Gene Mutations in Breast Cancer Patients May Help Determine Treatment

Gene Mutations in Breast Cancer Patients May Help Determine Treatment

March 1, 2002, Fairfax, Va. -- Female breast cancer patients who possess a mutation in their ATM gene may be more likely to suffer breast tissue side effects from adjuvant radiation therapy than patients who do not have such a mutation, according to a new study published in the March 2002 issue of the International Journal of Radiation Oncology Biology and Physics.

In a study conducted under the leadership of Christopher M. Iannuzzi, M.D., a member of the department of radiation oncology at Mount Sinai Medical Center in New York, and Barry S. Rosenstein, Ph.D., the principal investigator for this project, 46 patients with early-stage breast carcinoma underwent limited surgery and adjuvant radiation therapy. Researchers were able to isolate DNA from the blood lymphocytes of the patients and then amplify each exon of the ATM gene using a polymerase chain reaction. Using a powerful new technique called denaturing high performance liquid chromatography (DHPLC), researchers were then able to identify variants in the ATM gene and determine if there existed a correlation between ATM mutation status and late radiation normal tissue effects.

Of the 46 patients, nine ATM mutations were identified in six patients. After a median follow-up time of 3.2 years, researchers discovered a significant correlation between ATM mutation status and Grade 3-4 subcutaneous late effects. Whereas only 3 (7 percent) of the 43 patients who did not develop this form of severe toxicity harbored the ATM mutation, all 3 of the patients (100 percent) who manifested Grade 3-4 subcutaneous late effects did possess the mutation. In fact, all three of the patients manifesting severe late subcutaneous responses actually harbored 2 ATM mutations.

"Possession of an ATM gene mutation, particularly when 2 mutations are present, may be predictive of an increase in subcutaneous late tissue effects after radiation therapy for breast cancer patients and may prove to be a relative contraindication to standard management," said Dr. Iannuzzi. "These patients may be better served with reduced doses of radiation but whether this will lead to equivalent local control rates remains to be tested."

"This study is too small to make definitive recommendations at this time. But if a larger study confirms these findings, then breast cancer patients may be well served by genetic screening prior to treatment to help facilitate the most appropriate radiotherapeutic protocol," added Dr. Iannuzzi. He says that a larger study is currently underway at his institution to confirm these findings.

To arrange an interview with the lead author of the study, Christopher M. Iannuzzi, M.D., please contact him at the Mount Sinai Medical Center at (212) 241-7500 or e-mail Dr. Iannuzzi at [email protected]. For more information or to obtain a copy of the study, please call Lesley Nevers at (703) 227-0141 or e-mail her at [email protected].

The International Journal of Radiation Oncology Biology and Physics is the official journal of the American Society for Therapeutic Radiology and Oncology. ASTRO is the largest radiation oncology society in the world, with 7,000 members who specialize in treating patients with radiation therapies. As a leading organization in radiation oncology, biology and physics, the society's goals are to advance the scientific base of radiation therapy and to extend the benefits of radiation therapy to those with cancer and other diseases.

Contact:Katherine Egan Bennett703-227-0156[email protected]

Lesley Nevers703-227-0141[email protected]

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