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. 2016 Dec 15;11(12):e0167016.
doi: 10.1371/journal.pone.0167016. eCollection 2016.

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

Hitomi Mori  1 , Makoto Kubo  1 , Reiki Nishimura  2 , Tomofumi Osako  2 , Nobuyuki Arima  3 , Yasuhiro Okumura  4 , Masayuki Okido  5 , Mai Yamada  1 , Masaya Kai  1 , Junji Kishimoto  6 , Tetsuyuki Miyazaki  7 , Yoshinao Oda  7 , Takao Otsuka  1 , Masafumi Nakamura  1
Affiliations

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

Hitomi Mori et al. PLoS One. .

Abstract

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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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Kaplan–Meier analysis of patients with TNBC (n = 262).
(A) Recurrence-free survival of BRCAness tumors versus non-BRCAness tumors. (B) Overall survival of BRCAness tumors versus non-BRCAness tumors.
Fig 2
Fig 2. Kaplan–Meier analysis of patients who received anthracycline-based adjuvant chemotherapy versus non-anthracycline-based adjuvant chemotherapy.
(A) Recurrence-free survival (RFS) of BRCAness tumors (n = 126). (B) Overall survival (OS) of BRCAness tumors (n = 126). (C) RFS of non-BRCAness tumors (n = 53). (D) OS of non-BRCAness tumors (n = 53). Anthracycline or Anthra, anthracycline-based adjuvant chemotherapy; Non-Anthracycline or Non-Anthra, non-anthracycline-based adjuvant chemotherapy.
Fig 3
Fig 3. Kaplan–Meier analysis of patients with BRCAness tumors versus non-BRCAness tumors.
(A) RFS of patients who received adjuvant chemotherapy (n = 179). (B) OS of patients who received adjuvant chemotherapy (n = 179). (C) Recurrence-free survival (RFS) of patients who received no treatment (n = 82). (D) Overall survival (OS) of patients who received no treatment (n = 82).
See this image and copyright information in PMC

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