Christine B. Ambrosone, PhD

Understanding the molecular drivers of aggressive breast cancer in Black women and how these are different in white women.

Impact

Black women are 42 percent more likely to die of their breast cancer than white women. Those diagnosed with breast cancer are more likely to be younger than newly diagnosed white women and are two times more likely to be diagnosed with triple-negative breast cancer (TNBC), an aggressive subtype of the disease. Drs. Ambrosone and Hong are investigating several biological and lifestyle factors that may influence the incidence of TNBC in Black women. This work may provide new insights at the population level into why some women develop more aggressive breast tumors so that personalized prevention and treatment can be designed.

Progress Thus Far

The team is studying immune cells that are in and around breast tumors, and how these types of immune cells differ between more aggressive and less aggressive tumor subtypes and between Black women and white women. They showed that some tumors appear to have a strong immune response, but the cells are actually ‘exhausted’ and dysfunctional. These findings led to a large national study to see if patients with exhausted immune cells, particularly Black women, could benefit from immunotherapy, which can re-invigorate these exhausted cells. Drs. Ambrosone and Hong also found systemic differences in immune profiles in healthy women related to a variant in the DARC gene, which evolved in African populations and stimulates a strong immune response to fight malaria infection. They discovered that circulating levels of immune cells are determined by DARC genotypes and in the past year, showed that DARC genotypes are also linked to immune cells in tumors. Work is ongoing to investigate whether DARC genotypes are also associated with more aggressive breast cancer subtypes. and we are studying how the immune system can make tumors behave more aggressively.

What’s next

In the coming year, Drs. Ambrosone and Hong will more deeply explore how DARC genotypes may be related to breast tumor aggressiveness. The team will also look at how immune processes within tumors as well as inherited differences in immune response may influence racial disparities in tumor aggressiveness as well as outcomes.

If not for BCRF, we would not have had the freedom to explore exciting new ideas, some which may be ‘outside of the box’ that we don’t yet have preliminary data for and make important discoveries about the causes of aggressive breast cancer.