Abstract
Abstract Background: Triple-negative breast cancer (TNBC) is a complex heterogeneous disease characterized by the absence of three hallmark receptors: human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR). Compared to other breast cancer subtypes, TNBC is more aggressive, has a higher prevalence in African Americans, and more frequently affects younger patients. Currently, TNBC lacks clinically-accepted targets for tailored therapy, warranting the need for candidate biomarkers. Methods: BiomarkerBase, a biomarker knowledgebase developed by Amplion uses a comprehensive list of synonyms to identify biomarkers registered in the records of clinical trials via the government website clinicaltrials.gov. Under each of the registered breast cancer biomarkers (with the exceptions of HER2, ER, and PR), sub-searches were conducted for clinical trials that explicitly used TNBC (or the full name, triple negative breast cancer) in the title of the biomarkers’ studies. Of note, most trials in this review were completed phase II or III. The selected candidate biomarkers were classified into four FDA biomarker categories (surrogate, prognostic, predictive, or pharmacodynamic (PD)) as well as by location (blood/plasma, cell surface, cytoplasm, or nucleus). Current literature about the biomarkers was further examined using PubMed. There, we sought to find papers that studied how the biomarkers may interact. These markers were further organized into a “cellular protein network” that demonstrates potential connectivity. Results: Blood biomarkers include VEGF/VEGFR and IL-8; cell surface biomarkers include EGFR, IGFBP, c-Kit, c-Met, and PD-L1; cytoplasm biomarkers include PIK3CA/AKT/mTOR-related metabolites (GPC, PCh, Lactate/ glucose), pPKM2, F1,6BP, SPHK1, STAT1/IRF2BP2, S6, p4E-BP1, SUV39H1, PTEN, and ALDH1; and nucleus biomarkers include BRCA1, the glucocorticoid receptor (GR), TP53, and Ki67. Table 1 provides an overview of the examined surrogate, prognostic, predictive, and PD biomarkers in TNBC in addition to current literature found in PubMed that provides support for their potential use. Conclusion: To date, there are no clinically-validated biomarkers for TNBC, which has hindered the development of tailored therapy for both chemosensitive and refractory TNBC. Before validation and use of these biomarkers occurs, stringent-clinical criteria must be met first. The list and cellular protein network provided is an inventory and reference point for promising biomarkers for breakthrough, targeted therapies in TNBC. Citation Format: Brett A. Fleisher, Sihem Ait-Oudhia. A network based analysis for the treatment of triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5568A. doi:10.1158/1538-7445.AM2017-5568A
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
