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 into why some women develop more aggressive breast tumors so that personalized prevention and treatment can be designed.

Progress Thus Far

In earlier work, Drs. Ambrosone and Hong found systemic differences in immune profiles in healthy women related to a variant in the DARC gene, which evolved in African populations to protect against malaria infection. They discovered that circulating levels of immune cells are determined by DARC variants and that specific DARC variants are also linked to lower levels of immune cells in tumors. The team then assessed DARC expression and levels in a study of more than 40,000 Black women to see if this variant was associated with risk of aggressive, ER-negative breast cancer. To be able perform comparable analyses in both Black women and white women, Drs. Ambrosone and Hong initiated the New York Breast Cancer Study, enrolling women from across the state. This was expanded to Louisiana in the last year. In related work, the team completed a study showing the important role of DNA methylation—a non-inheritable DNA modification that regulates gene expression—as the link to an observed increased risk of aggressive breast cancer in women who do not breastfeed. Ultimately, the team seeks to answer questions about how these more aggressive tumors develop and to pave the way for better approaches for prevention.

What’s next

In the upcoming year, Drs. Ambrosone and Hong will begin to merge all the molecular data they have collected from tumor tissue analyses from women in their breast cancer studies. They will first look at how physical activity affects changes in tumor and immune cells, followed by other modifiable lifestyle factors. The team will also use new approaches to measure immune cell types in tumors for future studies relating an individual’s immune cells to breast cancer subtype, self-reported race, and modifiable lifestyle factors.

Read more about Dr. Ambrosone’s work as part of BCRF’s Health Equity Initiative here.