Fabienne Meier-Abt
University Hospital of Basel, Switzerland
Title: Mechanisms of Early Pregnancy-Mediated Breast Cancer Protection
Biography
Biography: Fabienne Meier-Abt
Abstract
Pregnancy at early, but not late age, has a substantial and life-long protective effect againstbreast cancer. The expected overall increase in breast cancer incidence in the coming yearsdemands the development of strategies to mimic early-age pregnancymediated protection.Recently, converging results on molecular and cellular mechanisms underlying the protectiveeffect of early-age pregnancy were reported in rodent models and women. In particular, earlyparity induces differentiation and downregulates the Wnt/Notch signaling ratio and the in vitro and in vivo proliferation potential of basal stem/progenitor cells in mice. These early parityinducedchanges of gene expression and dynamics of mammary stem/progenitor cells werecaused primarily by a decrease in the proportion of hormone-sensitive and Wnt4-secretingluminal epithelial cells. Furthermore, they were of life-long duration and absent upon latepregnancy. Similar findings were made in humans confirming that decreased hormone- andWnt4-mediated Wnt signaling in mammary stem/progenitor cells plays a key role in theprotective effect of early-age pregnancy against breast cancer. However, in addition to decreased Wnt signaling, increased cellular quiescence induced by TGFβ signaling might also be involved in the breast cancer-protective effect of early pregnancy in humans. These congruent andcomplementary findings in mouse and human mammary epithelial stem/progenitor cells provide promising initial targets for translational studies directed toward the development ofpharmacological breast cancer prevention strategies.