Thomas E Bartlett, Iona Evans, Allison Jones, James E Barrett, Shaun Haran, Daniel Reisel, Kiriaki Papaikonomou, Louise Jones, Chiara Herzog, Nora Pashayan, Bruno M Simões, Robert B Clarke, D Gareth Evans, Talayeh S Ghezelayagh, Sakthivignesh Ponandai-Srinivasan, Nageswara R Boggavarapu, Parameswaran G Lalitkumar, Sacha J Howell, Rosa Ana Risques, Angelique Flöter Rådestad, Louis Dubeau, Kristina Gemzell-Danielsson, Martin Widschwendter
BACKGROUND: Breast cancer is a leading cause of death in premenopausal women. Progesterone drives expansion of luminal progenitor cells, leading to the development of poor-prognostic breast cancers. However, it is not known if antagonising progesterone can prevent breast cancers in humans. We suggest that targeting progesterone signalling could be a means of reducing features which are known to promote breast cancer formation. METHODS: In healthy premenopausal women with and without a BRCA mutation we studied (i) estrogen and progesterone levels in saliva over an entire menstrual cycle (n = 20); (ii) cancer-free normal breast-tissue from a control population who had no family or personal history of breast cancer and equivalently from BRCA1/2 mutation carriers (n = 28); triple negative breast cancer (TNBC) biopsies and healthy breast tissue taken from sites surrounding the TNBC in the same individuals (n = 14); and biopsies of ER+ve/PR+ve stage T1-T2 cancers and healthy breast tissue taken from sites surrounding the cancer in the same individuals (n = 31); and (iii) DNA methylation and DNA mutations in normal breast tissue (before and after treatment) from clinical trials that assessed the potential preventative effects of vitamins and antiprogestins (mifepristone and ulipristal acetate; n = 44)...
June 15, 2022: Genome Medicine