Comparative Proteome Analysis Revealing an 11-Protein Signature for Aggressive Triple-Negative Breast Cancer

Ningqing Liu, Christoph Stingl, Maxime Look, Marcel Smid, Rene Braakman, Tommaso Marchi, Anieta Sieuwerts, PN Span, FCGJ Sweep, BK Linderholm, A Mangia, A Paradiso, LY Dirix, SJ Van Laere, Theo Luider, John Martens, John Foekens, Arzu Umar

Research output: Contribution to journalArticleAcademicpeer-review

40 Citations (Scopus)
1 Downloads (Pure)

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.
Original languageUndefined/Unknown
JournalJournal of the National Cancer Institute
Volume106
Issue number2
DOIs
Publication statusPublished - 2014

Cite this