor agents of those medical
centers, Baylor University Medical Center at Dallas or Baylor Scott
& White Health.
About US Oncology Research
Supported by McKesson Specialty Health and The US Oncology
Network, US Oncology Research draws from a network of experienced
investigators and dedicated clinical staff who specialize in a
variety of oncology clinical trials, including Phase I-Phase IV as
well as observational trials. US Oncology Research serves nearly 70
research sites and approximately 240 locations managing about 225
active trials at any given time. Physicians in the research network
have enrolled more than 57,000 patients in nearly 1,300 trials
since inception in 1992 and have played a role in 48 FDA-approved
cancer therapies, nearly one-third of all cancer therapies approved
by the FDA to date. For more information call (800) 482-6700 or
visit www.usoncology.com/oncologists.
About Texas Oncology
Texas Oncology delivers high-quality cancer care with leading-edge
technology and advanced treatment and therapy options available to
help patients achieve "More breakthroughs. More victories."® in
their fights against cancer. Texas Oncology, a pioneer in
community-based cancer care, is an independent oncology practice
with sites of service throughout Texas and southeastern Oklahoma.
Texas Breast Specialists and Texas Urology Specialists, which focus
on all areas of breast and urologic care, are a part of Texas
Oncology.
Texas Oncology patients have the opportunity to take part in some
of the most promising clinical trials in the nation for a broad
range of cancers. Texas Oncology, through its affiliation with US
Oncology Research, has played a role in more than 50 FDA-approved
cancer-fighting drugs, nearly one-third of all cancer therapies
approved by the FDA to date.
Texas Oncology is united in healing with The US Oncology Network,
one of the nation's largest community-based cancer treatment and
research networks focused on advancing cancer care in America. As
an affiliate of The US Oncology Network, Texas Oncology is united
with more than 1,000 physicians and 10,000 cancer professionals
nationwide. The US Oncology Network is supported by McKesson
Specialty Health.
For more information, visit www.TexasOncology.com or call
1-888-864-I CAN (4226).
Press Contacts:
Steve Yozwiak
TGen Senior Science Writer
602-343-8704
[email protected]
Craig Civale
214-820-6251
[email protected]