Thursday, December 8, 2011

More TNBC treatment tools on the horizon? Whole-genome sequencing

PHOENIX, Ariz. -- 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 today 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 percent 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, M.D., 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."

Dr. 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, Ph.D., 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.

About Baylor Health Care System

Baylor Health Care System is a not-for-profit, faith-based supporting organization providing services to a network of acute care hospitals and related health care entities that provide patient care, medical education, research and community service. Baylor recorded more than 2.6 million patient encounters, $3.8 billion in total operating revenue, $4.4 billion in total assets and $513.5 million in community benefit in fiscal year 2010. Baylor's network of more than 300 access points includes 27 owned/operated/ ventured/affiliated hospitals, 23 joint ventured ambulatory surgical centers, 50 satellite outpatient locations, four senior centers and 156 HealthTexas Provider Network physician clinics.

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 participates in innovative clinical trials from Phase I through Phase IV through US Oncology Research, which has helped to develop 43 FDA approved cancer therapies.

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 http://www.TexasOncology.com or call 1-888-864-I-CAN (4226).

About TGen

The Translational Genomics Research Institute (TGen) is a Phoenix, Arizona-based non-profit organization dedicated to conducting groundbreaking research for life changing results. Research at TGen is focused on helping patients with diseases such as cancer, neurological disorders and diabetes. TGen is on the cutting edge of translational research where investigators are able to unravel the genetic components of common and complex diseases. Working with collaborators in the scientific and medical communities, TGen believes it can make a substantial contribution to the efficiency and effectiveness of the translational process. TGen is affiliated with the Van Andel Research Institute in Grand Rapids, Michigan. For more information, visit: http://www.tgen.org.

About US Oncology Research

McKesson Specialty Health conducts clinical trials through US Oncology Research, which draws from a network of experienced investigators and dedicated clinical staff who specialize in Phase I through Phase IV oncology clinical trials. US Oncology Research serves more than 90 sites in over 250 locations managing more than 200 active trials at any given time. Physicians in the research network have enrolled more than 50,000 patients in over 1,200 trials since inception in 1992 and have contributed to the development of 43 cancer therapies approved by the FDA. For more information call 800-482-6700, option 4 or visit http://www.usoncology.com/oncologists.

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