LA JOLLA, Calif., Feb. 8, 2022 /PRNewswire-PRWeb/ -- New research
from Sanford Burnham Prebys has revealed significant molecular
differences between the breast cells of white and Black women that
help explain why Black women experience higher breast cancer
mortality. The findings, published February
8 in the journal Therapeutic Advances in Medical Oncology,
suggest that changing current diagnostic and treatment strategies
could help address the disparity.
"The way each human being responds to cancer treatment is
influenced by so many internal and external factors that are unique
to each of us," says Svasti Haricharan, Ph.D., an assistant
professor at Sanford Burnham Prebys. "The scientific community has
to confront this and invest time and money into understanding it,
because everybody deserves care that is tailored to their molecular
makeup as closely as possible."
Haricharan and her team found significant differences between
white and Black women in the way DNA repair genes are expressed,
both in healthy breast tissue and in tumors that are positive for
the estrogen receptor (ER+), which make up one of the most common
forms of breast cancer. These molecular differences also
corresponded with changes in how quickly cancer cells in the breast
can grow.
"What we're seeing here is a tangible molecular difference in
how these cells repair damaged DNA—a critical factor in the
development of cancer—which affects how cells grow and reproduce in
tumors," says Haricharan.
- Black women with breast cancer: Worse outcomes, less
research
Black people have the highest cancer mortality rate of any
racial or ethnic group. Among Black women, breast cancer makes up
about a third of all cancer diagnoses, with ER+ breast cancer being
the most common. Black women with ER+ breast cancer are 42% more
likely to die of the disease than white women, and while there are
lifestyle and socioeconomic factors that contribute to this
disparity, such as access to healthcare, they are not enough to
fully account for the difference.
"Society has internalized the narrative that lifestyle factors
are to blame for racial differences in health outcomes, so most
scientists don't look at molecule-level differences between
people," says Haricharan "It also makes people who are sick feel
they are somehow at fault because of how they're living their
lives. Now we're seeing that it's so much more complicated than
that."
One barrier to fully exploring the disparities between white and
Black women with breast cancer is the historical lack of data on
non-white patients.
"Black women are severely underrepresented in virtually all
datasets of patient tumors, so a lot of previous results about
breast cancer only accurately reflect what's happening to white
women," says Haricharan. "We hope our research will highlight the
need to study cancer in different racial and ethnic groups more
closely and improve outcomes for historically marginalized
patients."
- Black women's cells repair DNA differently
DNA repair is a fundamental part of normal cellular function,
regulating processes throughout the cell and helping them recover
from the errors that occur naturally during DNA replication or in
response to external factors like stress. Unlike healthy cells,
cancer cells often acquire genetic changes that make it impossible
for them to repair DNA, which can make these cells resistant to
treatment.
"We've already seen how defects in DNA repair lead to treatment
resistance in breast cancer. But until now, there weren't studies
to measure the degree to which this differs in Black versus white
women or what's driving that difference," Haricharan says.
To fill this gap, the researchers looked at both healthy and
tumor tissue from 185 Black women and compared these to samples
from white women. They found that eight genes powering DNA repair
are expressed differently in Black women. They also found
consistent molecular differences in the cellular signals
controlling how fast cells can grow.
Notably, these differences were not confined to cancer
cells—even healthy tissue showed a different gene expression
pattern in Black versus white women.
"This is so important because if the normal tissue is different
at the molecular level based on race or ethnicity, then everything
we understand about how each of us responds to cancer treatment is
going to be different as well," adds Haricharan.
- Toward better precision medicine
The study demonstrates how precision medicine for ER+ breast
cancer could be quickly and easily improved by taking ancestry into
account when prescribing treatments. Specifically, the findings
suggest that Black women may benefit from earlier treatment with
CDK inhibitors, a class of drug that helps stop cancer cells from
multiplying by blocking biochemical signals called cyclin-dependent
kinases (CDKs).
Current clinical guidelines for the use of CDK inhibitors
suggest that they be used only after seeing progress in standard
endocrine therapy, which means that for some women, by the time
they receive CDK inhibitors, their disease has progressed too far.
The team found that there are significantly higher levels of one
type of CDK in the tumor tissue of Black women, suggesting that at
least a subset of Black women may benefit from earlier treatment
with CDK inhibitors.
"This is something we can act upon immediately, because helping
these women is less about finding a new drug and more about
changing the timing for treatments we already have available," says
Haricharan.
In a broader sense, the study highlights the critical need for
more inclusive biomedical research that understands and respects
the need for representing the unique biology of each patient when
building datasets and forming hypotheses to test in the lab.
"The more we look for differences between groups, the more we're
going to find," says Haricharan. "We need to build better datasets
so we can stop considering what we observe in white people as the
default for all biology, which creates a fundamental inequity in
biomedical progress."
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Additional authors on the study include Aloran Mazumder, Ph.D.,
and Athena Jimenez, B.A., Sanford
Burnham Prebys Medical Discovery Institute; Rachel E. Ellsworth, Ph.D., Henry M. Jackson
Foundation for the Advancement of Military Medicine; Stephen J. Freedland, Ph.D., M.D., Cedars-Sinai
Medical Center and Durham VA Medical Center; Sophia George, Ph.D., University of Miami; and Matthew N. Bainbridge, Ph.D., Rady Children's
Institute of Genomic Medicine.
The researchers were supported by the National Institutes of
Health (award numbers P30CA030199 and CA229613), the Department of
Defense (award number W81XWH-18-1-0034) and Susan G. Komen (award number CCR18548157).
About Sanford Burnham Prebys Medical Discovery Institute
Sanford Burnham Prebys is a preeminent, independent biomedical
research institute dedicated to understanding human biology and
disease and advancing scientific discoveries to profoundly impact
human health. For more than 40 years, our research has produced
breakthroughs in cancer, neuroscience, immunology and children's
diseases, and is anchored by our NCI-designated Cancer Center and
advanced drug discovery capabilities. For more information, visit
us at http://www.SBPdiscovery.org or on Facebook at
facebook.com/SBPdiscovery and on Twitter @SBPdiscovery.
Media Contact
Miles Martin, Sanford Burnham
Prebys, 858 539 3042, mmartin@sbpdiscovery.org
SOURCE Sanford Burnham Prebys