Advanced

Comparative proteome analysis revealing an 11-protein signature for aggressive triple-negative breast cancer

Liu, Ning Qing ; Stingl, Christoph ; Look, Maxime P. ; Smid, Marcel ; Braakman, René B H ; De Marchi, Tommaso LU ; Sieuwerts, Anieta M. ; Span, Paul N. ; Sweep, Fred C G J and Linderholm, Barbro K. , et al. (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)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
publishing date
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
2020-10-20 04:25:24
@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},
  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},
}