HORMAD1 overexpression predicts response to anthracycline–cyclophosphamide and survival in triple‐negative breast cancers
Triple negative breast cancers (TNBCs) represent 15–20% of all breast cancers and are associated with higher recurrence and distant metastasis rate. Standard of care for early stage TNBC is anthracyclines combined with cyclophosphamide (AC) followed by taxanes, in the neo‐adjuvant or adjuvant settin...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-10-01
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| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.13412 |
| _version_ | 1797665751164780544 |
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| author | Rania El‐Botty Sophie Vacher Juliette Mainguené Adrien Briaux Sabrina Ibadioune Ahmed Dahmani Elodie Montaudon Fariba Nemati Léa Huguet Laura Sourd Ludivine Morriset Sophie Château‐Joubert Thierry Dubois Virginie Maire Rosette Lidereau Audrey Rapinat David Gentien Florence Coussy Ivan Bièche Elisabetta Marangoni |
| author_facet | Rania El‐Botty Sophie Vacher Juliette Mainguené Adrien Briaux Sabrina Ibadioune Ahmed Dahmani Elodie Montaudon Fariba Nemati Léa Huguet Laura Sourd Ludivine Morriset Sophie Château‐Joubert Thierry Dubois Virginie Maire Rosette Lidereau Audrey Rapinat David Gentien Florence Coussy Ivan Bièche Elisabetta Marangoni |
| author_sort | Rania El‐Botty |
| collection | DOAJ |
| description | Triple negative breast cancers (TNBCs) represent 15–20% of all breast cancers and are associated with higher recurrence and distant metastasis rate. Standard of care for early stage TNBC is anthracyclines combined with cyclophosphamide (AC) followed by taxanes, in the neo‐adjuvant or adjuvant setting. This work aimed to identify predictive biomarkers of AC response in patient‐derived xenograft (PDX) models of TNBC and to validate them in the clinical setting. By gene and protein expression analysis of 39 PDX with different responses to AC, we found that high expression of HORMAD1 was associated with better response to AC. Both gene and protein expression were associated with promoter hypomethylation. In a cohort of 526 breast cancer patients, HORMAD1 was overexpressed in 71% of TNBC. In a second cohort of 186 TNBC patients treated with AC, HORMAD1 expression was associated with longer metastasis‐free survival (MFS). In summary, HORMAD1 overexpression was predictive of an improved response to AC in PDX and is an independent prognostic factor in TNBC patients treated with AC. |
| first_indexed | 2024-03-11T19:48:23Z |
| format | Article |
| id | doaj.art-544d9d964bc94114b651429060007609 |
| institution | Directory Open Access Journal |
| issn | 1574-7891 1878-0261 |
| language | English |
| last_indexed | 2024-03-11T19:48:23Z |
| publishDate | 2023-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj.art-544d9d964bc94114b6514290600076092023-10-05T15:36:11ZengWileyMolecular Oncology1574-78911878-02612023-10-0117102017202810.1002/1878-0261.13412HORMAD1 overexpression predicts response to anthracycline–cyclophosphamide and survival in triple‐negative breast cancersRania El‐Botty0Sophie Vacher1Juliette Mainguené2Adrien Briaux3Sabrina Ibadioune4Ahmed Dahmani5Elodie Montaudon6Fariba Nemati7Léa Huguet8Laura Sourd9Ludivine Morriset10Sophie Château‐Joubert11Thierry Dubois12Virginie Maire13Rosette Lidereau14Audrey Rapinat15David Gentien16Florence Coussy17Ivan Bièche18Elisabetta Marangoni19Translational Research Department, Institut Curie PSL Research University Paris FranceDepartment of Genetics, Institut Curie PSL Research University Paris FranceDepartment of Genetics, Institut Curie PSL Research University Paris FranceDepartment of Genetics, Institut Curie PSL Research University Paris FranceDepartment of Genetics, Institut Curie PSL Research University Paris FranceTranslational Research Department, Institut Curie PSL Research University Paris FranceTranslational Research Department, Institut Curie PSL Research University Paris FranceTranslational Research Department, Institut Curie PSL Research University Paris FranceTranslational Research Department, Institut Curie PSL Research University Paris FranceTranslational Research Department, Institut Curie PSL Research University Paris FranceTranslational Research Department, Institut Curie PSL Research University Paris FranceBioPole Alfort, Ecole Nationale Vétérinaire d'Alfort Maisons Alfort FranceTranslational Research Department, Institut Curie PSL Research University Paris FranceTranslational Research Department, Institut Curie PSL Research University Paris FranceDepartment of Genetics, Institut Curie PSL Research University Paris FranceTranslational Research Department, Institut Curie PSL Research University Paris FranceTranslational Research Department, Institut Curie PSL Research University Paris FranceDepartment of Genetics, Institut Curie PSL Research University Paris FranceDepartment of Genetics, Institut Curie PSL Research University Paris FranceTranslational Research Department, Institut Curie PSL Research University Paris FranceTriple negative breast cancers (TNBCs) represent 15–20% of all breast cancers and are associated with higher recurrence and distant metastasis rate. Standard of care for early stage TNBC is anthracyclines combined with cyclophosphamide (AC) followed by taxanes, in the neo‐adjuvant or adjuvant setting. This work aimed to identify predictive biomarkers of AC response in patient‐derived xenograft (PDX) models of TNBC and to validate them in the clinical setting. By gene and protein expression analysis of 39 PDX with different responses to AC, we found that high expression of HORMAD1 was associated with better response to AC. Both gene and protein expression were associated with promoter hypomethylation. In a cohort of 526 breast cancer patients, HORMAD1 was overexpressed in 71% of TNBC. In a second cohort of 186 TNBC patients treated with AC, HORMAD1 expression was associated with longer metastasis‐free survival (MFS). In summary, HORMAD1 overexpression was predictive of an improved response to AC in PDX and is an independent prognostic factor in TNBC patients treated with AC.https://doi.org/10.1002/1878-0261.13412AC sensitivitybiomarkerHORMAD1TNBC |
| spellingShingle | Rania El‐Botty Sophie Vacher Juliette Mainguené Adrien Briaux Sabrina Ibadioune Ahmed Dahmani Elodie Montaudon Fariba Nemati Léa Huguet Laura Sourd Ludivine Morriset Sophie Château‐Joubert Thierry Dubois Virginie Maire Rosette Lidereau Audrey Rapinat David Gentien Florence Coussy Ivan Bièche Elisabetta Marangoni HORMAD1 overexpression predicts response to anthracycline–cyclophosphamide and survival in triple‐negative breast cancers Molecular Oncology AC sensitivity biomarker HORMAD1 TNBC |
| title | HORMAD1 overexpression predicts response to anthracycline–cyclophosphamide and survival in triple‐negative breast cancers |
| title_full | HORMAD1 overexpression predicts response to anthracycline–cyclophosphamide and survival in triple‐negative breast cancers |
| title_fullStr | HORMAD1 overexpression predicts response to anthracycline–cyclophosphamide and survival in triple‐negative breast cancers |
| title_full_unstemmed | HORMAD1 overexpression predicts response to anthracycline–cyclophosphamide and survival in triple‐negative breast cancers |
| title_short | HORMAD1 overexpression predicts response to anthracycline–cyclophosphamide and survival in triple‐negative breast cancers |
| title_sort | hormad1 overexpression predicts response to anthracycline cyclophosphamide and survival in triple negative breast cancers |
| topic | AC sensitivity biomarker HORMAD1 TNBC |
| url | https://doi.org/10.1002/1878-0261.13412 |
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