TY - JOUR
T1 - BRCAness as a biomarker for predicting prognosis and response to anthracycline-based adjuvant chemotherapy for patients with triple-negative breast cancer
AU - Mori, Hitomi
AU - Kubo, Makoto
AU - Nishimura, Reiki
AU - Osako, Tomofumi
AU - Arima, Nobuyuki
AU - Okumura, Yasuhiro
AU - Okido, Masayuki
AU - Yamada, Mai
AU - Kai, Masaya
AU - Kishimoto, Junji
AU - Miyazaki, Tetsuyuki
AU - Oda, Yoshinao
AU - Otsuka, Takao
AU - Nakamura, Masafumi
N1 - Funding Information:
This work was supported by the Japan Society for the Promotion of Science, KAKENHI, and by the budget demand from Ministry of Education, Culture, Sports, Science and Technology, Japan, Grant number 20591550, https://www.jsps.go.jp/j-grantsinaid/ to Makoto Kubo, and by World premier COE (core of excellence) formation for the treatment and research of pancreatic cancer (there is no grant number), http://www.mext.go.jp/en/ to Takao Otsuka. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors thank Hisako Okuma, Kaori Nomiyama, Miyuki Omori, Hiroshi Fujii, and Hiroyuki Minami for their technical assistance. We are thankful to Yasuhiro Shimoda and Arata Takahashi for performing the multiplex ligation-dependent probe amplification reactions. The authors received a Basic Science Award supported by the 38th San Antonio Breast Cancer Symposium, 2015.
Publisher Copyright:
© 2016 Mori et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/12
Y1 - 2016/12
N2 - 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 anthracyclinebased adjuvant chemotherapy for patients with TNBCs.
AB - 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 anthracyclinebased adjuvant chemotherapy for patients with TNBCs.
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U2 - 10.1371/journal.pone.0167016
DO - 10.1371/journal.pone.0167016
M3 - Article
C2 - 27977696
AN - SCOPUS:85006304514
SN - 1932-6203
VL - 11
JO - PLoS One
JF - PLoS One
IS - 12
M1 - e0167016
ER -