We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Comparative proteome analysis revealing an 11-protein signature for aggressive triple-negative breast cancer.
- Authors
Liu, Ning Qing; Stingl, Christoph; Look, Maxime P; Smid, Marcel; Braakman, René B H; De Marchi, Tommaso; Sieuwerts, Anieta M; Span, Paul N; Sweep, Fred C G J; Linderholm, Barbro K; Mangia, Anita; Paradiso, Angelo; Dirix, Luc Y; Van Laere, Steven J; Luider, Theo M; Martens, John W M; Foekens, John A; Umar, Arzu
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>We report the first validated proteomic signature to assess the natural course of clinical TNBC.
- Publication
JNCI: Journal of the National Cancer Institute, 2014, Vol 106, Issue 2, pdjt376
- ISSN
0027-8874
- Publication type
journal article
- DOI
10.1093/jnci/djt376