Dataset Information

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

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.

SUBMITTER: Mori H

PROVIDER: S-EPMC5158199 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

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

Mori Hitomi H Kubo Makoto M Nishimura Reiki R Osako Tomofumi T Arima Nobuyuki N Okumura Yasuhiro Y Okido Masayuki M Yamada Mai M Kai Masaya M Kishimoto Junji J Miyazaki Tetsuyuki T Oda Yoshinao Y Otsuka Takao T Nakamura Masafumi M

PloS one 20161215 12

<h4>Background</h4>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.<h4>Methods</h4>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 perf ...[more]

PMID: 27977696

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Project description:Triple-negative breast cancer (TNBC) constitutes a heterogeneous breast cancer subgroup with poor prognosis; survival rates are likely to be lower with TNBC compared to other breast cancer subgroups. For this disease, systemic adjuvant chemotherapy regimens often yield suboptimal clinical results. To improve treatment regimens in TNBC, identification of molecular biomarkers may help to select patients for individualized adjuvant therapy. Evidence has accumulated that determination of the methylation status of the PITX2 gene provides a predictive value in various breast cancer subgroups, either treated with endocrine-based therapy or anthracycline-containing chemotherapy. To further explore the validity of this novel predictive candidate biomarker, in the present exploratory retrospective study, determination of the PITX2 DNA-methylation status was assessed for non-metastatic TNBC patients treated with adjuvant anthracycline-based chemotherapy by molecular analysis of breast cancer tissues. The PITX2 DNA-methylation status was determined in fresh-frozen tumor tissue specimens (n=56) by methylation-specific qRT-PCR (qMSP) and the data related to disease-free and overall survival, applying an optimized DNA-methylation score of 6.35%. For non-metastatic TNBC patients treated with adjuvant systemic anthracycline-based chemotherapy, a low PITX2 DNA-methylation status (<6.35) defines TNBC patients with poor disease-free and overall survival. Univariate and multivariate analyses demonstrate the statistically independent predictive value of PITX2 DNA-methylation. For non-metastatic TNBC patients, selective determination of the PITX2 DNA-methylation status may serve as a cancer biomarker for predicting response to anthracycline-based adjuvant chemotherapy. The assay based on methylation of the PIXT2 gene can be applied to frozen and routinely available formalin-fixed, paraffin-embedded (FFPE) breast cancer tumor tissues that will not only define those TNBC patients who may benefit from anthracycline-based chemotherapy but also those who should be spared the necessity of such potentially toxic treatment. Such patients should be allocated to alternative treatment options.

Project description:BackgroundTriple-negative breast cancer (TNBC) is characterized by poor prognosis and lack of targeted therapies and biomarkers to guide decisions on adjuvant chemotherapy. Parathyroid hormone-related protein (PTHrP) is frequently overexpressed in breast cancer and involved in proliferation and metastasis, two hallmarks of poor prognosis for node-negative breast cancer. We investigated the prognostic value of PTHrP with respect to organ-specific metastasis and nodal status in TNBC.MethodsWe assessed PTHrP expression using immunohistochemistry in a clinically annotated tissue microarray for a population-based study of 314 patients newly diagnosed with TNBC, then analyzed its correlation to progression and survival using Kaplan-Meier and Cox regression analyses. The Cancer Genome Atlas (TCGA) validation analysis was performed through Bioconductor. All statistical tests were two-sided.ResultsPTHrP overexpression (160 of 290 scorable cases, 55.2%) was statistically significantly associated in univariate analysis with decreased overall survival (OS) in our cohort (P = .0055) and The Cancer Genome Atlas (P = .0018) and decreased central nervous system (CNS)-progression-free survival (P = .0029). In multivariate analysis, PTHrP was a statistically significant independent prognostic factor for CNS-progression-free survival in TNBC (hazard ratio [HR] = 5.014, 95% confidence interval [CI] = 1.421 to 17.692, P = .0122) and for OS selectively in node-negative TNBC (HR = 2.423, 95% CI = 1.129 to 5.197, P = .0231). Strikingly, PTHrP emerged as the only statistically significant prognostic factor (HR = 2.576, 95% CI = 1.019 to 6.513, P = .0456) for OS of low-clinical risk node-negative patients who did not receive adjuvant chemotherapy.ConclusionsPTHrP is a novel independent prognostic factor for CNS metastasis and adjuvant chemotherapy selection of low-clinical risk node-negative TNBC. Its predictive value needs to be prospectively assessed in clinical trials.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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