Abstract
BackgroundTriple-negative breast cancer (TNBC) accounts for 15–20% of all breast cancers and usually requires the administration of adjuvant chemotherapy after surgery but even with this treatment many patients still suffer from a relapse. The main objective of this study was to identify proteomics-based biomarkers that predict the response to standard adjuvant chemotherapy, so that patients at are not going to benefit from it can be offered therapeutic alternatives.MethodsWe analyzed the proteome of a retrospective series of formalin-fixed, paraffin-embedded TNBC tissue applying high-throughput label-free quantitative proteomics. We identified several protein signatures with predictive value, which were validated with quantitative targeted proteomics in an independent cohort of patients and further evaluated in publicly available transcriptomics data.ResultsUsing univariate Cox analysis, a panel of 18 proteins was significantly associated with distant metastasis-free survival of patients (p<0.01). A reduced 5-protein profile with prognostic value was identified and its prediction performance was assessed in an independent targeted proteomics experiment and a publicly available transcriptomics dataset. Predictor P5 including peptides from proteins RAC2, RAB6A, BIEA and IPYR was the best performance protein combination in predicting relapse after adjuvant chemotherapy in TNBC patients.ConclusionsThis study identified a protein combination signature that complements histopathological prognostic factors in TNBC treated with adjuvant chemotherapy. The protein signature can be used in paraffin-embedded samples, and after a prospective validation in independent series, it could be used as predictive clinical test in order to recommend participation in clinical trials or a more exhaustive follow-up.
Highlights
Breast cancer is one of the leading causes of death among women in developed countries
This study identified a protein combination signature that complements histopathological prognostic factors in Triple-negative breast cancer (TNBC) treated with adjuvant chemotherapy
Triple-negative breast cancer (TNBC) accounts for one fifth of all breast cancers, and they are usually treated with the administration of adjuvant chemotherapy after surgery, many patients have a relapse
Summary
Breast cancer is one of the leading causes of death among women in developed countries. Triple-negative breast cancer (TNBC) is associated with a poor outcome when compared with other subtypes, due to its aggressive behavior and limited therapeutic options [1]. Several gene expression profiling evidenced the existence of distinct molecular subgroups of TNBC [3,4,5]. These molecular studies have not yet allowed the stratification of patients into categories with different prognosis and response to specific treatments. Triple-negative breast cancer (TNBC) accounts for 15–20% of all breast cancers and usually requires the administration of adjuvant chemotherapy after surgery but even with this treatment many patients still suffer from a relapse. The main objective of this study was to identify proteomics-based biomarkers that predict the response to standard adjuvant chemotherapy, so that patients at are not going to benefit from it can be offered therapeutic alternatives
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