I am a molecular oncologist with experience in chromatin control of transcription in cancer. I pioneered studies of the BET bromodomains proteins, a family comprised of BRD2 (originally named RING3), BRD3 and BRD4 in somatic cells, which are important as transcriptional co-regulators. I was the first to report a function for a BET protein, and to link these co-regulators to human cancer. The BET protein field has grown from sixteen papers, when I first published my work, to over 1,300 to date; they have since been implicated in several cancer types. Our recent data have established that BET bromodomain proteins provide a functional link between abnormal metabolism, inflammation and breast cancer progression in post-menopausal African American women. We are now realizing that BET proteins regulate cytokine/chemokine production in the immune cells that infiltrate the breast cancer microenvironment, which are important for immune exhaustion, chemoresistance and metastasis.

More detailed study of these pathways, in African American women in particular, is essential. Risks for breast cancer incidence and progression are not distributed evenly in the population, and are likely stratified by abnormal metabolism such as is found in Type 2 diabetes; yet, the current standard of care in breast oncology does not fully consider the role of diabetes and obesity-associated inflammation as drivers of progression and metastasis. African American women bear a disproportionate burden of poor-prognosis triple negative breast cancer, as well as higher prevalence of obesity, obesity-driven Type 2 diabetes and chronic inflammation, compared to white women. Deeper mechanistic and clinical studies must focus on these more vulnerable patients.

Molecular models and population studies also now suggest that metabolic disease and its associated imbalances in cytokines are more important for breast cancer initiation and progression than obesity per se. My intensive involvement over the last eight years with collaborators in population science, immunology, endocrinology and molecular oncology have prompted me to investigate a new area of high public health significance: breast cancer in non-obese women with metabolic disease and chronic inflammation. New thinking must consider drivers of metastasis, and the role the BET bromodomain proteins play in regulating metastasis potential. We hypothesize the BET proteins are equally important for breast cancer progression in lean women with metabolic disease and its associated chronic inflammation.