July 8, 2008 - Young women's breast cancers tend to
be more aggressive and less responsive to treatment than the cancers
that arise in older women, and researchers at the Duke Comprehensive
Cancer Center and the Duke Institute for Genome Sciences & Policy may
have discovered part of the reason why: young women's breast cancers
share unique genomic traits that the cancers in older women do not
exhibit.
"Clinicians have long noted that the breast cancers
we see in women under the age of 45 tend to respond less well to
treatment and have higher recurrence rates than the disease we see in
older women, particularly those over the age of 65," said Kimberly
Blackwell, M.D., a breast oncologist at Duke and senior investigator on
the study.
"Now we're really understanding why this is the
case, and by understanding this, we may be able to develop better and
more targeted therapies to treat these younger women."
The results appear in the July 10 Journal of
Clinical Oncology. The study was funded by the National Cancer
Institute.
Duke researchers looked at samples of nearly 800
breast tumors from women in five countries on three continents, and
divided them into age-specific cohorts.
The investigators found more
than 350 sets of genes that were active only in the tumors from women
under age 45. Conversely, tumors arising in women over age 65 did not
share these activated gene sets.
"The breast tumors that arose in younger women
shared a common biology, and this discovery was truly remarkable,"
Blackwell said.
"The genes that regulate things like immune function,
oxygen supply and mutations that we know are related to breast cancer,
such as BRCA1, were preferentially expressed in the tumors taken from
younger women, but when we compared younger women's tumors to older
women's tumors, we found those same gene sets were not expressed in the
'older' tumors."
Researchers have already developed compounds that
target some of the activated gene expression pathways that the Duke team
discovered, and many of these compounds have promise for combating young
women's tumors, Blackwell said. Identifying these characteristic gene
expression profiles will be an important part of finding new therapies,
she said.
"Many of the gene sets we saw in 'younger' tumors
distinguished these cancers from 'older' tumors but the reverse was not
true -- there was nothing we saw in the older women's tumors that set
them apart genomically," Blackwell said. "Identifying these
distinguishing characteristics may be the first step in developing more
effective treatments for these younger patients."
Other researchers involved in this study include
Carey Anders, David Hsu, Gloria Broadwater, Chaitanya Acharya, John
Foekens, Yi Zhang, Yixin Wang, Kelly Marcom, Jeffrey Marks, Phillip
Febbo, Joseph Nevins and Anil Potti.
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