Black women diagnosed with hormone receptor positive (HR+) breast cancer experience significantly worse outcomes than white women.
With HR+ representing the most common type of breast cancer and a leading cause of cancer-related death in women around the world, Svasti Haricharan’s lab set out to uncover more about why this gap exists and how it can be closed.
Research has shown that genetics plays a large role in health disparities for a range of diseases and conditions. With this hypothesis in mind, Haricharan and her team searched for a dataset to examine the specific race or ancestry-based molecular biology that may lead to poorer HR+ breast cancer outcomes in Black women.
“Most existing datasets heavily underrepresent anyone who is non-white, so we went to the Department of Veterans Affairs, which has the largest archival tissue bank from non-white women,” Haricharan said.
When her team took a close look at the HR+ breast cancer cells in Black and white women, the results were not what they were expecting.
“What stood out immediately was that we weren't seeing that many differences in what was happening inside the cancer cells, but we were seeing differences in what was happening outside the cells,” Haricharan said.
Often, disparities can be explained by differences within the cancer cells, such as genetic mutations that are associated with ancestry. But differences outside the cells, like those the team found, are caused by lifestyle factors.
“The findings didn't actually seem to match with ancestry, but more with lifestyle factors and social determinants,” Haricharan said. “It was not necessarily based on how much of a certain ancestry you had, but more the burdens you might face because of that identity, the cultural milieu in which you were growing up or the life challenges you were facing, which are so often in this world associated with structural determinants, because of racism and other structural factors.”
The differences mainly appeared in the women’s collagen, which is like glue that cells cling to as they grow in tissues throughout the body.
“The collagen architecture was very different in Black women compared to white women,” Haricharan said. “If Black women didn't have that collagen patterning, cancer cells could not metastasize. Weirdly, cells from white women didn't have that same requirement. In fact, when we put cells from white women into the same collagen architecture that we see in Black women's breasts, the cells stopped metastasizing.”
Similar differences in collagen architecture have been shown for other types of cancers but her team now demonstrated them with HR+ breast cancer.
Haricharan’s team also noticed that the immune response process — which requires immune cells to break through collagen to attack cancer cells — was different in Black and white women.
“Black women's tumors had way more immune cells but they were not good at killing cancer cells, whereas in white women's tumors, there were far fewer immune cells but they were really good at killing cancer cells,” Haricharan said. “Other studies have shown that ancestry dictates the kind of immune response you can raise, but we found out that actually that immune phenotype was linked to poverty burden and not to race.”
Further examination revealed that white women who faced a high poverty burden showed the same issue — many immune cells that were not able to kill cancer cells — proving that the issue is linked to socioeconomic conditions.
“Because Black women in the U.S. and in many parts of the world are more likely to live in high poverty areas or face high poverty burden, there's been this misunderstanding of the data in the cancer research field,” Haricharan said. “We've all thought that this immune phenotype was associated with race and ancestry, but it looks like it is only aligned with poverty burden, maybe because of chronic stress.”
Haricharan focused on disparities in HR+ breast cancer because this subtype is often overlooked in the research field, despite being the most common type of breast cancer Black women are diagnosed with. She hopes this study encourages the broader research community to adopt a more holistic view, examining factors outside of the cell, and outside the body, that may impact health.
“Right now, precision oncology is largely based on data from white women, which means it is very precise for white women, but it is not very representative for most other demographics of women,” Haricharan said. “So, the idea that things like poverty burden can affect patient outcome by directly changing the biology of the cancer cell tells us we need to be taking a wider view of how we study these systems, and suggests a path forward for how we could have a better educated, more equitable precision oncology system.”
Haricharan is now expanding on this study in collaboration with UC San Diego using a sample of 7,000 HR+ breast cancer patients of multiple mixed ancestry to see if they notice the same differences in other non-white minority women that they found in Black women.
“Whether you're a scientist or a layperson or a breast cancer survivor, you think of cancer as this unique monster living inside your body,” Haricharan said. “But, really, so much of what a cancer cell is is defined by what's around it and what you're going through in your life. A beacon of hope is that now that we can make these datasets that have better annotations for life experience factors, maybe that is the code to make us one step closer to a cure.”
This study was funded by the American Cancer Society and conducted in collaboration with Texas A&M University, UC San Diego, CSU San Marcos, the Department of Veterans Affairs, and Cedars-Sinai.
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