Research shows that before 1985, breast cancer mortality rates were similar for Black and white women. But as screening and treatment advances became available, Black women fell behind, leading to a disparity gap that still persists today. The fact that Black women are 40 percent more likely to die from breast cancer clearly illustrates that advances in breast cancer research and treatments are not reaching all populations equally. But limited access to breast cancer care is not singularly responsible for the disparity.
BCRF researchers and others are focused on the multi-factorial reasons for disparities, and this was apparent at this year’s American Association of Cancer Research (AACR) annual meeting—one of the largest cancer research conferences. Educational sessions helped bring attendees up to speed, researchers shared key findings, and in-depth discussion panels covered strategies for advancing disparities research, all with the goal of reaching and benefitting more patients.
Here are just a few of the many topics discussed during this year’s AACR meeting.
Triple-negative breast cancer (TNBC) is an aggressive subtype of the disease that can be challenging to treat as it lacks the three main drivers of breast cancer: estrogen and progesterone receptors (ER and PR) and HER2 protein. This form disproportionately affects young Black women. We know that TNBC is actually a group of diseases, and researchers are steadily working to gain a better understanding of its complexities to develop more effective therapies. At AACR, Dr. Clayton Yates of Johns Hopkins University gave a sweeping presentation on his research and what we currently know.
Key among the findings is that approximately 70 percent of TNBCs in Black women can be categorized as quadruple-negative breast cancer (QNBC). These lack ER, PR, and HER2, along with androgen receptors (ARs).
ARs are known to drive prostate cancer growth. Despite having been identified in breast cancer many years ago, researchers are still focused on gaining a full understanding of its role in breast cancer. Since TNBC has limited treatment options, researchers have been exploring AR as a viable target. While this may be an option for some TNBCs, the characteristics of QNBC indicates that targeting AR may not be an option for all TNBCs. TNBC’s aggressive nature is well-reported, but as Dr. Yates and others have shown, QNBC is particularly aggressive.
More investigation is needed to understand ARs’ innerworkings to identify any vulnerabilities and devise novel strategies to treat these aggressive breast cancers.
BCRF investigators and Health Equity Initiative members Drs. Lisa Newman and Melissa Davis have been on the cutting-edge of research uncovering the role that genetics and biology play when it comes to Black women’s risk of breast cancer—what they’ve come to call “oncologic anthropology” examining variations in cancer incidence and outcomes among people of different races and ethnicities.
At AACR, Dr. Newman and others discussed key players that have emerged from research in oncologic anthropology, as well as genetic- and tumor-related factors that are expressed differentially in Black women. Two genes—Kaiso and DARC—have been linked to highly aggressive TNBC tumors and found to be dysregulated in TNBC tumors from Black women compared to their white counterparts.
Kaiso linked to TNBC’s aggressiveness, metastasis, and poor survival
Kaiso is an ancestral marker discovered in West African women and their descendants in the U.S.Studies have also showed elevated Kaiso levels in TNBC tissues from Black women compared to their white counterparts. This led investigators including Drs. Davis, Newman, and Yates to delve into Kaiso’s role. In his AACR presentation, Dr. Yates described his studies looking at how Kaiso influences cell-to-cell adhesion which, when inhibited, may promote cell detachment and metastasis. Kaiso’s ability to increase specific immune cells in the tumor microenvironment—called macrophages—may explain some of the differences in how Black women’s immune system functions compared to white women.
DARC gene may explain poor breast cancer outcomes in Black women
The DARC gene (Atypical Chemokine Receptor 1 gene, ACKR1/DARC) has several distinct variants in virtually all West Africans and in about 70 percent of African Americans. The DARC gene has been shown to protect against malaria. However, this advantage for a population that resides in an area where malaria is prevalent has consequences in the context of breast cancer. Inflammation can make cancers grow faster. DARC keeps inflammation in check and without it, inflammation increases. Black women with a DARC variant may have lower levels of DARC on their red blood cells and, while that protects against malaria, it means they don’t have DARC’s anti-inflammatory advantage when it comes to cancer. This may partly explain why Black women’s breast cancers are more aggressive.
Others have shown that the DARC receptor normally regulates levels of a family of proteins called chemokines that keep inflammation at bay. Drs. Davis and Newman and their colleagues examined DARC levels in breast tumor tissue and found that tumors from Black women, on average, had lower DARC levels. Those lower levels were associated with more aggressive tumors while higher levels were strongly associated with longer survival times after breast cancer diagnosis.
Black women have differences in other factors involved in an immune response. And while breast tumors from Black women show the presence of cancer fighting T-cells, they are more likely to be deactivated and thus unable to launch an effective immune response to the tumor.
The tumor microenvironment’s role in cancer disparities
Immune cells are one of several factors in the environment surrounding a tumor. At AACR, Dr. Davis led a session detailing the differences in tumor biology and the composition of the tumor microenvironment (TME) in Black versus white women—findings that may help improve our understanding of breast cancer progression. Termed spatial omics, this process involves looking at the types of cells in and around the tumor, their proximity to the tumor, how they are spatially located in relation to each other, and how they differ across compartments of the tumor.
Using spatial omics, she and others including fellow BCRF investigator Dr. Christine Ambrosone, have observed several differences between Black women and white women:
Studies are ongoing to delve into these findings to determine how changes in immune cells and their localization in the TME can inform treatment decisions, improve outcomes, and close disparities.
Social determinants of health (SDoH) are conditions in which people are born, grow, work, live, and age that affect health outcomes. Combined with structural determinants of health—the forces and systems shaping the conditions of daily life, such as structural racism and persistent poverty—they form a complex web of factors, built over generations, that impact health inequities beyond a person’s access to care.
BCRF investigator Dr. Scarlett Gomez along with fellow BCRF investigator Dr. Samilia Obeng-Gyasi and Dr. Lauren McCollough of Emory University discussed the importance of unraveling these intertwined factors to truly decrease disparities. This includes awareness of how structural racism and the legacies of historical segregation are deeply embedded in people’s neighborhoods—neighborhoods that today have limited access to healthy food and regular healthcare. Their discussion focused on how these factors really contribute to breast cancer outcomes, highlighting the ZNA (zip code DNA) index as an example.
Research has shown that neighborhood deprivation correlates with breast cancer mortality. In fact, low neighborhood socioeconomic status drives survival disadvantage and could explain about seven percent of breast cancer cases. The ZNA index accounts for a person’s poverty level, income, occupation, housing, employment, and education. As these researchers discussed at AACR, by using ZNA, they hope to gain a better understanding of how where one lives influences one’s health to ultimately devise interventions.
Read more about how BCRF is tackling disparities Black women and people of color face in breast cancer.
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