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The evolving tumor
"The traditional approach to treating women with metastatic breast disease begins by looking at the characteristics of their original, primary tumor," says Nancy Lin, MD, of the Breast Oncology Center at Dana-Farber and a member of the new research team. "Did the first tumor grow in response to estrogen? Was it susceptible to the drug Herceptin (which blocks an overactive growth factor in some breast cancers)? Treatment for the recurrent cancer would be based on those criteria."
Metastasis:
When breast cancers spread, their most common destination is the liver, bones, or lungs.
Illustration by Irina Zlobina
While that approach is sensible, it assumes that the resurgent tumor and the primary one are functionally and genetically the same. Now that investigators can scan tumors' genetic activity, they can find out if that assumption is justified, or if tumors change their genetic "signatures" as they spread, potentially making the tumors vulnerable to specific treatments.
"Tracking gene-activity changes may help us understand why some women with breast cancer have no recurrence of the disease, while others do," Dr. Lin remarks. "If we can predict which women are likely to have metastasis, we may be able to identify the best candidates for aggressive treatment, as well as those who require less."
The research can also help determine if breast cancers contain clues about their likely destination, be it the lungs, bones, liver, or other organ. "We want to know if tumors that spread to one organ are genetically different from those that spread to another, and if we can tailor treatments to those differences," Dr. Lin explains.
The new project teams three sets of experts: Surgeons and interventional radiologists (who have special training in X-ray-guided procedures) will obtain tumor samples from women with metastatic breast cancer, while scientists trained in cancer genetics and molecular biology will measure and compare tumors' genetic activity patterns. Patients who participate in the project will have tumor tissue samples collected from the primary cancer and from sites where the disease has spread. Samples will be analyzed using "gene chips" or "microarrays" to search for changes in gene expression—the amount of activity—associated with metastatic growth. Ultimately, the hope is to design and test drugs targeted at such alterations.
"Someday we may have the capability to test living cancer cells from women with metastatic disease for susceptibility to particular classes of available drugs," says J. Dirk Iglehart, MD, director of the Women's Cancers Program at Dana-Farber and chief of Surgical Oncology at Brigham and Women's Hospital. "In the meantime, classifying tumors according to genetic signature will speed the process of matching specific medications to specific tumors."
A second arm of the research will focus on patients' quality of life. Through counseling and questionnaires, "we'll study how a breast cancer diagnosis affects women's outlook, their ability to work, take care of their families, and pursue the activities that are most important in their lives," says Eric Winer, MD, director of the Breast Oncology Center at Dana-Farber and one of the leaders of the project.
He adds, "Of course, the most important goal of the research is to make sure that women will not have to face a diagnosis of metastatic breast cancer in the next 10-15 years. If we eliminate the problem, we will not have to worry about its impact on quality of life."
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