Breast Cancer - Anti-Progestin Prevention Study 1
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      The primary objective of this study is to determine the effects of the antiprogestin
      ulipristal acetate (UA) on the epithelial and stromal compartments of the normal breast in
      women at increased risk of breast cancer (BC) and to relate these effects to quantitative
      changes on multiparametric magnetic resonance imaging (MRI). The goal is to define predictive
      imaging biomarkers for subsequent testing in randomised prevention trials of antiprogestins.
    

Detailed description: 
      Breast cancer (BC) is the commonest cancer, affecting 1.4 million women per year of whom a
      third die from the disease. There is an urgent need for new approaches to BC prevention.
      Progesterone is a hormone that is produced naturally from a woman's ovaries during each
      menstrual cycle and is often used in hormone replacement therapy (HRT) after the menopause.
      When used in HRT progesterone increases the risk of BC and BC death. In experiments in mice
      and rats progesterone has been shown to increase the growth of the normal mammary gland (the
      rodent breast). When human breast tissue is grown in the laboratory it also grows in response
      to progesterone. In particular progesterone has been shown to increase the growth of
      particular cells called stem cells which survive for a long time in the breast. It is thought
      that the exposure of these stem cells to progesterone over many years is the reason that
      women whose periods start early and finish late or those who do not have a pregnancy to
      interrupt their menstrual cycles and those that take HRT all have an increased risk of BC.

      In this project the investigators will use a drug that blocks the effects of progesterone
      called ulipristal acetate (UA, EsmyaTM) that is currently licenced in the treatment of
      fibroids of the uterus. When used to treat fibroids UA is very well tolerated with no
      increase in side effects compared to a placebo tablet. 30 women at increased risk of BC will
      be recruited and have magnetic resonance imaging (MRI) scan and mammogram followed by a
      biopsy of one breast. After 3 months of UA treatment the MRI will be repeated along with a
      biopsy from the other breast. The effects of UA on many different cell types in the biopsies,
      including the stem cells and also the tissues like collagen that support them will be
      examined in detail. The effects of UA treatment on gene and protein expression in the breast
      tissue will also be examined. The goal is to identify which women will be sensitive or
      resistant to UA as a BC prevention treatment. In addition changes in the MRI scans with UA
      treatment will be examined using several different analysis techniques to try and identify
      who will likely benefit from UA treatment in the future without the need for biopsies.
    

Intervention name(s): ulipristal acetate
Intervention type(s): Drug
Intervention description(s): selective progesterone receptor modulator
Other intervention name(s): Esmya
Intervention MeSH terms: Ulipristal acetate
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention