Full Research Project 3

Partnership for the Advancement of Cancer Research Project

Full Research Project 3

Advanced understanding of hormonal contributors to breast cancer etiology and progression

Co-Principal Investigators:

Chris Li, Ph.D. Full Member, Public Health Sciences - Fred Hutch
Peggy Porter, Ph.D. Full Member, Human Biology - Fred Hutch
Ryan Ashley, Ph.D. Assistant Professor, Department of Animal and Range Sciences - NMSU

    The overarching purpose of this project is to advance understanding of the influence of novel membrane-associated steroid receptors on multiple phases of breast cancer progression. Progesterone is a key regulator of the membrane-associated steroid receptors and the importance of progesterone with respect to breast cancer etiology is highlighted by data from the Women's Health Initiative (WHI) randomized trials indicating that while use of combined estrogen and progestin menopausal hormone therapy (CHT) increases risk of breast cancer, use of estrogen alone does not. Dr. Li and his colleagues led the first of many subsequent studies to document that the risk of breast cancer associated with exogenous progestin use is primarily restricted to a more substantial increase in the risk of breast cancers of a lobular histologic type. However, the biological mechanisms underlying the strong relationship between progestin use and lobular breast cancer risk are essentially unknown.

    The findings from our population-based breast cancer studies and from in vitro studies in Dr. Ashley's laboratory identifying the presence and importance of the membrane progesterone receptors and the chemokine and its receptor, CXCR4, in hormone-regulated reproductive pathways, lead us to hypothesize that both membrane-associated receptors and metastatic chemoattractants (such as hormone-regulated CXCL12 and CXCR4) contribute to the differential impact of CHT use on risks and biology of lobular vs. ductal breast cancer.

    We plan to evaluate the contribution of membrane progesterone and estrogen receptor expression and downstream effects in relation to CHT use and histological subtype in well characterized ILC and IDC tumors from a  large ongoing population-based study. Whole genome gene expression will be assessed in a subset of the ILC and IDC tumors to identify and characterize new factors and pathways relevant to the relationship between progesterone and breast cancer. This study will provide vital information relevant to breast cancer etiology and could lead to the identification of novel prevention and therapeutic targets. 

For More Information:

Learn more about the research taking place in Dr. Li's lab here.

Learn more about the research taking place in Dr. Porter's lab here.

Information about Dr. Ryan Ashley's research can be found here.