Throughout the world, breast cancer is the most frequently diagnosed cancer type among women and is the leading cause of death related to cancer. Interestingly, West African nations have a higher incidence of breast cancer than East African nations. Compared with women of European ancestry, women of African ancestry have higher breast cancer incidence and mortality. Although there are trends in the literature identifying the racial disparity in breast cancer outcomes, many articles attribute this disparity to socioeconomic contexts.
More specifically, triple-negative breast cancer (TNBC), one of the worst breast cancer subtypes has poor survival outcomes attributed to tumor aggression and limited targeted therapy. Due to the high incidence rate of TNBC in individuals with African ancestry, one group led by Dr. Melissa Davis at Morehouse College, set out to determine the molecular difference in women of African ancestry compared to women of European ancestry.
A Cancer Discovery paper by Davis and colleagues first characterized the ancestry profiles of patients in a cohort from the International Center for the Study of Breast Cancer Subtypes (ICSBCS). The team found a mixture of ancestry profiles but noticed many African Americans (AA) with African ancestry from the West African nations. To further isolate this phenomenon, Davis and colleagues looked at gene expression profiles from these patients to determine specific immune signatures.
Davis and colleagues demonstrate differential gene expression in TNBC patients of African ancestry. After a gene-by-gene linear regression analysis, it was reported that related TNBC genes upregulated in patients with African ancestry were downregulated in European ancestry. Therefore, women of African ancestry were more susceptible to get TNBC, which lead to higher mortality rate.
Interestingly, when the highly expressed genes were analyzed further, they found that the pathways associated with chronic inflammation, metastasis, and immune cell trafficking were also upregulated.
Through computational analysis, it was found that estimated immune populations were higher in patients with African ancestry compared to European ancestry. These immune populations included B cells, T cells, and mast cells, which are critical for a beneficial immune response. Although patients with African ancestry have an increased number of immune cells, there are still high TNBC incidence and mortality rates within the African ancestry population. Therefore, Davis and colleagues took a closer look at the immune cell subtypes and found many expressed suppressive markers which prevented the cells from targeting the tumor. The suppressive immune cells around the tumor or in the tumor microenvironment (TME) put patients with African ancestry at a clinical disadvantage.
Davis and colleagues have, for the first time, established a gene expression associated with immune suppression in patients with West African ancestry. The data reported will transform how physicians treat patients. The study clearly states that genetic expression is associated with ancestry, which will dictate cancer treatment in the future. Now that we have the tools to determine our heritage through different companies and services, it may become necessary to talk with a primary care physician about your ancestry and the risks it might pose.
Paper, Melissa Davis, Cancer Discovery, ICSBCS, Morehouse College
