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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]


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