INOVA4HEALTH SEMINAR: "Hormones and breast cancer: how models matter"

Cathrin Brisken, MD, PhD

Associate Professor of Life Sciences, Swiss Federal Institute of Technology, Lausanne (EPFL)

Co-Director, International Cancer Prevention Institute

ABSTRACT

Hormones control breast development and function and impinge on breast carcinogenesis. Seventy-five percent of breast cancers are estrogen receptor a positive (ER+) and hormone exposures impact on development and progression of these tumors. Research on these tumors is hampered by lack of adequate in vivo models; cell line xenografts require non-physiological hormone supplements, and patient-derived xenografts (PDXs) are hard to establish. We show that the traditional grafting of ER+ tumor cells into mammary fat pads induces TGFb /SLUG signaling and basal differentiation when they require low SLUG levels to grow in vivo. Grafting into the milk ducts suppresses SLUG; ER+ tumor cells develop, like their clinical counterparts, in the presence of physiological hormone levels. Intraductal ER+ PDXs are retransplantable, predictive, and appear genomically stable. The model provides opportunities for translational research and the study of physiologically relevant hormone action in breast carcinogenesis. 

SHORT BIO

Dr Cathrin Brisken is internationally recognized for her work on endocrine control of mammary gland development and breast carcinogenesis. She received her MD and PhD degree in Biophysics from the Georg August University of Göttingen, and completed her postdoc in cancer biology with Dr R.A. Weinberg at the Whitehead Institute of Biomedical Research in Cambridge. Dr Brisken’s lab focuses on the cellular and molecular underpinnings of estrogen and progesterone receptor signaling in the breast and the respective roles of these hormones and hormonally active compounds in carcinogenesis. The lab has pioneered in vivo approaches to genetically dissect the role of the reproductive hormones in driving mouse mammary gland development and shown how they control intercellular communication. Dr Brisken’s group has developed ex vivo and humanized mouse models using patient samples to study hormone action in human tissues in normal settings and during disease progression.

Host: Catarina Brito