Molecular differences may explain higher breast cancer mortality rates among Black women
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Black women are 41% more likely to die of breast cancer than white women, according to American Cancer Society statistics.
Research from Sanford Burnham Prebys suggests this disparity may be at least partly driven by molecular differences between the breast cells of Black and white women.
“When we look at ER-positive breast cancer, which is the more treatable form, we see that Black women have about the same incidence rate but worse outcomes, even when you control for access to health care and economic status,” researcher Svasti Haricharan, PhD, assistant professor at Sanford Burnham Prebys, said in an interview with Healio. “So, this struck us as a biology problem as much as it is a societal problem.”
Haricharan and discussed the study’s findings and how they might enable future treatments targeted specifically to the biology of Black women with breast cancer.
Healio: What inspired you to study racial disparities in ER-positive breast cancer?
Haricharan: In terms of disparities, most of the focus has been on triple-negative breast cancer. However, when we looked a little more closely at the data, we realized that although Black women are more likely to get triple-negative breast cancer than white women, their outcomes are the same when you control for socioeconomic status and access to health care. That’s why we started asking, “Are there somatic differences? Are there cells that are forming the cancer and changing their molecular biology in different ways when they grow in Black women than when they grow in white women?”
Healio: How did you conduct your study?
Haricharan: Because Black women are so underrepresented in most cancer data sets, including breast cancer, we couldn’t ask the question we really wanted to ask, which was, what are all the differences in the signaling pathways in tumors of Black women vs. white women? We simply had too few samples from Black women to do that sort of agnostic study. So, we decided to ask a more focused question. Recently, it came out that in about 20% of white women with ER-positive breast cancer, the cancer cells were turning off DNA damage repair proteins. Basically, they were acquiring more damage, and this was making them resistant to the standard treatments that we give to women with ER-positive breast cancer.
When we saw this outcome discrepancy between Black women, our first thought was that maybe breast cancer cells growing in Black women are more easily able to turn off their DNA damage repair pathways. So, we’re ending up with a group of women who, just from their molecular biology, may have cancer cells that are not as responsive to standard therapies as those in white women are and, therefore, have worse outcomes. So, our question was, can we see these DNA damage repair proteins in tumors from Black women being turned off more efficiently?
Healio: What did you find?
Haricharan: We found that 40% to 60% of tumors from Black women had a DNA repair signature that was different from what we saw in white women, and that signature was associated with worse outcomes in multiple independent data sets. We think it’s because the specific DNA repair proteins that are regulated differently in tumors from Black women delink the proliferative potential of the cell from external stimuli, so when the patient is given treatment that would normally tell the cell to stop proliferating, these DNA repair proteins don’t translate that signal to the cell. Therefore, the cell keeps proliferating even in the presence of therapy.
Healio: What are the implications of your findings?
Haricharan: These differences in the molecular biology are clinically actionable. So, we could basically look at the molecular biology and say these women are not going to respond to standard-of-care, but they will respond to other treatments that we’re currently giving them. That was a big deal for us — something we can hang our hats on. We can recognize the differences in molecular biology and work with them and streamline treatment more effectively.
Another implication is that for too long, our researchers in the field have been stuck in two buckets. One bucket is all about socioeconomic status, lifestyle factors and access to health care. Then there’s another bucket that scientists believe involves molecular biology and genes . I think this study is showing us that it’s not an “either/or” situation, because we are also always responding to various external factors, like socioeconomic status, chronic stress from systemic racism, etc. That is part of our biology. It would be quite simplistic to imagine that none of what’s happening out there in the chaotic world is affecting what is going on inside our bodies. So, on a more philosophical level, this is just telling us there aren’t two buckets — there is just one, and we need to do much better about integrating at multiple levels to understand what’s going on in that bucket.
Healio: What’s next in your research on this topic?
Haricharan: One of the things we realized during our study was how difficult it is to find data sets that adequately represent Black women. About halfway through the study, my postdoctoral trainee, Aloran Mazumder, PhD, and I decided we were going to have to build a data set. It was ridiculous — we had data from thousands and thousands of patients with breast cancer, yet we barely had enough on Black women to make a cogent hypothesis. So, the first thing we are doing is collaborating with Veterans Affairs and the Department of Defense to use some archival tissue they have from Black patients with breast cancer who are in the military and build a bigger data set with more virtual information, and we can ask interesting questions about the differences in molecular biology.
We also realized that all the experimental model systems we’re using in the lab are based on the biology of white women. It struck me that it’s very difficult for us to study what treatments are going to be more effective when targeting the tumors of Black, Asian or Hispanic women because we don’t have those model systems. So, we are trying to take what we see in the limited patient data from these groups and modulate the systems, so we’re not just finding what works in white women. One size does not fit all.
Healio: Is there anything else you’d like to mention?
Haricharan: This can be addressed on a very practical level. We can fix this problem today. We’re not talking about pie in the sky. We’re talking about how we can take existing clinical diagnostics and therapeutics and make them work better for everyone, not just for white people.
References:
Cancer facts & figures for African American/Black people. Available at: www.cancer.org/research/cancer-facts-statistics/cancer-facts-figures-for-african-americans.html. Accessed April 1, 2022.
Mazumder A, et al. Ther Adv Med Oncol. 2022;doi:10.1177/17588359221075458.
For more information:
Svasti Haricharan, PhD, can be reached at 10901 North Torrey Pines Road, La Jolla, CA 92037; email: sharicharan@sbpdiscovery.org.
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