Comparative proteome analysis revealing an 11-protein signature for aggressive triple-negative breast cancer.
J Natl Cancer Inst
; 106(2): djt376, 2014 Feb.
Article
em En
| MEDLINE
| ID: mdl-24399849
ABSTRACT
BACKGROUND:
Clinical outcome of patients with triple-negative breast cancer (TNBC) is highly variable. This study aims to identify and validate a prognostic protein signature for TNBC patients to reduce unnecessary adjuvant systemic therapy.METHODS:
Frozen primary tumors were collected from 126 lymph node-negative and adjuvant therapy-naive TNBC patients. These samples were used for global proteome profiling in two series an in-house training (n = 63) and a multicenter test (n = 63) set. Patients who remained free of distant metastasis for a minimum of 5 years after surgery were defined as having good prognosis. Cox regression analysis was performed to develop a prognostic signature, which was independently validated. All statistical tests were two-sided.RESULTS:
An 11-protein signature was developed in the training set (median follow-up for good-prognosis patients = 117 months) and subsequently validated in the test set (median follow-up for good-prognosis patients = 108 months) showing 89.5% sensitivity (95% confidence interval [CI] = 69.2% to 98.1%), 70.5% specificity (95% CI = 61.7% to 74.2%), 56.7% positive predictive value (95% CI = 43.8% to 62.1%), and 93.9% negative predictive value (95% CI = 82.3% to 98.9%) for poor-prognosis patients. The predicted poor-prognosis patients had higher risk to develop distant metastasis than the predicted good-prognosis patients in univariate (hazard ratio [HR] = 13.15; 95% CI = 3.03 to 57.07; P = .001) and multivariable (HR = 12.45; 95% CI = 2.67 to 58.11; P = .001) analysis. Furthermore, the predicted poor-prognosis group had statistically significantly more breast cancer-specific mortality. Using our signature as guidance, more than 60% of patients would have been exempted from unnecessary adjuvant chemotherapy compared with conventional prognostic guidelines.CONCLUSIONS:
We report the first validated proteomic signature to assess the natural course of clinical TNBC.
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Base de dados:
MEDLINE
Assunto principal:
Regulação Neoplásica da Expressão Gênica
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Análise de Sequência com Séries de Oligonucleotídeos
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Proteoma
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Perfilação da Expressão Gênica
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Transcriptoma
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Neoplasias de Mama Triplo Negativas
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Antineoplásicos
Tipo de estudo:
Clinical_trials
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Diagnostic_studies
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Etiology_studies
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Guideline
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Prognostic_studies
Limite:
Adult
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Aged
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Female
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article