iNOVA4Health Seminar

Title: Hormones and breast cancer: how models matter

Speaker: Cathrin Brisken, MD, PhD

Affiliation: ISREC, School of Life Sciences, Ecole Polytechnique Fédérale (EPFL) http://brisken-lab.epfl.ch/ | Co-Director, International Cancer Prevention Institute http://www.icpi-web.org

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.