Beneficial Effects of Mifepristone Treatment in Patients with Breast Cancer Selected by the Progesterone Receptor Isoform Ratio: Results from the MIPRA Trial
- Autores
- Elia, Andres Maximiliano; Saldain, Leo; Vanzulli, Silvia; Helguero, Luisa Alejandra; Lamb, Caroline Ana; Fabris, Victoria Teresa; Pataccini, Gabriela; Martínez Vazquez, Paula; Burruchaga, Javier; Caillet Bois, Ines; Spengler, EunicE; Acosta Haab, Gabriela; Liguori, Marcos Daniel; Castets, Alejandra; Lovisi, Silvia; Abascal, Maria Florencia; Novaro, Virginia; Sánchez, Jana; Muñoz, Javier; Belizán, José M.; Abba, Martín Carlos; Gass, Hugo Daniel; Rojas, Paola Andrea; Lanari, Claudia Lee Malvina
- Año de publicación
- 2022
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Purpose: 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 pre-surgical 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).Patients and methods: Twenty patients with 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, while others were snap-frozen to perform 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 pre- and post-treatment.Results: A 49.62% decrease in Ki67 staining was observed in all surgical specimens compared to baseline (p=0.0003). Using the prespecified response parameter (30% relative reduction), we identified 14/20 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 caspase3 expression. RNA-Seq and proteomics studies identified downregulated pathways related to cell proliferation and upregulated pathways related to immune bioprocesses and extracellular matrix remodeling.Conclusions: 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.
Fil: Elia, Andres Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Saldain, Leo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Vanzulli, Silvia. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Helguero, Luisa Alejandra. Universidade de Aveiro; Portugal
Fil: Lamb, Caroline Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Fabris, Victoria Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Pataccini, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Martínez Vazquez, Paula. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; Argentina
Fil: Burruchaga, Javier. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; Argentina
Fil: Caillet Bois, Ines. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; Argentina
Fil: Spengler, EunicE. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; Argentina
Fil: Acosta Haab, Gabriela. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; Argentina
Fil: Liguori, Marcos Daniel. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; Argentina
Fil: Castets, Alejandra. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; Argentina
Fil: Lovisi, Silvia. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; Argentina
Fil: Abascal, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Novaro, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Sánchez, Jana. Centro Nacional de Investigaciones Oncológicas; España
Fil: Muñoz, Javier. Centro Nacional de Investigaciones Oncológicas; España
Fil: Belizán, José M.. Instituto de Efectividad Clínica y Sanitaria; Argentina
Fil: Abba, Martín Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Gass, Hugo Daniel. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; Argentina
Fil: Rojas, Paola Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Lanari, Claudia Lee Malvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina - Materia
-
CÁNCER DE MAMA
RECEPTOR DE PROGESTERONA
MIFEPRISTONA
ESTUDIO CLÍNICO - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/221156
Ver los metadatos del registro completo
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Beneficial Effects of Mifepristone Treatment in Patients with Breast Cancer Selected by the Progesterone Receptor Isoform Ratio: Results from the MIPRA TrialElia, Andres MaximilianoSaldain, LeoVanzulli, SilviaHelguero, Luisa AlejandraLamb, Caroline AnaFabris, Victoria TeresaPataccini, GabrielaMartínez Vazquez, PaulaBurruchaga, JavierCaillet Bois, InesSpengler, EunicEAcosta Haab, GabrielaLiguori, Marcos DanielCastets, AlejandraLovisi, SilviaAbascal, Maria FlorenciaNovaro, VirginiaSánchez, JanaMuñoz, JavierBelizán, José M.Abba, Martín CarlosGass, Hugo DanielRojas, Paola AndreaLanari, Claudia Lee MalvinaCÁNCER DE MAMARECEPTOR DE PROGESTERONAMIFEPRISTONAESTUDIO CLÍNICOhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Purpose: 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 pre-surgical 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).Patients and methods: Twenty patients with 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, while others were snap-frozen to perform 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 pre- and post-treatment.Results: A 49.62% decrease in Ki67 staining was observed in all surgical specimens compared to baseline (p=0.0003). Using the prespecified response parameter (30% relative reduction), we identified 14/20 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 caspase3 expression. RNA-Seq and proteomics studies identified downregulated pathways related to cell proliferation and upregulated pathways related to immune bioprocesses and extracellular matrix remodeling.Conclusions: 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.Fil: Elia, Andres Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Saldain, Leo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Vanzulli, Silvia. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Helguero, Luisa Alejandra. Universidade de Aveiro; PortugalFil: Lamb, Caroline Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Fabris, Victoria Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Pataccini, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Martínez Vazquez, Paula. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; ArgentinaFil: Burruchaga, Javier. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; ArgentinaFil: Caillet Bois, Ines. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; ArgentinaFil: Spengler, EunicE. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; ArgentinaFil: Acosta Haab, Gabriela. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; ArgentinaFil: Liguori, Marcos Daniel. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; ArgentinaFil: Castets, Alejandra. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; ArgentinaFil: Lovisi, Silvia. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; ArgentinaFil: Abascal, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Novaro, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Sánchez, Jana. Centro Nacional de Investigaciones Oncológicas; EspañaFil: Muñoz, Javier. Centro Nacional de Investigaciones Oncológicas; EspañaFil: Belizán, José M.. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Abba, Martín Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Gass, Hugo Daniel. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; ArgentinaFil: Rojas, Paola Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Lanari, Claudia Lee Malvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaAmerican Association for Cancer Research2022-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/221156Elia, Andres Maximiliano; Saldain, Leo; Vanzulli, Silvia; Helguero, Luisa Alejandra; Lamb, Caroline Ana; et al.; Beneficial Effects of Mifepristone Treatment in Patients with Breast Cancer Selected by the Progesterone Receptor Isoform Ratio: Results from the MIPRA Trial; American Association for Cancer Research; Clinical Cancer Research; 29; 5; 11-2022; 866-8771078-0432CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-22-2060/710517/Beneficial-Effects-of-Mifepristone-Treatment-ininfo:eu-repo/semantics/altIdentifier/doi/10.1158/1078-0432.CCR-22-2060info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:05:55Zoai:ri.conicet.gov.ar:11336/221156instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:05:55.666CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Beneficial Effects of Mifepristone Treatment in Patients with Breast Cancer Selected by the Progesterone Receptor Isoform Ratio: Results from the MIPRA Trial |
| title |
Beneficial Effects of Mifepristone Treatment in Patients with Breast Cancer Selected by the Progesterone Receptor Isoform Ratio: Results from the MIPRA Trial |
| spellingShingle |
Beneficial Effects of Mifepristone Treatment in Patients with Breast Cancer Selected by the Progesterone Receptor Isoform Ratio: Results from the MIPRA Trial Elia, Andres Maximiliano CÁNCER DE MAMA RECEPTOR DE PROGESTERONA MIFEPRISTONA ESTUDIO CLÍNICO |
| title_short |
Beneficial Effects of Mifepristone Treatment in Patients with Breast Cancer Selected by the Progesterone Receptor Isoform Ratio: Results from the MIPRA Trial |
| title_full |
Beneficial Effects of Mifepristone Treatment in Patients with Breast Cancer Selected by the Progesterone Receptor Isoform Ratio: Results from the MIPRA Trial |
| title_fullStr |
Beneficial Effects of Mifepristone Treatment in Patients with Breast Cancer Selected by the Progesterone Receptor Isoform Ratio: Results from the MIPRA Trial |
| title_full_unstemmed |
Beneficial Effects of Mifepristone Treatment in Patients with Breast Cancer Selected by the Progesterone Receptor Isoform Ratio: Results from the MIPRA Trial |
| title_sort |
Beneficial Effects of Mifepristone Treatment in Patients with Breast Cancer Selected by the Progesterone Receptor Isoform Ratio: Results from the MIPRA Trial |
| dc.creator.none.fl_str_mv |
Elia, Andres Maximiliano Saldain, Leo Vanzulli, Silvia Helguero, Luisa Alejandra Lamb, Caroline Ana Fabris, Victoria Teresa Pataccini, Gabriela Martínez Vazquez, Paula Burruchaga, Javier Caillet Bois, Ines Spengler, EunicE Acosta Haab, Gabriela Liguori, Marcos Daniel Castets, Alejandra Lovisi, Silvia Abascal, Maria Florencia Novaro, Virginia Sánchez, Jana Muñoz, Javier Belizán, José M. Abba, Martín Carlos Gass, Hugo Daniel Rojas, Paola Andrea Lanari, Claudia Lee Malvina |
| author |
Elia, Andres Maximiliano |
| author_facet |
Elia, Andres Maximiliano Saldain, Leo Vanzulli, Silvia Helguero, Luisa Alejandra Lamb, Caroline Ana Fabris, Victoria Teresa Pataccini, Gabriela Martínez Vazquez, Paula Burruchaga, Javier Caillet Bois, Ines Spengler, EunicE Acosta Haab, Gabriela Liguori, Marcos Daniel Castets, Alejandra Lovisi, Silvia Abascal, Maria Florencia Novaro, Virginia Sánchez, Jana Muñoz, Javier Belizán, José M. Abba, Martín Carlos Gass, Hugo Daniel Rojas, Paola Andrea Lanari, Claudia Lee Malvina |
| author_role |
author |
| author2 |
Saldain, Leo Vanzulli, Silvia Helguero, Luisa Alejandra Lamb, Caroline Ana Fabris, Victoria Teresa Pataccini, Gabriela Martínez Vazquez, Paula Burruchaga, Javier Caillet Bois, Ines Spengler, EunicE Acosta Haab, Gabriela Liguori, Marcos Daniel Castets, Alejandra Lovisi, Silvia Abascal, Maria Florencia Novaro, Virginia Sánchez, Jana Muñoz, Javier Belizán, José M. Abba, Martín Carlos Gass, Hugo Daniel Rojas, Paola Andrea Lanari, Claudia Lee Malvina |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
CÁNCER DE MAMA RECEPTOR DE PROGESTERONA MIFEPRISTONA ESTUDIO CLÍNICO |
| topic |
CÁNCER DE MAMA RECEPTOR DE PROGESTERONA MIFEPRISTONA ESTUDIO CLÍNICO |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
| dc.description.none.fl_txt_mv |
Purpose: 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 pre-surgical 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).Patients and methods: Twenty patients with 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, while others were snap-frozen to perform 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 pre- and post-treatment.Results: A 49.62% decrease in Ki67 staining was observed in all surgical specimens compared to baseline (p=0.0003). Using the prespecified response parameter (30% relative reduction), we identified 14/20 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 caspase3 expression. RNA-Seq and proteomics studies identified downregulated pathways related to cell proliferation and upregulated pathways related to immune bioprocesses and extracellular matrix remodeling.Conclusions: 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. Fil: Elia, Andres Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Saldain, Leo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Vanzulli, Silvia. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Helguero, Luisa Alejandra. Universidade de Aveiro; Portugal Fil: Lamb, Caroline Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Fabris, Victoria Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Pataccini, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Martínez Vazquez, Paula. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; Argentina Fil: Burruchaga, Javier. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; Argentina Fil: Caillet Bois, Ines. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; Argentina Fil: Spengler, EunicE. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; Argentina Fil: Acosta Haab, Gabriela. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; Argentina Fil: Liguori, Marcos Daniel. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; Argentina Fil: Castets, Alejandra. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; Argentina Fil: Lovisi, Silvia. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; Argentina Fil: Abascal, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Novaro, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Sánchez, Jana. Centro Nacional de Investigaciones Oncológicas; España Fil: Muñoz, Javier. Centro Nacional de Investigaciones Oncológicas; España Fil: Belizán, José M.. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Abba, Martín Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina Fil: Gass, Hugo Daniel. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Magdalena Villegas de Martinez.; Argentina Fil: Rojas, Paola Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Lanari, Claudia Lee Malvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina |
| description |
Purpose: 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 pre-surgical 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).Patients and methods: Twenty patients with 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, while others were snap-frozen to perform 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 pre- and post-treatment.Results: A 49.62% decrease in Ki67 staining was observed in all surgical specimens compared to baseline (p=0.0003). Using the prespecified response parameter (30% relative reduction), we identified 14/20 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 caspase3 expression. RNA-Seq and proteomics studies identified downregulated pathways related to cell proliferation and upregulated pathways related to immune bioprocesses and extracellular matrix remodeling.Conclusions: 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. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022-11 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
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article |
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publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/221156 Elia, Andres Maximiliano; Saldain, Leo; Vanzulli, Silvia; Helguero, Luisa Alejandra; Lamb, Caroline Ana; et al.; Beneficial Effects of Mifepristone Treatment in Patients with Breast Cancer Selected by the Progesterone Receptor Isoform Ratio: Results from the MIPRA Trial; American Association for Cancer Research; Clinical Cancer Research; 29; 5; 11-2022; 866-877 1078-0432 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/221156 |
| identifier_str_mv |
Elia, Andres Maximiliano; Saldain, Leo; Vanzulli, Silvia; Helguero, Luisa Alejandra; Lamb, Caroline Ana; et al.; Beneficial Effects of Mifepristone Treatment in Patients with Breast Cancer Selected by the Progesterone Receptor Isoform Ratio: Results from the MIPRA Trial; American Association for Cancer Research; Clinical Cancer Research; 29; 5; 11-2022; 866-877 1078-0432 CONICET Digital CONICET |
| dc.language.none.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/https://aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-22-2060/710517/Beneficial-Effects-of-Mifepristone-Treatment-in info:eu-repo/semantics/altIdentifier/doi/10.1158/1078-0432.CCR-22-2060 |
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info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
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openAccess |
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application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf |
| dc.publisher.none.fl_str_mv |
American Association for Cancer Research |
| publisher.none.fl_str_mv |
American Association for Cancer Research |
| dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
| reponame_str |
CONICET Digital (CONICET) |
| collection |
CONICET Digital (CONICET) |
| instname_str |
Consejo Nacional de Investigaciones Científicas y Técnicas |
| repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
| repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
| _version_ |
1842269934435958784 |
| score |
13.13397 |