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| Status |
Public on Oct 17, 2022 |
| Title |
Beneficial effects of mifepristone treatment in breast cancer patients selected by the progesterone receptor isoform ratio: Results from the MIPRA trial |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Background: Preclinical data suggest that antiprogestins inhibit the growth of luminal breast carcinomas expressing higher levels of progesterone receptor isoform A (PRA) than isoform B (PRB). Thus, we designed a pre-surgical window of opportunity trial to determine the therapeutic effects of mifepristone in breast cancer patients selected by their high PRA/PRB isoform ratio (MIPRA; NCT02651844). Patients and Methods. Twenty patients bearing luminal breast carcinomas with PRA/PRB>1.5 (determined by Western blots), and PR ≥50%, naive from previous treatment, were included for mifepristone treatment (200 mg/day p.o.; 14 days). Core needle biopsies (CNB) and surgical samples were formalin-fixed for immunohistochemical studies, and others were snap-frozen to perform RNA-Seq, proteomics, and/or Western blots studies. Plasma mifepristone levels were determined by mass spectrometry. The primary endpoint was the comparison of Ki-67 expression pre- and post-treatment. Results: A 49.62% decrease in Ki-67 staining was registered in all surgical specimens compared to baseline (p=0.0003). Using the pre-specified response parameter (30% relative reduction) we identified 14/20 responders. Mifepristone induced gland differentiation, an increase in tumor-infiltrating lymphocytes, a decrease in hormone receptors and pSer118ER expression, and an increase in calregulin, p21, p15, and activated caspase3 expression. RNA-Seq and proteomics studies identified downregulated pathways related to cell proliferation and upregulation of those related to immune bioprocesses and extracellular matrix re-modeling pathways. Conclusion: Our results support the use of mifepristone in luminal breast cancer patients with high PRA/PRB ratios. The combined effects of mifepristone with estrogen receptor modulators deserves clinic evaluation in these patients, to improve endocrine treatment responsiveness.
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| Overall design |
Eight patients bearing luminal breast carcinomas and naive from previous treatment, were treated with mifepristone (200 mg/day p.o.; 14 days). Core needle biopsies (CNB) and surgical samples were obtained from pre- and post-treatment respectivelly, and were snap-frozen to perform RNA-Seq.
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| Contributor(s) |
Lanari C, Elía A |
| Citation(s) |
36269797 |
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| Submission date |
Sep 04, 2022 |
| Last update date |
Jan 16, 2023 |
| Contact name |
Martin Carlos Abba |
| E-mail(s) |
mcabba@gmail.com
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| Phone |
054-221-4236711
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| Organization name |
School of Medical Sciences - UNLP
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| Lab |
CINIBA
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| Street address |
60 y 120
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| City |
La Plata |
| State/province |
Buenos Aires |
| ZIP/Postal code |
1900 |
| Country |
Argentina |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA876758 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE212690_normalized_counts.txt.gz |
2.1 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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