{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"American Association for Cancer Research"}],"indexed":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T13:13:17Z","timestamp":1764076397899,"version":"3.45.0"},"posted":{"date-parts":[[2025,11,25]]},"reference-count":0,"publisher":"American Association for Cancer Research (AACR)","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<div>AbstractPurpose:<p>Preclinical data suggest that antiprogestins inhibit the growth of luminal breast carcinomas that express higher levels of progesterone receptor isoform A (PRA) than isoform B (PRB). Thus, we designed a presurgical window of opportunity trial to determine the therapeutic effects of mifepristone in patients with breast cancer, based on their high PRA\/PRB isoform ratio (MIPRA; NCT02651844).<\/p>Patients and Methods:<p>Twenty patients with luminal breast carcinomas with PRA\/PRB > 1.5 (determined by Western blots), and PR \u2265 50%, na\u00efve from previous treatment, were included for mifepristone treatment (200 mg\/day orally; 14 days). Core needle biopsies and surgical samples were formalin fixed for IHC studies, while others were snap-frozen to perform RNA sequencing (RNA-seq), proteomics, and\/or Western blot studies. Plasma mifepristone levels were determined using mass spectrometry. The primary endpoint was the comparison of Ki67 expression pretreatment and posttreatment.<\/p>Results:<p>A 49.62% decrease in Ki67 staining was observed in all surgical specimens compared with baseline (<i>P<\/i> = 0.0003). Using the prespecified response parameter (30% relative reduction), we identified 14 of 20 responders. Mifepristone induced an increase in tumor-infiltrating lymphocytes; a decrease in hormone receptor and pSer118ER expression; and an increase in calregulin, p21, p15, and activated caspase 3 expression. RNA-seq and proteomic studies identified downregulated pathways related to cell proliferation and upregulated pathways related to immune bioprocesses and extracellular matrix remodeling.<\/p>Conclusions:<p>Our results support the use of mifepristone in patients with luminal breast cancer with high PRA\/PRB ratios. The combined effects of mifepristone and estrogen receptor modulators warrant clinical evaluation to improve endocrine treatment responsiveness in these patients.<\/p><p><i><a href=\"https:\/\/aacrjournals.org\/clincancerres\/article\/doi\/10.1158\/1078-0432.CCR-22-3374\" target=\"_blank\">See related commentary by Ronchi and Brisken, p. 833<\/a><\/i><\/p><\/div><\/jats:p>","DOI":"10.1158\/1078-0432.c.6533123","type":"posted-content","created":{"date-parts":[[2023,4,1]],"date-time":"2023-04-01T00:57:05Z","timestamp":1680310625000},"source":"Crossref","is-referenced-by-count":0,"title":["Data from Beneficial Effects of Mifepristone Treatment in Patients with Breast Cancer Selected by the Progesterone Receptor Isoform Ratio: Results from the MIPRA Trial"],"prefix":"10.1158","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0766-3838","authenticated-orcid":false,"given":"Andr\u00e9s","family":"El\u00eda","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2356-5576","authenticated-orcid":false,"given":"Leo","family":"Saldain","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0486-9526","authenticated-orcid":false,"given":"Silvia I.","family":"Vanzulli","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8237-2390","authenticated-orcid":false,"given":"Luisa A.","family":"Helguero","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0392-7552","authenticated-orcid":false,"given":"Caroline A.","family":"Lamb","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5995-371X","authenticated-orcid":false,"given":"Victoria","family":"Fabris","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8398-6271","authenticated-orcid":false,"given":"Gabriela","family":"Pataccini","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0033-0179","authenticated-orcid":false,"given":"Paula","family":"Mart\u00ednez-Vazquez","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1253-4037","authenticated-orcid":false,"given":"Javier","family":"Burruchaga","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5916-6310","authenticated-orcid":false,"given":"Ines","family":"Caillet-Bois","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7819-2714","authenticated-orcid":false,"given":"Eunice","family":"Spengler","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1123-3120","authenticated-orcid":false,"given":"Gabriela","family":"Acosta Haab","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1980-8937","authenticated-orcid":false,"given":"Marcos","family":"Liguori","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2686-6326","authenticated-orcid":false,"given":"Alejandra","family":"Castets","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5771-7112","authenticated-orcid":false,"given":"Silvia","family":"Lovisi","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9044-2149","authenticated-orcid":false,"given":"Mar\u00eda F.","family":"Abascal","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9917-4953","authenticated-orcid":false,"given":"Virginia","family":"Novaro","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1353-156X","authenticated-orcid":false,"given":"Jana","family":"S\u00e1nchez","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3288-3496","authenticated-orcid":false,"given":"Javier","family":"Mu\u00f1oz","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8412-3010","authenticated-orcid":false,"given":"Jos\u00e9 M.","family":"Beliz\u00e1n","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9206-2369","authenticated-orcid":false,"given":"Mart\u00edn C.","family":"Abba","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9009-7501","authenticated-orcid":false,"given":"Hugo","family":"Gass","sequence":"first","affiliation":[]},{"given":"Paola","family":"Rojas","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0555-2309","authenticated-orcid":false,"given":"Claudia","family":"Lanari","sequence":"first","affiliation":[]}],"member":"1086","container-title":[],"original-title":[],"deposited":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T13:09:43Z","timestamp":1764076183000},"score":1,"resource":{"primary":{"URL":"https:\/\/aacr.figshare.com\/collections\/Data_from_Beneficial_Effects_of_Mifepristone_Treatment_in_Patients_with_Breast_Cancer_Selected_by_the_Progesterone_Receptor_Isoform_Ratio_Results_from_the_MIPRA_Trial\/6533123\/2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,25]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1158\/1078-0432.c.6533123","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1158\/1078-0432.CCR-22-2060","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2025,11,25]]},"subtype":"other"}}