Research reveals why more black women are dying
LA JOLLA, CA. – February 08, 2022 – New research from Sanford Burnham Prebys has revealed significant molecular differences between white and black women’s breast cells that help explain why black women experience higher breast cancer mortality. The results, published on February 8 in the journal Therapeutic advances in medical oncologysuggest that modifying current diagnostic and treatment strategies could help reduce the disparity.
“How each human responds to cancer treatment is influenced by many internal and external factors that are unique to each of us,” says Svasti Haricharan, Ph.D., assistant professor at Sanford Burnham Prebys. “The scientific community needs to face this and invest time and money to understand it, because everyone deserves care that is as tailored to their molecular makeup as possible.”
Haricharan and her team found significant differences between white and black women in how DNA repair genes are expressed, both in healthy breast tissue and in estrogen receptor positive (ER+) tumors. ), which is one of the most common forms of breast cancer. These molecular differences also corresponded to changes in the growth rate of breast cancer cells.
“What we see here is a tangible molecular difference in how these cells repair damaged DNA – a critical factor in cancer development – which affects how cells grow and reproduce in tumors,” explains Haricharan.
Black women with breast cancer: Worse outcomes, less research
Black people have the highest cancer death rate of any racial or ethnic group. Among black women, breast cancer accounts for 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 from the disease than white women, and while there are lifestyle and socioeconomic factors that contribute to this disparity, such than access to health care, they are not enough to fully explain 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 molecular-level differences between people,” says Haricharan. “It also makes sick people feel like they’re somehow at fault because of the way they live their lives. Now we see it’s so much more complicated than that.
A barrier to fully exploring 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 patient tumor datasets, so many past breast cancer findings only accurately reflect what happens to white women,” Haricharan says. “We hope our research will highlight the need to more closely study cancer in different racial and ethnic groups 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 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 prevent them from repairing DNA, which can make these cells resistant to treatment.
“We have already seen how defects in DNA repair lead to resistance to treatment in breast cancer. But until now, there were no studies to measure how much this differs in black women compared to white women or what explains this difference,” says Haricharan.
To fill this gap, the researchers examined both healthy and tumor tissue from 185 black women and compared them to samples from white women. They found that eight genes fueling DNA repair are expressed differently in black women. They also found consistent molecular differences in cellular signals controlling cell growth rate.
Notably, these differences were not limited to cancer cells — even healthy tissue showed a different gene expression pattern in black women compared to white women.
“It’s so important because if 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 will also be different.” , adds Haricharan.
Towards 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 early treatment with CDK inhibitors, a class of drugs that help prevent 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 should only be used after seeing progress in standard hormone therapy, which means that for some women, at 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 could benefit from earlier treatment. with CDK inhibitors.
“It’s something we can act on immediately, because helping these women is less about finding a new drug and more about changing the schedule of treatments we already have,” says Haricharan.
In a broader sense, the study highlights the critical need for more inclusive biomedical research that understands and respects the need to represent each patient’s unique biology when building datasets and formulating research. hypotheses to be tested in the laboratory.
“The more we look for differences between groups, the more we’re going to find,” says Haricharan. “We need to build better datasets so that we can stop viewing what we observe in white people as the default of all biology, which creates fundamental inequality in biomedical progress.”
Other study authors include Aloran Mazumder, Ph.D., and Athena Jimenez, BA, Sanford Burnham Prebys Medical Discovery Institute; Rachel E. Ellsworth, Ph.D., Henry M. Jackson Foundation for Advancing Military Medicine; Stephen J. Freedland, Ph.D., MD, 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 leading independent biomedical research institute dedicated to understanding human biology and disease and advancing scientific discovery to have a profound impact on human health. For more than 40 years, our research has produced breakthroughs in cancer, neuroscience, immunology, and childhood disease, and is rooted in our NCI-designated Cancer Center and our advanced drug discovery. For more information, visit us at SBPdiscovery.org or on Facebook facebook.com/SBPdiscovery and on Twitter@SBPdiscovery.
Therapeutic advances in medical oncology
Human tissue samples
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The landscape of DNA damage repair in black women with breast cancer
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