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BRCAness as a Biomarker for Predicting Prognosis and Response to Anthracycline-Based Adjuvant Chemotherapy for Patients with Triple-Negative Breast Cancer

BACKGROUND: Triple-negative breast cancer (TNBC) is a heterogeneous tumor that encompasses many different subclasses of the disease. In this study, we assessed BRCAness, defined as the shared characteristics between sporadic and BRCA1-mutated tumors, in a large cohort of TNBC cases. METHODS: The BRC...

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Autores principales: Mori, Hitomi, Kubo, Makoto, Nishimura, Reiki, Osako, Tomofumi, Arima, Nobuyuki, Okumura, Yasuhiro, Okido, Masayuki, Yamada, Mai, Kai, Masaya, Kishimoto, Junji, Miyazaki, Tetsuyuki, Oda, Yoshinao, Otsuka, Takao, Nakamura, Masafumi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5158199/
https://www.ncbi.nlm.nih.gov/pubmed/27977696
http://dx.doi.org/10.1371/journal.pone.0167016
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author Mori, Hitomi
Kubo, Makoto
Nishimura, Reiki
Osako, Tomofumi
Arima, Nobuyuki
Okumura, Yasuhiro
Okido, Masayuki
Yamada, Mai
Kai, Masaya
Kishimoto, Junji
Miyazaki, Tetsuyuki
Oda, Yoshinao
Otsuka, Takao
Nakamura, Masafumi
author_facet Mori, Hitomi
Kubo, Makoto
Nishimura, Reiki
Osako, Tomofumi
Arima, Nobuyuki
Okumura, Yasuhiro
Okido, Masayuki
Yamada, Mai
Kai, Masaya
Kishimoto, Junji
Miyazaki, Tetsuyuki
Oda, Yoshinao
Otsuka, Takao
Nakamura, Masafumi
author_sort Mori, Hitomi
collection PubMed
description BACKGROUND: Triple-negative breast cancer (TNBC) is a heterogeneous tumor that encompasses many different subclasses of the disease. In this study, we assessed BRCAness, defined as the shared characteristics between sporadic and BRCA1-mutated tumors, in a large cohort of TNBC cases. METHODS: The BRCAness of 262 patients with primary TNBCs resected between January 2004 and December 2014 was determined through the isolation of DNA from tumor tissue. Classification of BRCAness was performed using multiple ligation-dependent probe amplification (MLPA). The tumor subtypes were determined immunohistochemically using resected specimens. RESULTS: Of the 262 TNBCs, the results of the MLPA assays showed that 174 (66.4%) tumors had BRCAness. Patients with BRCAness tumors were younger than patients with non-BRCAness tumors (P = 0.003). There was no significant difference between the two groups regarding their pathological stages. The BRCAness group had a significantly shorter recurrence-free survival (RFS) compared with the non-BRCAness group (P = 0.04) and had a shorter overall survival (OS) although this did not reach statistical significance. Adjuvant treatments with anthracycline-based regimens provided significantly greater benefits to the BRCAness group (P = 0.003 for RFS, and P = 0.03 for OS). Multivariate Cox proportional hazard model analysis showed that BRCAness was an independent negative prognostic factor, and the anthracycline-based adjuvant chemotherapy was an independent positive prognostic factor for both RFS and OS in TNBC. CONCLUSIONS: The 66.4% patients of TNBCs showed BRCAness. BRCAness is essential as a biomarker in the subclassification of TNBCs and might be of use for predicting their prognosis. Furthermore, this biomarker might be a predictive factor for the effectiveness of anthracycline-based adjuvant chemotherapy for patients with TNBCs.
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spelling pubmed-51581992016-12-21 BRCAness as a Biomarker for Predicting Prognosis and Response to Anthracycline-Based Adjuvant Chemotherapy for Patients with Triple-Negative Breast Cancer Mori, Hitomi Kubo, Makoto Nishimura, Reiki Osako, Tomofumi Arima, Nobuyuki Okumura, Yasuhiro Okido, Masayuki Yamada, Mai Kai, Masaya Kishimoto, Junji Miyazaki, Tetsuyuki Oda, Yoshinao Otsuka, Takao Nakamura, Masafumi PLoS One Research Article BACKGROUND: Triple-negative breast cancer (TNBC) is a heterogeneous tumor that encompasses many different subclasses of the disease. In this study, we assessed BRCAness, defined as the shared characteristics between sporadic and BRCA1-mutated tumors, in a large cohort of TNBC cases. METHODS: The BRCAness of 262 patients with primary TNBCs resected between January 2004 and December 2014 was determined through the isolation of DNA from tumor tissue. Classification of BRCAness was performed using multiple ligation-dependent probe amplification (MLPA). The tumor subtypes were determined immunohistochemically using resected specimens. RESULTS: Of the 262 TNBCs, the results of the MLPA assays showed that 174 (66.4%) tumors had BRCAness. Patients with BRCAness tumors were younger than patients with non-BRCAness tumors (P = 0.003). There was no significant difference between the two groups regarding their pathological stages. The BRCAness group had a significantly shorter recurrence-free survival (RFS) compared with the non-BRCAness group (P = 0.04) and had a shorter overall survival (OS) although this did not reach statistical significance. Adjuvant treatments with anthracycline-based regimens provided significantly greater benefits to the BRCAness group (P = 0.003 for RFS, and P = 0.03 for OS). Multivariate Cox proportional hazard model analysis showed that BRCAness was an independent negative prognostic factor, and the anthracycline-based adjuvant chemotherapy was an independent positive prognostic factor for both RFS and OS in TNBC. CONCLUSIONS: The 66.4% patients of TNBCs showed BRCAness. BRCAness is essential as a biomarker in the subclassification of TNBCs and might be of use for predicting their prognosis. Furthermore, this biomarker might be a predictive factor for the effectiveness of anthracycline-based adjuvant chemotherapy for patients with TNBCs. Public Library of Science 2016-12-15 /pmc/articles/PMC5158199/ /pubmed/27977696 http://dx.doi.org/10.1371/journal.pone.0167016 Text en © 2016 Mori et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Mori, Hitomi
Kubo, Makoto
Nishimura, Reiki
Osako, Tomofumi
Arima, Nobuyuki
Okumura, Yasuhiro
Okido, Masayuki
Yamada, Mai
Kai, Masaya
Kishimoto, Junji
Miyazaki, Tetsuyuki
Oda, Yoshinao
Otsuka, Takao
Nakamura, Masafumi
BRCAness as a Biomarker for Predicting Prognosis and Response to Anthracycline-Based Adjuvant Chemotherapy for Patients with Triple-Negative Breast Cancer
title BRCAness as a Biomarker for Predicting Prognosis and Response to Anthracycline-Based Adjuvant Chemotherapy for Patients with Triple-Negative Breast Cancer
title_full BRCAness as a Biomarker for Predicting Prognosis and Response to Anthracycline-Based Adjuvant Chemotherapy for Patients with Triple-Negative Breast Cancer
title_fullStr BRCAness as a Biomarker for Predicting Prognosis and Response to Anthracycline-Based Adjuvant Chemotherapy for Patients with Triple-Negative Breast Cancer
title_full_unstemmed BRCAness as a Biomarker for Predicting Prognosis and Response to Anthracycline-Based Adjuvant Chemotherapy for Patients with Triple-Negative Breast Cancer
title_short BRCAness as a Biomarker for Predicting Prognosis and Response to Anthracycline-Based Adjuvant Chemotherapy for Patients with Triple-Negative Breast Cancer
title_sort brcaness as a biomarker for predicting prognosis and response to anthracycline-based adjuvant chemotherapy for patients with triple-negative breast cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5158199/
https://www.ncbi.nlm.nih.gov/pubmed/27977696
http://dx.doi.org/10.1371/journal.pone.0167016
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