Avon Funds Study of Aggressive Breast Cancer

Xiaojiang Cui, PhD, a research scientist in the Women's Cancer Program at the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute and the Department of Surgery, has received a two-year, $300,000 grant from the Avon Foundation to investigate the role of the protein FOXC1 in the development of aggressive breast cancer.

Xiaojiang Cui, PhD

Cui's study will focus on breast cancers arising from mutations in the BRCA1 gene. Such cancers commonly are triple-negative — so called because they lack three known breast cancer markers. While treatable with chemotherapy, these cancers are associated with a poor clinical outcome and may return shortly after remission. Thus, more effective therapy is urgently needed, Cui said.

Although extensive effort has gone into understanding the role of BRCA genes, it is still unclear why BRCA1 is associated with triple-negative breast cancer. Cui said he believes FOXC1 may help explain this association.

"We have previously found that FOXC1 is a critical biomarker for triple-negative breast cancer. Therefore, we hypothesize that FOXC1 mediates the biological effects of BRCA1 mutations and plays a critical role in the development of this form of the disease," said Cui, associate professor of surgery and principal investigator on the study.

To test his hypothesis, Cui and his Cedars-Sinai colleagues plan to alter FOXC1 protein levels in various in vitro models of BRCA1-mutant human breast cancer cells. 

By measuring the concentration of proteins, the researchers plan to determine whether the FOXC1 protein is produced specifically, or exclusively, in triple-negative BRCA1-mutant breast tumors and whether its levels predict the clinical outcome of those cancers. They will also test the level of FOXC1 in normal breast tissues from BRCA1 mutation carriers undergoing prophylactic mastectomies and aim to establish FOXC1 as a marker for improving the estimates of breast cancer risk for such individuals.

"Our study will provide insight into biological mechanisms of triple negative BRCA1-mutant breast cancer development," said Cui. He said the research may potentially have implications for the treatment and prevention of this type of cancer.

Cui's collaborators include: Armando E. Giuliano, MD, executive vice chair of the Department of Surgery for surgical oncology and a professor of surgery; Farin Amersi, MD, assistant professor of surgery; Farnaz Dadmanesh, MD, co-director of Pathology Outreach at the Samuel Oschin Comprehensive Cancer Institute; and Beth Karlan, MD, director of the Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute and professor of obstetrics and gynecology.