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Correlation of rs1799793 polymorphism in ERCC2 and the clinical response to platinum-based chemotherapy in patients with triple negative breast cancer.

ABSTRACT: BACKGROUND:Polymorphisms of DNA repair genes may affect the repair capacity of DNA damages and cause different responses towards chemotherapy. Excision repair cross-complementing group 2 (ERCC2) plays an important role in the nucleotide excision repair. OBJECTIVES:The aim of this study was to investigate the association between ERCC2 single nucleotide polymorphisms (SNPs) and the response to platinum-based chemotherapy among patients with triple negative breast cancer. METHODS:In total, 60 triple negative breast cancer patients treated with platinum-based chemotherapy were studied. The clinical, pathological and treatment data of them were collected. Sequenom's MassARRAY system was used in the detection of the SNPs of ERCC2. Finally, the association between genotypes and different clinical responses among patients was analyzed. All of the patients received a platinum-based chemotherapy for 4 cycles in median and achieved an overall response rate of 66.7%, showing a comparative good response towards platinum-based chemotherapy among triple negative breast cancer. Fifty-three of the 60 patients had got the results of ERCC2 rs1799793 polymorphisms after MassARRAY detection. RESULTS:The proportion of GG genotype and GA genotype was 81.1% and 18.9% respectively. The response rate of the rs1799793 GG genotype group was 69.8%, while the GA genotype group only had a response rate of 30.0%. It turned out that the GG genotype was associated with better response towards platinum-based chemotherapy (P=0.030). CONCLUSIONS:ERCC2 rs1799793 polymorphism may be associated with the clinical sensitivity of platinum-based chemotherapy and could be a potential predictive biomarker for triple negative breast cancer patients treated with platinum compounds.

SUBMITTER: Lu J

PROVIDER: S-EPMC4402905 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Correlation of rs1799793 polymorphism in ERCC2 and the clinical response to platinum-based chemotherapy in patients with triple negative breast cancer.

Lu Jun J Zhao Haitao H Li Sha S Tian Zhongze Z Zhu Xianghui X Wang Hongyi H Fu Hua H

International journal of clinical and experimental medicine 20150215 2

<h4>Background</h4>Polymorphisms of DNA repair genes may affect the repair capacity of DNA damages and cause different responses towards chemotherapy. Excision repair cross-complementing group 2 (ERCC2) plays an important role in the nucleotide excision repair.<h4>Objectives</h4>The aim of this study was to investigate the association between ERCC2 single nucleotide polymorphisms (SNPs) and the response to platinum-based chemotherapy among patients with triple negative breast cancer.<h4>Methods< ...[more]

PMID: 25932258

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Project description:PurposeTo determine whether specific somatic copy-number alterations detectable in circulating tumor DNA (ctDNA) from patients with metastatic triple-negative breast cancer (mTNBC) are associated with sensitivity to platinum chemotherapy.Materials and methodsIn this secondary analysis of a large cohort of patients with mTNBC whose ctDNA underwent ultralow-pass whole-genome sequencing, tumor fraction and somatic copy-number alterations were derived with the ichorCNA algorithm. Seventy-two patients were identified who had received a platinum-based chemotherapy regimen in the metastatic setting. Gene-level copy-number analyses were performed with GISTIC2.0. Cytobands were associated with progression-free survival (PFS) to platinum chemotherapy using Cox proportional hazards models. The Cancer Genome Atlas and Molecular Taxonomy of Breast Cancer International Consortium data sets were interrogated for frequency of significant cytobands in primary triple-negative breast cancer (pTNBC) tumors.ResultsAmong 71 evaluable patients, 17q21 and 17q22 amplifications were most strongly associated with improved PFS with platinum chemotherapy. There were no significant differences in clinicopathologic features or (neo)adjuvant chemotherapy among patients with 17q22 amplification. Patients with 17q22 amplification (n = 17) had longer median PFS with platinum (7.0 v 3.8 months; log-rank P = .015) than patients without 17q22 amplification (n = 54), an effect that remained significant in multivariable analyses (PFS hazard ratio 0.37; 95% CI, 0.16 to 0.84; P = .02). Among 39 patients who received the nonplatinum chemotherapy agent capecitabine, there was no association between 17q22 amplification and capecitabine PFS (log-rank P = .69). In The Cancer Genome Atlas and Molecular Taxonomy of Breast Cancer International Consortium, 17q22 amplification occurred in more than 20% of both pTNBC and mTNBC tumors, whereas 17q21 was more frequently amplified in mTNBC relative to pTNBC (16% v 8.1%, P = .015).ConclusionThe 17q22 amplicon, detected by ctDNA, is associated with improved PFS with platinum chemotherapy in patients with mTNBC and warrants further investigation.

Dataset Information

Correlation of rs1799793 polymorphism in ERCC2 and the clinical response to platinum-based chemotherapy in patients with triple negative breast cancer.

Publications

Correlation of rs1799793 polymorphism in ERCC2 and the clinical response to platinum-based chemotherapy in patients with triple negative breast cancer.

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