• February 2, 2009
    Protein biomarkers may guide breast cancer treatment

    garber.jpgJudy Garber, MD, MPH, director of the Cancer Risk and Prevention Program at Dana-Farber. 

    Dana-Farber researchers, working with a company founded to convert discoveries from Dana-Farber and MIT laboratories into practical benefits for cancer patients, have identified a set of proteins that may aid in the treatment of a particularly aggressive form of breast cancer.

    The findings, reported at the annual San Antonio Breast Cancer Symposium in December 2008, involve a form of breast cancer designated "triple-negative" because it doesn't respond to therapies that target cancer cells' receptors for estrogen, progesterone, or a growth signal called EGFR. The researchers – from Dana-Farber, Beth Israel Deaconess Medical Center, and the DNA Repair Company – sought to determine which proteins are used by such cells to repair DNA that has been damaged by chemotherapy. DNA damage normally causes cancer cells to die, but drug-resistant cancers find ways to fix themselves so they can continue growing and dividing.

    Investigators examined tumor samples from 143 patients with triple-negative cancer to see which DNA repair proteins affected the progress of the disease. In an analysis of half the samples, investigators found that patients whose tumor cells harbored four specific DNA repair proteins were apt to have their disease recur far more quickly than other patients. These findings were confirmed by measuring these proteins in the second group of patients.

    Patients whose tumors carried the four-protein combination had a median time of 14 months before their cancer recurred. In other patients, the median time for recurrence was more than 10 years.

    The findings suggest that DNA repair protein levels in patients with triple-negative breast cancer can indicate which patients are at greatest risk for rapid relapse and can benefit from additional therapy. The "pathways" by which such proteins influence one another may also be inviting targets for new therapies.

    "These findings provide intriguing evidence that the activity of certain DNA repair pathways plays an important role in determining how patients with triple-negative disease will respond to therapy," said senior investigator Judy Garber, MD, MPH, director of the Cancer Risk and Prevention Program at Dana-Farber. "Further validation will help focus drug development on approaches most likely to succeed. The frequently poor prognosis for patients with this form of breast cancer lends increased urgency for treatment and new drug development."

    The study's lead author is Brian Alexander, MD, a radiation oncology resident working with Alan D'Andrea, MD, leader of the Division of Genome Stability and DNA Repair in the Department of Radiation Oncology.

    – Rob Levy
    Robert_Levy@dfci.harvard.edu 

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