Herbert Irving Comprehensive Cancer Center

Dear Cancer Center members,

The personnel of the Genomics Share Resource Facility will undergo a hands on training in a new platform of genomic analysis from Sept 5th to Sept 12th.
This training is essential for incorporating a new ultra-high throughput sequencing system in the facility and provide you with this crucial new service.
During this time we will not be able to process array samples, however access to the ancillary equipment in the 4th floor of the ICRC (Typhoon, Q-PCRs…) will not be interrupted.
All services will be restored on Monday Sept 15th.  

We remain committed to provide all Cancer Center members a readily available service and rapid turnaround in the processing of their samples.

Sincerely,
Adolfo Ferrando

The 2008 Herbert Irving Comprehensive Cancer Center Annual Retreat will be held on Monday, October 6th at the Wave Hill Public Garden and Cultural Center Bronx, NY.

The purpose of this retreat is to bring together the cancer center community at Columbia Medical Center to discuss recent advances in research and foster scientific communication and collaboration.

Please note that the Annual Retreat is limited to members of the Herbert Irving Comprehensive Cancer Center. There is limited space, but we will do our best to accommodate all requests Attendance will be granted on a first come, first serve basis.

Bus transportation from HICCC to the retreat will be provided. Information about departure time and location will be emailed to everyone taking the bus to Wave Hill. 

To attend the retreat, please fill out the online Retreat Registration Form by September 15th, registration will not be accepted or changed after that date.

If you have any questions or need any further information, please contact Ralph Maldari at 212-851-4748.

Ever since Carlos Cordon-Cardo peered at tumor cells under a microscope as a medical student in Spain, he has wanted to improve cancer diagnosis. His concern then, and now, is that cancer tissue samples from two different patients might appear the same, but one person after treatment will experience a recurrence and may die, while the other individual may live because the disease does not come back. There is no way a doctor can predict which course the disease will take.

To understand what causes variation in cancers as a means to provide better diagnoses, prognoses, and treatment for patients has been Dr. Cordon-Cardo’s professional quest for the past 30 years as a research pathologist and cancer biologist. Recently, Dr. Cordon-Cardo, who brought his quest to Columbia University in 2006, has moved a step closer to fulfilling his decades-long aspiration.

Carlos Cordon-Cardo, M.D., Ph.D., and colleagues have developed a new platform, called systems pathology, which relies on microscopy, optical engineering, clinical parameters, biomarkers and advances from the human genome project, and computer algorithms that analyze the data, to create an objective and quantitative measure of tissue structures and molecular components in tumor cells to help predict prostate cancer behavior.

In an application of the tool, published in the Journal of Clinical Investigation in 2007, the method could predict recurrence with high accuracy for each of almost 400 men with prostate cancer who had been treated with surgical removal of their prostates.

Read the full article in the Spring/Summer edition of P&S.

The National Cancer Institute is pleased to announce the first of a series of service programs in its cancer Biomedical Informatics Grid (caBIG™) Enterprise Support Network (ESN), designed to support and extend caBIG™ tools and infrastructure.  The caBIG™ initiative, overseen by the NCI Center for Biomedical Informatics and Information Technology, was conceived to advance basic and clinical research on cancer and improve clinical outcomes for patients. The initiative has successfully launched key tools, infrastructure and policy resources that enable individuals and organizations in the cancer community and other domains to be more efficient and innovative.  As caBIG™ moves into the next phase of development and expanded deployment, the caBIG™ Enterprise Support Network will help 21st century biomedical researchers integrate caBIG™ technology at their institutions. The ESN represents a major step forward, by authorizing a variety of external organizations, both academic and commercial, to deliver knowledge management and support services in their particular areas of expertise.    

The ESN will provide support for caBIG™ standards, applications, and infrastructure to individuals, including end users, administrators and IT staff;  organizations and institutions of the current caBIG™ community; the broader cancer research enterprise, and eventually others in the biomedical community who can benefit from improved interoperability.  The first programs awarded are five domain-specific caBIG™ Knowledge Centers.

Knowledge Centers are NCI-supported entities, each forming the nucleus of an expanding research and clinical community around the specific domains in which they have expertise. As an authoritative repository of knowledge and information about caBIG™ tools and technologies, the caBIG™ Knowledge Center provides the resources, expertise and support to drive broader implementation of caBIG™ tools and technologies across that domain.

The caBIG™ Knowledge Centers awarded are:

• caGrid –The Ohio State University and The Ohio State Comprehensive Cancer Center, with the University of Chicago and the Argonne National Lab
• Clinical Trials Management Systems – Duke University Comprehensive Cancer Center, with Robert H. Lurie Comprehensive Cancer Center at Northwestern University, Cancer and Leukemia Group B – Information Systems (GALGB-IS), and SemanticBits
• Molecular Analysis Tools – Columbia University Herbert  Irving Comprehensive Cancer Center with The Broad Institute of MIT and Harvard
• Tissue/Biospecimen Banking and Technology Tools – Siteman Cancer Center, Washington University at St. Louis
• Vocabulary – Mayo Clinic with SemanticBits

caBIG™ Knowledge Centers will offer:

• Domain expertise, technical and end-user documentation
• Comprehensive and up-to-date installation packages for caBIG™ tools
• Administering open source development of caBIG™ tools by the community
• Collection and monitoring of defect reports, feature requests, and end-user requirements
• Development of caBIG™ training

The resources of each caBIG™ Knowledge Center will be available through Web-based technologies, including a searchable caBIG™ Knowledge Base related to the specific technologies in their respective domains and the implementation of those technologies to solve real-world biomedical research problems.

Details about the individual caBIG™ Knowledge Centers that have been awarded are given below.

caGrid – The Ohio State University and The Ohio State Comprehensive Cancer Center, with The University of Chicago and the Argonne National Lab

caGrid is the underlying software infrastructure that provides the basis for connectivity among cancer institutions around the country. It enables research groups to tap into the emerging collection of detailed cancer research data while supporting their individual investigations.  With caGrid, institutions use their locally managed access control policies to manage and securely share information and analytic resources on the Grid.  The Ohio State University is the lead developer for the caGrid core infrastructure. Additionally, OSU has extensive experience developing domain-specific extensions and applications using caGrid.  The University of Chicago and Argonne National Lab develop the Globus Toolkit used in caGrid. These organizations have extensive experience with Grid computing and lead the development of caGrid workflow infrastructure. This Knowledge Center will help individuals and groups who: a) need a solution to share applications and data on the grid, b) use caGrid as part of their existing software solutions, c) extend caGrid-enabled applications, or d) contribute new features and fixes to caGrid.

Clinical Trials Management Systems – Duke University Comprehensive Cancer Center, with Northwestern University, Cancer and Leukemia Group B – Information Systems (GALGB-IS), and SemanticBits

caBIG™ provides a robust collection of interoperable software tools that support the conduct of clinical trials. They include software for managing study participant registration information (the Cancer Central Clinical Participant Registry, or C3PR), an application for the scheduling and tracking of patient activities during the course of a study (the Patient Study Calendar, or PSC), a system for tracking and managing adverse events (cancer Adverse Events Reporting System, or caAERS), and a system for translating and routing clinical data (cancer Data Exchange, or caXchange), among others. The Duke team includes key partners who have contributed widely to the development and implementation of caBIG™ clinical trials management systems tools.  This Knowledge Center will help organizations that want to adopt or adapt these tools to strengthen and streamline their clinical research activities.

Molecular Analysis Tools – Columbia University Herbert  Irving Comprehensive Cancer Center with The Broad Institute of MIT and Harvard

The molecular analysis tools of caBIG™ facilitate the discovery of the next generation of cancer diagnostics and therapeutics to realize the vision of Molecular, or Personalized Medicine.  Four key tools will be supported by this Knowledge Center: geWorkbench, which provides an innovative, open-source software platform for genomic data integration, bringing together analysis and visualization tools for gene expression, sequences, pathways, and other biomedical data; GenePattern, which puts sophisticated computational methods into the hands of the biomedical research community; caArray, a system that supports the management and exchange of array data and annotations; and caIntegrator, a novel translational informatics platform that allows researchers and bioinformaticians to access and analyze clinical and experimental data across multiple clinical trials and studies. Columbia and The Broad Institute developed the first two tools and have helped facilitate their wide use; moreover, both Columbia and The Broad have integrated these systems with caArray. Columbia has first hand knowledge of how caIntegrator can be adopted to support research needs, acquired through a recently completed adoption activity at the Herbert Irving Cancer Center.  This Knowledge Center will help organizations integrate these life sciences tools into their research workflows.

Tissue/Biospecimen Banking and Technology Tools – Siteman Cancer Center, Washington University at St. Louis

caTissue is caBIG's tissue bank repository tool for biospecimen inventory, tracking, and basic annotation. This tool permits users to track the collection, storage, quality assurance, and distribution of specimens as well as the derivation and aliquotting of new specimens from existing ones (e.g. for DNA analysis). It also allows users to find and request specimens that may then be used in correlative molecular studies. The Washington University team developed and supports the caTissue application (caTissue Core and now caTissue Suite) and utilizes these tools in the management of their own large biospecimen repository.  The Knowledge Center will provide biospecimen repository domain experts, biomedical informaticians, software engineers, technical support specialists, and training experts to support individuals and organizations that want to implement this biospecimen technology.

Vocabulary – Mayo Clinic, with SemanticBits

The ability of caBIG™ tools to share and integrate information from disparate sources is dependent on the use of robust vocabularies. Such vocabularies are used throughout the caBIG federation, both to code biomedical information and underpin the semantics of information that is exchanged on caGrid. Mayo brings extensive experience in terminology development and management, and has in-depth technical knowledge of LexBIG, Semantic Media Wiki, and Protégé—the key tools in the caBIG vocabulary domain. Semantic Bits will develop the online resources, including the knowledge base, that delivers these vocabulary resources to those who want to build their own interoperable tools and systems. 

NCI will shortly award an additional Knowledge Center for Data Sharing and Intellectual Capital. Achieving technical interoperability in and of itself will not deliver the full benefits of accelerated translational research and expedited care for the patient. These are only possible when researchers and oncologists have the information they need to do their work better. However, there are very important non-technical considerations, such as patient privacy protections and intellectual property interests, which affect the ability to make data available. caBIG™ is developing policies, processes, model agreements, and other materials to facilitate data sharing with appropriate protections.  This Knowledge Center will both continue and extend this work and provide resources to organizations that want to adopt or adapt these materials to streamline their own processes.

Support Service Providers

Support Service Providers are third party organizations that deliver software application and technical support to end-users and IT professionals, establishing fee-for-service agreements with each client.   NCI intends to announce in Summer, 2008, specific Support Service Providers selected for their demonstrated ability to provide accurate and up-to-date support services for caBIG™ tools, standards, and infrastructure.  They will offer Help Desk support, adaptation and enhancement of caBIG™-compatible software applications, deployment support for caBIG™ software applications, and documentation and training materials and services.

Program Offices

Program Offices are teams established at organizations to facilitate, coordinate, and expedite the caBIG™ adoption process across programs within an organization or between organizations. These offices leverage existing essential activities to promote broad integration of caBIG™ technologies. They serve as a liaison between the programs, end-users, institutional leaders, and IT administrators to help address cross-cutting biomedical opportunities.

All together, these programs of the ESN will support the needs of the current caBIG™ community, the broader cancer research enterprise, and potentially, the biomedical community as a whole that wish to adopt caBIG™ standards, applications, and infrastructure.  By helping extend the reach of caBIG™ tools, standards, and infrastructure in the biomedical research community, the ESN will be a crucial enabler of innovative research and improved patient outcomes.

Visit http://cabig.nci.nih.gov/esn/ to learn more about the Enterprise Support Network.

Media contacts

Alex Lyda, (212) 305-0820, mal2133|_at_|columbia|_dot_|edu

 

Belinda Mager, (212) 305-5587, bem9048|_at_|nyp|_dot_|org

ONE OF THE NATION'S LARGEST PORTFOLIOS OF NEW LYMPHOMA
THERAPIES TARGETS DIVERSE AND DIFFICULT CANCER

Herbert Irving Comprehensive Cancer Center at NewYork-Presbyterian Hospital
and Columbia University Medical Center Expands Lymphoma Program

NEW YORK, April 24, 2008 – The fifth leading cause of cancer in the United States, lymphoma is made up of more than 40 rare and highly diverse diseases that target the body’s lymphatic system. Lymphomas include both one of the fastest growing cancers — Burkitt’s lymphoma, which can double in size in as little as a day — and one of the slowest, chronic lymphocytic leukemia (CLL).

While all lymphoma types can be cured or managed as a chronic disease, its complexity and variation do not allow for a one-size-fits-all treatment approach. Instead, it necessitates highly specialized and individualized approaches.

With a dozen new therapies in development — one of the largest portfolios of lymphoma drugs under development anywhere — the Herbert Irving Comprehensive Cancer Center of NewYork-Presbyterian Hospital and Columbia University Medical Center is meeting this challenge with highly effective new treatments for the disease, giving hope to the more than one million lymphoma patients worldwide.

In 2006, NewYork-Presbyterian/Columbia recruited Dr. Owen A. O’Connor, one of the world’s top lymphoma researchers, to lead its Lymphoid Development and Malignancy Program, and direct more than 25 full-time scientists and physician scientists.

“By increasing the number and quality of treatment options for lymphoma patients, we are improving their chances for survival. This is especially critical for patients who haven’t responded to standard therapies,” says Dr. O’Connor, who is also chief of the Lymphoma Service at NewYork-Presbyterian/Columbia and associate professor of medicine at Columbia University College of Physicians and Surgeons.

One of the most promising new therapies developed at NewYork-Presbyterian/Columbia is PDX (pralatrexate) for T-cell lymphoma — among the most fatal forms of the disease. The drug is uniquely designed to camouflage itself as a folic acid, which allows it to be absorbed by the tumor, where it attacks the cancer. The therapy has been shown effective in 54 percent of patients who did not respond to other treatments. The drug is now being evaluated around the world, and if its activity is confirmed, it may get regulatory approval some time next year.

“Our hope is that the national multi-center clinical trial that is currently underway to evaluate this drug will result in an improved treatment option for patients,” says Dr. O’Connor, who has played a leading role in developing the drug.

Researchers are also exploring novel lymphoma treatments that are not chemotherapies. These include drugs targeting Bcl-6, a gene cloned by Dr. Riccardo Dalla-Favera in 1993, and an enzyme known as histone deacetylase. Work by Dr. Dalla-Favera has shown that drugs affecting these two targets will markedly synergize with conventional chemotherapy, and may lower the amount of chemotherapy necessary to achieve remission. 

“We are very excited about the promise of these new therapies. Our lymphoma program includes some of the nation’s brightest scientists working together to translate laboratory discoveries into improved treatment options for patients,” says Dr. Dalla-Favera, who is director of the Herbert Irving Comprehensive Cancer Center at NewYork-Presbyterian/Columbia, director of the Institute of Cancer Genetics at Columbia University Medical Center and Uris Professor of Pathology and Genetics & Development at Columbia University College of Physicians and Surgeons.

Investigators at NewYork-Presbyterian/Columbia also collaborate with colleagues at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, including Dr. John Leonard.

For more information about lymphoma treatments, contact the Herbert Irving Comprehensive Cancer Center at 212-305-3653.

Lymphoma is a type of cancer that originates in lymphocytes, a type of white blood cell in the vertebrate immune system. The most common type of lymphoma, non-Hodgkin’s lymphoma (NHL) includes B-cell lymphoma and T-cell lymphomas. Since the early 1970s, incidence rates of NHL have nearly doubled. The overall five-year survival rate is only 59 percent. Hodgkin’s lymphoma (HL), also known as Hodgkin’s disease, is a less common form of lymphoma that arises from an abnormal lymphocyte. The overall five-year survival rate is 85 percent. HL occurs mainly in young adults, with a peak occurrence between ages 16 and 34. Older patients, especially those over age 55, may also develop the disease. Treatments for lymphoma may include radiation therapy, chemotherapy, immunotherapy and bone-marrow or peripheral blood transplants.

The Herbert Irving Comprehensive Cancer Centerat Columbia University Medical Center and NewYork-Presbyterian Hospital encompasses pre-clinical and clinical research, treatment, prevention and education efforts in cancer. The Cancer Center was initially funded by the NCI in 1972 and became a National Cancer Institute (NCI)–designated comprehensive cancer center in 1979. The designation recognizes the Center’s collaborative environment and expertise in harnessing translational research to bridge scientific discovery to clinical delivery, with the ultimate goal of successfully introducing novel diagnostic, therapeutic and preventive approaches to cancer. For more information, visit www.hiccc.columbia.edu.

Columbia University Medical Center provides international leadership in basic, pre-clinical and clinical research, in medical and health sciences education, and in patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians & Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Established in 1767, Columbia’s College of Physicians & Surgeons was the first institution in the country to grant the M.D. degree. Among the most selective medical schools in the country, the school is home to the largest medical research enterprise in New York State and one of the largest in the country. For more information, please visit www.cumc.columbia.edu.

NewYork-Presbyterian Hospital, based in New York City, is the nation’s largest not-for-profit, non-sectarian hospital, with 2,242 beds. The Hospital has nearly a million patient visits in a year, including more than 230,000 visits to its emergency departments — more than any other area hospital. NewYork-Presbyterian provides state-of-the-art inpatient, ambulatory and preventive care in all areas of medicine at five major centers: NewYork-Presbyterian Hospital/Weill Cornell Medical Center, NewYork-Presbyterian Hospital/Columbia University Medical Center, Morgan Stanley Children’s Hospital of NewYork-Presbyterian, NewYork-Presbyterian Hospital/Allen Pavilion and NewYork-Presbyterian Hospital/Westchester Division. One of the largest and most comprehensive health-care institutions in the world, the Hospital is committed to excellence in patient care, research, education and community service. It ranks sixth in U.S.News & World Report’s guide to “America’s Best Hospitals,” ranks first on New York magazine’s “Best Hospitals” survey, has the greatest number of physicians listed in New York magazine’s “Best Doctors” issue, and is included among Solucient’s top 15 major teaching hospitals. The Hospital’s mortality rates are among the lowest for heart attack and heart failure in the country, according to a 2007 U.S. Department of Health and Human Services (HHS) report card. The Hospital has academic affiliations with two of the nation’s leading medical colleges: Weill Cornell Medical College and Columbia University College of Physicians and Surgeons. For more information, visit www.nyp.org.

- # # # -

Cancer Center member, Carol Prives, and two other Columbia faculty are named.

Link to National Academies News Release

Image-Guided Therapy Expert to Lead Combined Radiation Oncology at Columbia University College of Physicians & Surgeons, Weill Cornell Medical College, NewYork-Presbyterian Hospital.

External Link to CUMC News

Media Contact:

Elizabeth Streich (212) 305-3900; eas2125|_at_|columbia|_dot_|edu

Patient Queries:

Those interested in enrolling in this study should contact study coordinator Melissa Laudano at (212) 305-6665.

Half of Patients Do Not Respond to First-Line Chemotherapy;

Investigational Therapy May Prevent Surgical Removal of Bladder

Recruiting Participants for Ongoing Study of Treatment With
Breast-Cancer-Drug Abraxane® for Bladder Cancer

Study Conducted at the Herbert Irving Comprehensive Cancer Center at
NewYork-Presbyterian Hospital and Columbia University Medical Center

NEW YORK (Feb. 26, 2008) -- As many as half of patients with superficial bladder cancer do not respond to the standard first-line chemotherapy placed into the bladder, according to current multi-center outcomes data. When this happens, typically, their only option is surgical removal of the bladder. Now, researchers at the Herbert Irving Comprehensive Cancer Center of NewYork-Presbyterian Hospital and Columbia University Medical Center are investigating an FDA-approved metastatic breast-cancer drug called Abraxane® that may prove a safe and effective alternative to surgery for these patients.

Bladder cancer is the fourth leading cause of cancer in men and the ninth leading cause of cancer in women in the United States. In a given year, more than 60,000 new cases are diagnosed, and 13,000 will die from the disease.

"When the standard treatment does not work, currently the only option is surgical removal of the bladder -- something that, for all patients, is unappealing, and for some sicker patients is not even possible. With this study, we hope to find an effective second line medical option for these patients," says Dr. James McKiernan, director of urologic oncology at the Herbert Irving Comprehensive Cancer Center at NewYork-Presbyterian Hospital and Columbia University Medical Center, and vice chairman of the Department of Urology and assistant professor of urology at Columbia University College of Physicians and Surgeons.

The Phase I/II study will follow 18 patients for six weeks to assess dosage safety, followed by a second group of 19 patients who will be followed for six weeks to measure the effectiveness of the therapy.

The study is open to patients with recurrent bladder cancer that has not responded to standard therapy -- BCG (bacillus Calmette-Guerin) treatment.

In 2006, Dr. McKiernan, together with departmental chair Dr. Mitchell C Benson, led a phase I study of the drug Taxotere, also used to treat breast cancer, on a similar patient population, finding the drug to be safe with 12 of 18 patients responding (results were published in the July 1, 2006, Journal of Clinical Oncology). Since then, a favorable percentage of patients have survived with intact bladders.

Abraxane, he believes, will show similar or better results. "Abraxane has an analogous structure to Taxotere, but has the advantage of being more soluble due to its solvent-free formulation allowing for administration at higher concentrations," says Dr. McKiernan. "In one study of Abraxane for metastatic breast cancer, the drug successfully shrank tumors and had few side effects."

The study is funded by Abraxis Bioscience of Los Angeles, California.

Those interested in enrolling in this study should contact Dr. McKiernan, Dr. Benson or study coordinator Melissa Laudano at (212) 305-6665.

Herbert Irving Comprehensive Cancer Center
The Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center and NewYork-Presbyterian Hospital encompasses pre-clinical and clinical research, treatment, prevention and education efforts in cancer. The Cancer Center was initially funded by the NCI in 1972 and became an National Cancer Institute (NCI)-designated comprehensive cancer center in 1979. The designation recognizes the Center’s collaborative environment and expertise in harnessing translational research to bridge scientific discovery to clinical delivery, with the ultimate goal of successfully introducing novel diagnostic, therapeutic and preventive approaches to cancer.

NewYork-Presbyterian Hospital
NewYork-Presbyterian Hospital -- based in New York City -- is the nation’s largest not-for-profit, non-sectarian hospital, with 2,242 beds. It provides state-of-the-art inpatient, ambulatory and preventive care in all areas of medicine at five major centers: NewYork-Presbyterian Hospital/Weill Cornell Medical Center, NewYork-Presbyterian Hospital/Columbia University Medical Center, Morgan Stanley Children’s Hospital of NewYork-Presbyterian, NewYork-Presbyterian Hospital/Allen Pavilion and NewYork-Presbyterian Hospital/Westchester Division. One of the largest and most comprehensive health-care institutions in the world, the Hospital is committed to excellence in patient care, research, education and community service. It ranks sixth in U.S.News & World Report’s guide to "America’s Best Hospitals," ranks first on New York magazine’s "Best Hospitals" survey, has the greatest number of physicians listed in New York magazine’s "Best Doctors" issue, and is included among Solucient’s top 15 major teaching hospitals. The Hospital is ranked with among the lowest mortality rates for heart attack and heart failure in the country, according to a 2007 U.S. Department of Health and Human Services (HHS) report card. The Hospital has academic affiliations with two of the nation’s leading medical colleges: Weill Cornell Medical College and Columbia University College of Physicians and Surgeons. For more information, visit www.nyp.org

Columbia University Medical Center provides international leadership in basic, pre-clinical and clinical research, in medical and health sciences education, and in patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, nurses, dentists, and public health professionals at the College of Physicians & Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Established in 1767, Columbia’s College of Physicians & Surgeons was the first institution in the country to grant the M.D. degree. Among the most selective medical schools in the country, the school is home to the largest medical research enterprise in New York State and one of the largest in the United States. For more information, please visit www.cumc.columbia.edu.

#  #  #

Venkatraman E. Seshan, Ph.D., joined Columbia University Medical Center in July, 2007, as Professor of Biostatistics in the Department of Biostatistics at the Columbia University Mailman School of Public Health and the Director of the Cancer Center’s Biostatistics Shared Resource (BSR).

Dr. Seshan received his undergraduate and masters degrees (1985, 1987) from the Indian Statistical Institute and his Ph.D. in Statistics from Stanford University in 1992. He studied the problem of estimating multiple change-points under the guidance of Prof. David Siegmund. He began his post-doctoral statistical career as an Assistant Professor in the Department of Statistics at the University of Arizona in Tucson. In 1993 he joined the Department of Epidemiology and Biostatistics at the Memorial Sloan-Kettering Cancer Center as a Clinical Assistant Biostatistician and rose through the ranks to become an Associate Member in 2002.

Dr. Seshan’s research interests are in the area of computer intensive nonparametric methods for the analysis of biomedical data. He has developed novels applications of resampling techniques in the areas of survival, analysis and ROC curve analysis and two stage designs for gene-disease association and vaccine trials. Of particular significance is the Circular Binary Segmentation algorithm he developed in collaboration with Dr. Adam Olshen, which is widely used for the analysis of array CGH data. He has also collaborated extensively with clinical and basic science colleagues and made significant contributions in the areas of Gynecologic Oncology, Medical Physics & Radiation Oncology, Thoracic Oncology and High Throughput Screening. He is an Associate Editor of Statistics and Probability Letters.

Dr. Seshan may be contacted at: 212-851-5190, 212-305-9399 or ves2111|_at_|columbia|_dot_|edu.

Whether a woman receives radiation after breast cancer surgery may be associated with certain characteristics of her surgeon, including sex and medical training, according to a study published online January 29 in the Journal of the National Cancer Institute.

Many breast cancer patients do not receive radiation after undergoing breast conservation surgery, despite the fact that this treatment is considered a standard of quality cancer care and has been shown to reduce breast cancer recurrence. Previous studies have shown that certain patient characteristics, such as a patient's race and distance from a radiation therapy facility, are associated with receiving post-surgical radiation. But it has been unclear whether physician characteristics also play a role in the quality of breast cancer care.

Dawn Hershman, M.D., M.S., of the Herbert Irving Comprehensive Cancer Center at Columbia University in New York and colleagues investigated whether surgeon characteristics were associated with a patient receiving radiation after breast cancer surgery. They identified and analyzed data on nearly 30,000 women aged 65 and older with breast cancer who were diagnosed between 1991 and 2002 and who received breast-conserving surgery. They also collected information on the 4,453 surgeons who operated on these women—including their sex, year of graduation, medical school location, patient volume, and type of medical degree.

About 75 percent of the women received radiation after surgery. Each year from 1991 to 2002, the proportion of women receiving radiation increased. Nonetheless, older women, black women, unmarried women, and those living outside urban areas were less likely to receive radiation. After adjusting for patient and tumor characteristics, the researchers found that women who received radiation were more likely to have a surgeon who was female, had an M.D. degree (compared to a D.O. degree), or was trained in the United States.

"Our study is one of the first to demonstrate associations between certain surgeon characteristics and quality of breast cancer care... If confirmed, more research is needed on whether they reflect surgeon behavior, patient response, or physician-patient interactions," the authors write.

Contact:

Dawn Hershman, (212)305-1945, dlh23|_at_|columbia|_dot_|edu

Citation:

Hershman DL, Buono D, McBride RB, Tsai WY, Joseph KA, Grann VR, Jacobson JS. Surgeon Characteristics and Receipt of Adjuvant Radiotherapy in Women With Breast Cancer. J Natl Cancer Inst 2008; 100:199–206

Release written by:

Liz Savage, Andrea Widener, jncimedia@oxfordjournals.org, 301-841-1287

Related Article in JNCI:

Surgeon Characteristics and Receipt of Adjuvant Radiotherapy in Women With Breast Cancer Dawn L. Hershman, Donna Buono, Russell B. McBride, Wei Yann Tsai, Kathy Ann Joseph, Victor R. Grann, and Judith S. Jacobson
J Natl Cancer Inst 2008 0: 3201-206. [Abstract] [Full Text]

Michael M. Shen, Ph.D., who joined Columbia University Medical Center in September 2007, is Professor of Medicine and Genetics & Development at Columbia University College of Physicians and Surgeons, is a member of the Cancer Center’s Prostate Cancer Program.

Dr. Shen received his undergraduate degree from Harvard University in 1984 and pursued his doctoral studies at the MRC Laboratory of Molecular Biology in Cambridge, England, receiving his Ph.D. degree from Cambridge University in 1988. Dr. Shen completed his post-doctoral training in the laboratory of Dr. Philip Leder in the Department of Genetics, Harvard Medical School. He was appointed Assistant Professor in the Department of Pediatrics at UMDNJ – Robert Wood Johnson Medical School in 1994, and rose to the rank of Professor before moving to Columbia University Medical Center in 2007.

Dr. Shen’s laboratory pursues basic and translational research in the areas of mammalian embryogenesis and stem cell differentiation, as well as development of the prostate gland and molecular mechanisms of prostate carcinogenesis. He is a member of the Editorial Boards of the journals Mechanisms of Development and Developmental Dynamics, and has served on scientific review panels for the National Institutes of Health.

Particular areas of research interest include studies of stem cell lines from the early mammalian embryo, molecular analyses of prostate stem cells and cancer stem cells, and generation of mouse models of prostate cancer and metastasis.

Dr. Shen may be contacted at: mshen|_at_|columbia|_dot_|edu

Corinne T. Abate-Shen, Ph.D., who joined Columbia University Medical Center in September 2007, is Professor and Director of Research in the Department of Urology at Columbia University College of Physicians and Surgeons, and a member of the Cancer Center’s Prostate Cancer Program.

Dr. Abate- Shen attended graduate school at Cornell University Medical College, obtaining her Ph.D. in Neurobiology in 1987. Dr. Abate-Shen pursued her postdoctoral training with Tom Curran at the Roche Institute of Molecular Biology. Her highly productive post-doctoral career included seminal observations on the redox regulation of the protooncoproteins Fos and Jun, which inspired many subsequent studies on the redox control of other transcriptional regulatory proteins.

In 1991 Dr. Abate-Shen joined the Department of Neuroscience and Cell Biology and the Center for Advanced Biotechnology and Medicine, UMDNJ-Robert Wood Johnson Medical School as an Assistant Professor. She rose to the rank of Professor by 2001, and was appointed Chief of a new Division in the Department of Medicine in 2002. In addition, Dr. Abate-Shen created the Prostate Program for the Cancer Institute of New Jersey and served as its co-leader from 1999 until moving to Columbia University Medical Center.

Dr. Abate-Shen’s research focuses on the molecular mechanisms of homeobox genes in development and cancer. Her major research interests have included deciphering the molecular bases of homeoprotein specificity, and her laboratory has recently contributed groundbreaking insights regarding the fundamental question of how homeoproteins achieve target gene recognition in vivo. Furthermore, her interests in elucidating the roles of homeobox genes in cancer have led to the development of mouse models of prostate cancer that have been widely utilized for investigating the molecular basis of prostate tumorigenesis as well as pre-clinical models for intervention and therapy.

Dr. Abate-Shen is a member of the NCI Board of Scientific Counselors, she serves on the editorial board of Molecular and Cellular Biology and is an Associate Editor of Cancer Research, and she has recently been appointed Deputy Editor of AACR’s new journal Cancer Prevention Research.

Dr. Shen may be contacted at: 212-851-4731 or cabateshen|_at_|columbia|_dot_|edu.

MEDIA CONTACT: Elizabeth Streich, 212-305-6535; eas2125|_at_|columbia|_dot_|edu

NEW STUDY REVEALS FOR FIRST TIME HOW BRCA1 MUTATIONS
CAUSE BREAST CANCER 

Finding Implicates Tumor Suppressor Gene, PTEN
Columbia University Medical Center among
Two Institutions to Identify this Gene in 1997;

Discovery Opens New Pathway for Treatment of
Highly Aggressive Form of Breast Cancer

NEW YORK (Dec. 9, 2007) – An international team of researchers led by Columbia University Medical Center’s Herbert Irving Comprehensive Cancer Center and Sweden’s Lund University has, for the first time, revealed how mutations in the BRCA1 gene lead to breast cancer. Findings show that one way BRCA1 mutations cause cancer is by knocking out a powerful tumor suppressor gene known as PTEN.

Ramon Parsons,
M.D., Ph.D.

The new study was published online on the Nature Genetics website on Dec. 9, 2007: http://www.nature.com/ng. It will appear in the January print issue of this journal. The study was led by Ramon Parsons, M.D., Ph.D., the Avon Foundation Professor of Medicine and Pathology in the Institute of Cancer Genetics at Columbia University College of Physicians and Surgeons and Åke Borg, Ph.D., professor of oncology at Lund University. The paper’s first author was Lao Saal, Ph.D. (now finishing his medical degree at Columbia University College of Physicians and Surgeons).

These findings are exciting because ever since the link was established between BRCA1 and breast cancer more than 10 years ago, we have been frustrated by our lack of understanding about how mutations in this gene cause breast cancer. We have been stymied by our limited resources to treat these cancers, which are associated with very poor prognoses. Now that we know that PTEN is involved, we finally have a target for therapy for these cancers,” said Dr. Parsons, the study’s corresponding author. Dr. Parsons is director of the Avon Foundation Breast Cancer Research Laboratory and leader of the Herbert Irving Comprehensive Cancer Center's Breast Cancer Program.

Lao Saal, Ph.D.

In 1997, Dr. Parsons led one of the two teams that independently discovered the PTEN, one of the most important tumor suppressor genes altered in breast cancer, as well as in brain and prostate cancers. PTEN is now recognized to be mutated in about 30 percent of all cancers, making it the second most mutated gene in cancer after p53. Knocking out PTEN sends a strong pro-growth signal on tumor cells. This is unlike the BRCA1 mutation, which only predisposes the cells to accumulate genetic damage and sends an indirect signal for cell growth. “Once a cell loses PTEN, it has a growth advantage over its neighbors and starts on the road to cancer,” said Dr. Parsons.

PTEN mutations promote runaway tumor cell growth by increasing the activity of a series of different proteins in the cell known as the PTEN/PI3K pathway. Shutting down any one of those proteins could potentially stop growth of the cancer. Investigational therapies to shut down proteins in the PTEN pathway are currently in Phase I clinical trials

How the BRCA1 Mutation Mechanism Was Pinpointed

Dr. Parsons and his research team made the connection between BRCA1 and PTEN using techniques to search for physical chromosome breaks within the PTEN gene – a technique that had never before been used. Previous searches for PTEN mutations in BRCA1 tumors had looked for conventional mutations and failed to turn up any abnormalities.

The researchers scanned 34 biopsies taken from women with BRCA1 tumors. The PTEN gene had been split in two, but inadequately repaired in about one-third of the cancers. In some cases, entire sections of the gene were missing; in others, one-half of the gene was reattached to other regions on the chromosome.

These types of large chromosomal mistakes stem directly from the tumor’s lack of BRCA1, a gene that is normally involved in the repair of such damage. In breast cancers from women with normal BRCA1, such large mutations in PTEN were rarely detected.

Finding May Affect 50% of BRCA1 Breast Cancers & Lead to New Treatments

Dr. Parsons estimates that about 50 percent of BRCA1 breast cancers will be found to harbor mutated PTEN once a complete analysis of chromosomal mutations is done.

Breast cancer tumors caused by BRCA1 are known as basal-like or triple-negative because these tumors usually lack estrogen, progesterone, and HER2 receptors, which are needed for most breast cancer treatments to be effective. Basal-like breast tumors are found in 10 to 20 percent of women with non-hereditary breast cancer (meaning, not caused by a genetic mutation in BRCA1 or another gene), and the researchers found that PTEN is also lost in the majority of these breast tumors as well.

Our results point to PTEN as a major player in both hereditary and non-hereditary basal-like breast cancer, a finding that may now be exploited to develop new therapeutic strategies to improve outcomes for women with these aggressive tumors,” said Dr. Saal, who at the time of the research, was a fellow in Dr. Parsons’ Avon Foundation Breast Cancer Research Laboratory.

The researchers also predict that other cancer genes besides PTEN are targeted by BRCA1. “By using the same techniques we used to find gross chromosomal rearrangements in PTEN, we hope to start identifying additional mutated genes involved in the development of breast cancer,” said Dr. Parsons.

These kinds of mutations that break tumor suppressors in half may turn out to be common in many kinds of carcinomas, particularly those with deficiencies in DNA repair pathways similar to BRCA1, a question that only a systematic search can answer,” said Dr. Saal.

Similar research is underway in tumors from carriers of germline mutations in BRCA2, the other known major breast cancer susceptibility gene,” said Dr. Borg. “BRCA2 has a role downstream in the same DNA double strand break repair pathway as BRCA1, but tumors from BRCA2 mutation carriers have a quite different phenotype compared to BRCA1 tumors, less often involving PTEN loss. However, like BRCA1, BRCA2 tumors have an instable genome with massive chromosomal aberrations, suggesting that other genes may be targeted.”

Breast Cancers Caused by BRCA1 Mutations are Especially Lethal & Difficult to Treat

Basal-like breast cancer tumors, whether caused by BRCA1 mutations or of the non-hereditary type, are among the most aggressive tumors – they grow fast and spread quickly, making them more likely than other types of cancer to be fatal. These tumors are more likely to be resistant to standard breast cancer treatments, such as Tamoxifen or Herceptin, making them especially difficult to treat. As a result, many young BRCA1 carriers opt to have their breasts prophylactically removed instead of waiting for cancer to appear.

Breast cancers caused by BRCA1 mutations tend to affect women much earlier – often before menopause and sometimes in their 20s and 30s – and between 60 and 80 percent of women who carry a BRCA1 mutation will develop breast cancer at some point during their lives. BRCA1 mutation carriers are most common among African-American women and women of Ashkenazi Jewish descent. Inherited BRCA1 (and BRCA2) mutations also predispose women to ovarian cancer, a disease that frequently escape early diagnosis and which has a fatal outcome in advanced stages.

International Collaborations & Research Support

Additional Columbia researchers involved in the study include Hanina Hibshoosh, M.D., associate professor of clinical pathology and Vundavalli Murty, M.D., associate professor of pathology in the Institute for Cancer Genetics and Herbert Irving Comprehensive Cancer Center, and others.

“Identifying these rearrangements would not have been possible without the support of the shared resources of the Herbert Irving Comprehensive Cancer Center and our collaboration with Drs. Borg, Saal, Hibshoosh and Murty,” said Dr. Parsons.

This research was supported, in part, by the Avon Foundation, the OctoberWoman Foundation, and the National Cancer Institute and the Swedish Cancer Society.

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The Avon Foundation Breast Cancer Research Laboratory at Columbia University Medical Center is a state-of-the-art facility that aims to better understand genetic pathways involved in breast cancer, and how to control these to prevent or stop the progression of cancer. The laboratory is under the leadership of Ramon Parsons, M.D., Ph.D., leader of the Breast Cancer Program of the Herbert Irving Comprehensive Cancer Center of Columbia University Medical Center and NewYork-Presbyterian Hospital.

The Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center and NewYork-Presbyterian Hospital encompasses basic, pre-clinical and clinical research, treatment, prevention and education efforts in cancer. The Cancer Center was initially funded by the NCI in 1972 and became an NCI-designated comprehensive cancer center in 1979. The designation recognizes the Center’s collaborative environment and expertise in harnessing translational research to bridge scientific discovery to clinical delivery, with the ultimate goal of successfully introducing novel diagnostic, therapeutic and preventive approaches to cancer. http://www.hiccc.columbia.edu/

Columbia University Medical Center provides international leadership in basic, pre-clinical and clinical research, in medical and health sciences education, and in patient care. The medical center trains future leaders and includes the dedicated work of many physicians, public health professionals, dentists, nurses, and scientists at the College of Physicians & Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. http://www.cumc.columbia.edu

The Herbert Irving Comprehensive Cancer Center recently recruited three renowned cancer physician-scientists. “Dr. Edward Gelmann, Dr. Carlos Cordon-Cardo and Dr. Owen O’Connor each bring expertise in important clinical and research areas and will spur the development and expansion of the HICCC,” says Riccardo Dalla-Favera, Uris Professor of Pathology and Genetics & Development, director of the Institute of Cancer Genetics and director of the Herbert Irving Comprehensive Cancer Center. Read full story in InVivo