Women are most likely to develop estrogen receptor-positive breast cancer, and most cases occur after menopause. Despite ovarian biosynthesis of estrogens having ceased, the adipose tissue continues to produce estrogens locally after menopause and this is thought to drive the growth of breast tumors. Importantly, estrogen levels are dictated by the expression of the aromatase enzyme which is increased after menopause and with obesity. Our group has characterized many of the signaling pathways involved in regulating aromatase in the breast adipose and how these are responsive to changes in inflammatory mediators and adipokines found in dysfunctional adipose tissue. Through these studies, we have identified potential new strategies for intervention, including use of the anti-diabetic metformin or the unacylated form of the appetite-stimulating hormone ghrelin. More recently, our attention has been focused on how dysfunctional adipose tissue may influence breast cancer risk in women already at high risk due to germline mutations in either BRCA1 or BRCA2. We discovered that high BMI and hyperinsulinemia are associated with damage to the DNA of the breast glands in these women – DNA damage being associated with tumorigenesis and breast glands being the site of cancer formation. Our studies revealed that many factors in dysfunctional breast adipose tissue, including estrogens, may be responsible.
Kristy A. Brown, PhD is Associate Professor of Metabolism and Cancer in the Department of Cell Biology and Physiology at the University of Kansas Medical Center, and Co-Program Leader, Cancer Prevention and Control, at the University of Kansas Cancer Center. Dr. Brown obtained her PhD at the Université de Montréal in Canada in 2006 where her thesis focused on understanding the regulation of hormones during the ovulatory process. During her postdoctoral fellowship, her research was aimed at understanding the molecular link between obesity and breast cancer via the regulation of steroid hormone production by metabolic pathways in the breast fat. In 2011, she was appointed co-Head of the metabolism and cancer laboratory at Prince Henry’s Institute, and in 2014, Research Group Head at the Hudson Institute of Medical Research. She was recruited to Weill Cornell Medicine in 2017 and prior to joining the University of Kansas Medical Center, was Associate Professor of Biochemistry in Medicine and the Emilie Lippmann and Janice Jacobs McCarthy Research Scholar in Breast Cancer at Weill Cornell Medicine. Internationally renowned for her work underpinning the molecular relationship between obesity and breast cancer, her team has made seminal contributions to our understanding of aromatase regulation in the breast, the role of obesity-associated factors in driving cancer development and progression, and more recently, the impact of poor metabolic health on cancer risk in women with genetic predispositions to cancer. Dr. Brown has received funding from the NHMRC, the NBCF and the NIH/NCI.