| Abstract: |
Purpose: The proliferation of breast epithelial cells increases during the luteal phase of the menstrual cycle, when they are exposed to progesterone, suggesting that ulipristal acetate, a selective progestin-receptor modulator (SPRM), may reduce breast cell proliferation with potential use in breast cancer chemoprevention. Methods: Women aged 18–39 were randomized 1:1 to ulipristal 10-mg daily or to a combination oral contraceptive (COC) for 84 days. Participants underwent a breast biopsy and breast MRI at baseline and at end of study treatment. Proliferation of breast TDLU cells was evaluated by Ki67 immunohistochemical stain. We evaluated the breast MRIs for background parenchymal enhancement (BPE). All slides and images were masked for outcome evaluation. Results: Twenty-eight treatment-compliant participants completed the study; 25 of whom had evaluable Ki67 results at baseline and on-treatment. From baseline to end of treatment, Ki67 % positivity (Ki67%+) decreased a median of 84% in the ulipristal group (N = 13; 2-sided p (2p) = 0.040) versus a median increase of 8% in the COC group (N = 12; 2p = 0.85). Median BPE scores decreased from 3 to 1 in the ulipristal group (p = 0.008) and did not decrease in the COC group. Conclusion: Ulipristal was associated with a major decrease in Ki67%+ and BPE. Ulipristal would warrant further investigation for breast cancer chemoprevention were it not for concerns about its liver toxicity. Novel SPRMs without liver toxicity could provide a new approach to breast cancer chemoprevention. Trial registration: NCT02922127, 4 October 2016. © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. |
| Notes: |
Article -- Export Date: 1 April 2022 -- Funding details: National Institutes of Health, NIH, P30 CA008748 -- Funding details: National Cancer Institute, NCI, 5RO1 CA200795 -- Funding details: Ontario Ministry of Research, Innovation and Science, MRIS -- Funding text 1: We wish to express our sincerest gratitude to the women who volunteered to be part of this study. We also wish to express our thanks to Ariel Allen, Jacqueline Dillon, and Molly Morgan for managing the recruitment and day-to-day study conduct, to Hao Yang for anonymizing the MRIs and arranging for the presentation of only one breast from the MRI to RH for analysis. We also wish to express our thanks to Renu Nandakumar of the Biomarkers Core Laboratory at the Irving Institute for Clinical and Translational Research, home to Columbia University Irving Medical Center?s Clinical and Translational Science Award Program hub, for carrying out the ulipristal and levonorgestrel assays. -- Funding text 2: This study was supported by a grant from the National Cancer Institute (5RO1 CA200795; P.I. CLW). MCP was supported in part through the National Institutes of Health/National Cancer Institute Support Grant P30 CA008748 to Memorial Sloan Kettering Cancer Center. The study sponsors had no role in the design of the study; the collection, analysis, or interpretation of the data; the writing of the manuscript; or the decision to submit the manuscript for publication. -- Source: Scopus |
