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Prognostic relevance of DNA damage and repair biomarkers in elderly patients with hormone-receptor-positive breast cancer treated with neoadjuvant hormone therapy: evidence from the real-world setting

BACKGROUND: The logic behind the outcome of endocrine therapy in breast cancer has long remained poorly understood. The prognostic role of DNA damage and repair biomarkers (DDR) was explored in postmenopausal, hormone-receptor-positive breast cancer patients treated with neoadjuvant hormone therapy...

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Autores principales: Di Benedetto, Anna, Ercolani, Cristiana, Pizzuti, Laura, Angelucci, Domenico, Sergi, Domenico, Marinelli, Camilla, Iezzi, Laura, Sperati, Francesca, Terrenato, Irene, Mazzotta, Marco, Mariani, Luciano, Vizza, Enrico, Paoletti, Giancarlo, Tomao, Silverio, Maugeri-Saccà, Marcello, Barba, Maddalena, Tinari, Nicola, Natoli, Clara, Ciliberto, Gennaro, Grassadonia, Antonino, Vici, Patrizia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700857/
https://www.ncbi.nlm.nih.gov/pubmed/31452691
http://dx.doi.org/10.1177/1758835919853192
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author Di Benedetto, Anna
Ercolani, Cristiana
Pizzuti, Laura
Angelucci, Domenico
Sergi, Domenico
Marinelli, Camilla
Iezzi, Laura
Sperati, Francesca
Terrenato, Irene
Mazzotta, Marco
Mariani, Luciano
Vizza, Enrico
Paoletti, Giancarlo
Tomao, Silverio
Maugeri-Saccà, Marcello
Barba, Maddalena
Tinari, Nicola
Natoli, Clara
Ciliberto, Gennaro
Grassadonia, Antonino
Vici, Patrizia
author_facet Di Benedetto, Anna
Ercolani, Cristiana
Pizzuti, Laura
Angelucci, Domenico
Sergi, Domenico
Marinelli, Camilla
Iezzi, Laura
Sperati, Francesca
Terrenato, Irene
Mazzotta, Marco
Mariani, Luciano
Vizza, Enrico
Paoletti, Giancarlo
Tomao, Silverio
Maugeri-Saccà, Marcello
Barba, Maddalena
Tinari, Nicola
Natoli, Clara
Ciliberto, Gennaro
Grassadonia, Antonino
Vici, Patrizia
author_sort Di Benedetto, Anna
collection PubMed
description BACKGROUND: The logic behind the outcome of endocrine therapy in breast cancer has long remained poorly understood. The prognostic role of DNA damage and repair biomarkers (DDR) was explored in postmenopausal, hormone-receptor-positive breast cancer patients treated with neoadjuvant hormone therapy (NAHT). METHODS: Data on 55 patients were included. The phosphorylated ataxia-teleangectasia and Rad3-related protein (pATR), phosphorylated ataxia-telangiectasia mutated (ATM) kinase, and phosphorylated H2A Histone Family Member X (γ-H2AX) were evaluated by immunohistochemistry in paired tissues collected at baseline and following NAHT. Biomarkers were considered both singularly and within signatures. Ki-67 percentage change was the primary biomarker endpoint. Classical endpoints were also considered. RESULTS: The most favorable Ki-67 outcome was associated with the γ-H2AX/pATM signature (p = 0.011). In models of Ki-67 reduction, ‘luminal B’ subtype, higher grade of anaplasia, and the γ-H2AX/pATM signature tested as significant (p < 0.05 for all). Results were confirmed in multivariate analysis. No association was observed with pathologic response. An increase of ∆γ-H2AX in paired breast tissues was associated with longer event-free survival (p = 0.027) and overall survival (p = 0.042). In Cox models, both survival outcomes were solely affected by grade of anaplasia, with less favorable prognosis in the highest grades (p < 0.05 for both). CONCLUSIONS: We report novel evidence of the prognostic role of DDR biomarkers on important patient outcomes in postmenopausal hormone-receptor-positive breast cancer patients treated with NAHT. If confirmed in future and adequately sized trials, our results may help inform therapeutic decisions and clarify underlying biological mechanisms.
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spelling pubmed-67008572019-08-26 Prognostic relevance of DNA damage and repair biomarkers in elderly patients with hormone-receptor-positive breast cancer treated with neoadjuvant hormone therapy: evidence from the real-world setting Di Benedetto, Anna Ercolani, Cristiana Pizzuti, Laura Angelucci, Domenico Sergi, Domenico Marinelli, Camilla Iezzi, Laura Sperati, Francesca Terrenato, Irene Mazzotta, Marco Mariani, Luciano Vizza, Enrico Paoletti, Giancarlo Tomao, Silverio Maugeri-Saccà, Marcello Barba, Maddalena Tinari, Nicola Natoli, Clara Ciliberto, Gennaro Grassadonia, Antonino Vici, Patrizia Ther Adv Med Oncol Original Research BACKGROUND: The logic behind the outcome of endocrine therapy in breast cancer has long remained poorly understood. The prognostic role of DNA damage and repair biomarkers (DDR) was explored in postmenopausal, hormone-receptor-positive breast cancer patients treated with neoadjuvant hormone therapy (NAHT). METHODS: Data on 55 patients were included. The phosphorylated ataxia-teleangectasia and Rad3-related protein (pATR), phosphorylated ataxia-telangiectasia mutated (ATM) kinase, and phosphorylated H2A Histone Family Member X (γ-H2AX) were evaluated by immunohistochemistry in paired tissues collected at baseline and following NAHT. Biomarkers were considered both singularly and within signatures. Ki-67 percentage change was the primary biomarker endpoint. Classical endpoints were also considered. RESULTS: The most favorable Ki-67 outcome was associated with the γ-H2AX/pATM signature (p = 0.011). In models of Ki-67 reduction, ‘luminal B’ subtype, higher grade of anaplasia, and the γ-H2AX/pATM signature tested as significant (p < 0.05 for all). Results were confirmed in multivariate analysis. No association was observed with pathologic response. An increase of ∆γ-H2AX in paired breast tissues was associated with longer event-free survival (p = 0.027) and overall survival (p = 0.042). In Cox models, both survival outcomes were solely affected by grade of anaplasia, with less favorable prognosis in the highest grades (p < 0.05 for both). CONCLUSIONS: We report novel evidence of the prognostic role of DDR biomarkers on important patient outcomes in postmenopausal hormone-receptor-positive breast cancer patients treated with NAHT. If confirmed in future and adequately sized trials, our results may help inform therapeutic decisions and clarify underlying biological mechanisms. SAGE Publications 2019-08-18 /pmc/articles/PMC6700857/ /pubmed/31452691 http://dx.doi.org/10.1177/1758835919853192 Text en © The Author(s), 2019 http://www.creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Research
Di Benedetto, Anna
Ercolani, Cristiana
Pizzuti, Laura
Angelucci, Domenico
Sergi, Domenico
Marinelli, Camilla
Iezzi, Laura
Sperati, Francesca
Terrenato, Irene
Mazzotta, Marco
Mariani, Luciano
Vizza, Enrico
Paoletti, Giancarlo
Tomao, Silverio
Maugeri-Saccà, Marcello
Barba, Maddalena
Tinari, Nicola
Natoli, Clara
Ciliberto, Gennaro
Grassadonia, Antonino
Vici, Patrizia
Prognostic relevance of DNA damage and repair biomarkers in elderly patients with hormone-receptor-positive breast cancer treated with neoadjuvant hormone therapy: evidence from the real-world setting
title Prognostic relevance of DNA damage and repair biomarkers in elderly patients with hormone-receptor-positive breast cancer treated with neoadjuvant hormone therapy: evidence from the real-world setting
title_full Prognostic relevance of DNA damage and repair biomarkers in elderly patients with hormone-receptor-positive breast cancer treated with neoadjuvant hormone therapy: evidence from the real-world setting
title_fullStr Prognostic relevance of DNA damage and repair biomarkers in elderly patients with hormone-receptor-positive breast cancer treated with neoadjuvant hormone therapy: evidence from the real-world setting
title_full_unstemmed Prognostic relevance of DNA damage and repair biomarkers in elderly patients with hormone-receptor-positive breast cancer treated with neoadjuvant hormone therapy: evidence from the real-world setting
title_short Prognostic relevance of DNA damage and repair biomarkers in elderly patients with hormone-receptor-positive breast cancer treated with neoadjuvant hormone therapy: evidence from the real-world setting
title_sort prognostic relevance of dna damage and repair biomarkers in elderly patients with hormone-receptor-positive breast cancer treated with neoadjuvant hormone therapy: evidence from the real-world setting
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700857/
https://www.ncbi.nlm.nih.gov/pubmed/31452691
http://dx.doi.org/10.1177/1758835919853192
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