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Genetic researchers hunt down breast cancer clues 

 



Women today rely on mammography, routine physical exams from a doctor and their own breast self-exams to try to detect breast tumors. Still, despite women’s diligence, cancers often already have spread by the time they are found.

But if Melanie Palomares, M.D., M.S., has anything to do with it, women will someday have a blood test to detect breast cancer early, when it can be most successfully treated. Such a test could be useful both for the initial diagnosis of breast cancer and for the early detection of breast cancer recurrence.

Palomares, a City of Hope medical oncologist and epidemiologist in the Department of Clinical Cancer Genetics, has started a registry of breast cases at the Medical Center, aiming to gather blood specimens from 910 women with invasive breast cancer, as well as women with ductal carcinoma in situ and benign breast disease, diagnosed over the next five years.

Supported by a more than $694,000 grant from the U.S. Department of Defense, Palomares is working with City of Hope colleagues to scientifically sort through blood samples in search of the faintest signs of cancer. She began recruiting patients in November.
 
When the scientists analyze the blood samples, "we will be looking specifically for messages expressed by breast cancer cells and not by cells normally found in blood," Palomares said. In a way, it is like hunting for one specific, tiny jelly bean among thousands in a huge jar.

As Palomares explains it, researchers invite patients to participate in the study when the women visit the Rita Cooper Finkel & J. William Finkel Women’s Health Center for a breast biopsy –  usually done after a mammogram or physical exam detects a suspicious mass. The researchers take an initial blood sample from all participants.

If the biopsy indicates a participant has breast cancer, General Clinical Research Center staff members take a blood sample for study at regular intervals when the patient visits her City of Hope physician for follow-up care. Women also may receive a kit so that blood can be sampled at visits with community physicians. The researchers will track the participants' progress over 10 years.

Women with ductal carcinoma in situ, or DCIS, provide an initial blood specimen and are monitored with periodic questionnaires only, while women found with benign breast disease provide an initial blood specimen but only participate as controls in the study. Physicians also may refer their already-diagnosed breast cancer patients for the study, as long as they have not yet had systemic therapy. Interested women may also contact the study coordinator directly.

In this study, researchers will use real-time reverse transcriptase polymerase chain reaction, or RT-PCR. RT-PCR is a powerful technique in which DNA is produced from its complementary string of RNA. When performed using real-time techniques, it results in a quantitative laboratory test that is useful for following trends over time.
 
Palomares and colleagues hope to see whether performing RT-PCR with genetic material from blood can find key differences among women with invasive breast cancer, DCIS and benign breast disease. If so, such a test could be useful in diagnosis.

The researchers also are studying whether certain genetic markers in the blood can show how well a woman is responding to treatment. They want to know if the markers also can predict cancer relapse. Finally, they plan to perform exploratory studies to see whether novel nucleic acid and proteomics assays might be helpful in early detection, too.

"These tumor markers are complicated assays; the real time RT-PCR assay alone has been in development since 1998,” Palomares said.

The database will dovetail with the City of Hope Breast Cancer Program tumor bank, currently in development, and will eventually be linked to the National Comprehensive Cancer Network database at City of Hope, Palomares said.
 
Collaborators include clinicians George Somlo, M.D., Han Luu, M.D., Benjamin I. Paz, M.D., and Jeannie Shen, M.D., as well as Andrea Thornton, Ph.D., who will work on a quality-of-life study component. Scientists include Terry Lee, Ph.D., Steve Sommer, M.D., Ph.D., and the University of Washington’s Dan Sabath, M.D., Ph.D., Joyce Niland, Ph.D. and Doug Stahl, Ph.D., of Information Sciences/Biomedical Informatics, and David Smith, Ph.D., Paul Frankel, Ph.D., and Suzette Blanchard, Ph.D., of Biostatistics are also lending their expertise.

For more information on the Breast Cancer Tumor Marker study, please contact study coordinator Chi Vu at ext. 64826 (or from outside City of Hope, call 626-256-HOPE, ext. 64826).

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