title: Ulipristal acetate does not impact human normal breast tissue.
abstract: BACKGROUND
  Antiprogestins are of growing interest for the development of new treatments in the gynecological field. Ulipristal acetate (UPA) is a progesterone receptor (PR) modulator considered for long-term administration in contraception and is currently being registered for the treatment of uterine fibroids. In light of the influences of hormonal dysfunction in breast pathologies, the secondary consequences of chronic UPA therapy need to be established. The aim of this study was to determine UPA actions mediated by PR and glucocorticoid receptor (GR) in normal and transformed breast.
  
  
  METHODS
  UPA, progesterone (P) and dexamethasone (DEX) effects were observed on PR and GR responsive genes and on proliferation and apoptosis of normal human breast epithelial (HBE) and breast cancer cells. Human normal breast tissue samples were xenografted in athymic mice and treated with estradiol (E2), or E2 + P, or E2 + P + UPA.
  
  
  RESULTS
  Analysis of PR and GR reporter gene transactivation and their respective endogenous target genes indicated that UPA exerted anti-progestational and anti-glucocorticoid activity in both types of cells with a more pronounced effect in cancer cells. When combined with P or DEX, UPA limits the proliferation of HBE cells but increases growth in breast cancer cell lines. UPA administration had no impact on the mitotic index on xenografted human breast tissue exposed to gonadal hormones at similar concentrations to those present in normal women.
  
  
  CONCLUSIONS
  Although further clinical trials are required to confirm that the results from our experimental models can be extrapolated to women treated with UPA, they suggest that such treatment would not be deleterious to normal breast tissue at least for a cycle (28 days) of continuous administration.
authors: INSERM-UPMC, UMRS 938, Hôpital Saint-Antoine, 75012 Parris,  France.
authors: Laudine
authors: L
authors: Communal
authors: Myriam
authors: M
authors: Vilasco
authors: Justine
authors: J
authors: Hugon-Rodin
authors: Aurélie
authors: A
authors: Courtin
authors: Najat
authors: N
authors: Mourra
authors: Najiba
authors: N
authors: Lahlou
authors: Sylvie
authors: S
authors: Dumont
authors: Marc
authors: M
authors: Chaouat
authors: Patricia
authors: P
authors: Forgez
authors: Anne
authors: A
authors: Gompel
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D001940:Breast / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D003270:Contraceptive Agents / Q000494:pharmacology*; D019925:Cyclin A / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects; D004958:Estradiol / Q000378:metabolism; D054890:Fatty Acid Synthase, Type I / Q000096:biosynthesis; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis; D007889:Leiomyoma / Q000378:metabolism; D042361:Mammary Glands, Human / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009649:Norpregnadienes / Q000494:pharmacology*; D011374:Progesterone / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D015533:Transcriptional Activation; D014183:Transplantation, Heterologous
chemical_list: D051017:Apoptosis Regulatory Proteins; D003270:Contraceptive Agents; D019925:Cyclin A; C099815:IER3 protein, human; D019394:Ki-67 Antigen; D008565:Membrane Proteins; D009649:Norpregnadienes; D019253:Proto-Oncogene Proteins c-bcl-2; D011965:Receptors, Glucocorticoid; D011374:Progesterone; D004958:Estradiol; D003907:Dexamethasone; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I; C555622:ulipristal acetate