Comparative proteome analysis revealing an 11-protein signature for aggressive triple-negative breast cancer
(2014) In Journal of the National Cancer Institute 106(2).- 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... (More)
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.
(Less)
- author
- publishing date
- 2014-02
- type
- Contribution to journal
- publication status
- published
- keywords
- Adult, Aged, Antineoplastic Agents, Biomarkers, Tumor, Chemotherapy, Adjuvant, Female, Frozen Sections, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Kaplan-Meier Estimate, Middle Aged, Odds Ratio, Oligonucleotide Array Sequence Analysis, Predictive Value of Tests, Prognosis, Proteome, Reproducibility of Results, Sensitivity and Specificity, Signal Transduction, Transcriptome, Triple Negative Breast Neoplasms, Unnecessary Procedures, Comparative Study, Validation Studies
- in
- Journal of the National Cancer Institute
- volume
- 106
- issue
- 2
- article number
- djt376
- publisher
- Oxford University Press
- external identifiers
-
- pmid:24399849
- scopus:84893821461
- ISSN
- 1460-2105
- DOI
- 10.1093/jnci/djt376
- language
- English
- LU publication?
- no
- id
- 383ac58c-d24c-4945-966b-d2235b06e090
- date added to LUP
- 2017-06-27 14:27:26
- date last changed
- 2024-11-11 11:30:25
@article{383ac58c-d24c-4945-966b-d2235b06e090,
abstract = {{<p>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.</p><p>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.</p><p>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.</p><p>CONCLUSIONS: We report the first validated proteomic signature to assess the natural course of clinical TNBC.</p>}},
author = {{Liu, Ning Qing and Stingl, Christoph and Look, Maxime P. and Smid, Marcel and Braakman, René B H and De Marchi, Tommaso and Sieuwerts, Anieta M. and Span, Paul N. and Sweep, Fred C G J and Linderholm, Barbro K. and Mangia, Anita and Paradiso, Angelo and Dirix, Luc Y and Van Laere, Steven J and Luider, Theo M. and Martens, John W. M. and Foekens, John A. and Umar, Arzu}},
issn = {{1460-2105}},
keywords = {{Adult; Aged; Antineoplastic Agents; Biomarkers, Tumor; Chemotherapy, Adjuvant; Female; Frozen Sections; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Kaplan-Meier Estimate; Middle Aged; Odds Ratio; Oligonucleotide Array Sequence Analysis; Predictive Value of Tests; Prognosis; Proteome; Reproducibility of Results; Sensitivity and Specificity; Signal Transduction; Transcriptome; Triple Negative Breast Neoplasms; Unnecessary Procedures; Comparative Study; Validation Studies}},
language = {{eng}},
number = {{2}},
publisher = {{Oxford University Press}},
series = {{Journal of the National Cancer Institute}},
title = {{Comparative proteome analysis revealing an 11-protein signature for aggressive triple-negative breast cancer}},
url = {{http://dx.doi.org/10.1093/jnci/djt376}},
doi = {{10.1093/jnci/djt376}},
volume = {{106}},
year = {{2014}},
}