(1) How do different progesterone-like substances used in birth control pills and hormone replacement therapy change the breast?

HYPOTHESIS

Androgenic and anti-androgenic activities determine the ability of different progestins to induce inflammatory cytokines and cell proliferation in the human breast epithelium.

Background & Significance

Birth control pills and hormone replacement therapies increase breast cancer risk. They contain different types of progesterone-like chemicals, which differ in chemical structure and  hence their ability to interact with the receptor for testosterone. How each individual drug changes human breast cells has been impossible to assess because there were no models to study this. The Brisken Laboratory has developed ex vivo and in vivo models to study the effects of hormones in the human breast epithelium in physiologically relevant conditions. We propose that the ability of different progesterone-like chemicals to induce inflammatory cytokines and cell proliferation in the human breast epithelium is what determines their potential to accelerate cancer development. Determining the biological activities of different progesterone-like chemicals will help to develop more informed choices in hormonal contraception and hormone replacement therapy and ultimately help to prevent breast cancer.

Objectives

Use physiologically relevant ex vivo and in vivo models to study the effects of progestins on the breast epithelium;

Determine how progestins with different androgenic properties affect cell proliferation in the human breast epithelium;

Determine how different progestins affect the expression of inflammatory cytokines;

Test whether pharmacological inhibition of AR signaling abrogates progestin-induced cell proliferation and cytokine induction.

Enrolment in Doctoral degree(s):

  • Swiss Federal Institute of Technology