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