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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
Combined HER3-EGFR score in triple-negative breast cancer provides prognostic and predictive significance superior to individual biomarkers
Scientific Reports, Volume 10, No. 1, Article 3009, Year 2020
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Description
Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 3 (HER3) have been investigated as triple-negative breast cancer (TNBC) biomarkers. Reduced EGFR levels can be compensated by increases in HER3; thus, assaying EGFR and HER3 together may improve prognostic value. In a multi-institutional cohort of 510 TNBC patients, we analyzed the impact of HER3, EGFR, or combined HER3-EGFR protein expression in pre-treatment samples on breast cancer-specific and distant metastasis-free survival (BCSS and DMFS, respectively). A subset of 60 TNBC samples were RNA-sequenced using massive parallel sequencing. The combined HER3-EGFR score outperformed individual HER3 and EGFR scores, with high HER3-EGFR score independently predicting worse BCSS (Hazard Ratio [HR] = 2.30, p = 0.006) and DMFS (HR = 1.78, p = 0.041, respectively). TNBCs with high HER3-EGFR scores exhibited significantly suppressed ATM signaling and differential expression of a network predicted to be controlled by low TXN activity, resulting in activation of EGFR, PARP1, and caspases and inhibition of p53 and NFκB. Nuclear PARP1 protein levels were higher in HER3-EGFR-high TNBCs based on immunohistochemistry (p = 0.036). Assessing HER3 and EGFR protein expression in combination may identify which adjuvant chemotherapy-treated TNBC patients have a higher risk of treatment resistance and may benefit from a dual HER3-EGFR inhibitor and a PARP1 inhibitor. © 2020, The Author(s).
Authors & Co-Authors
Ogden, Angela
United States, Atlanta
Georgia State University
Bhattarai, Shristi
United States, Atlanta
Georgia State University
Mongan, Nigel Patrick
United Kingdom, Nottingham
University of Nottingham
United States, New York
Weill Cornell Medicine
Alsaleem, Mansour A.
United Kingdom, Nottingham
University of Nottingham
Green, Andew R.
United Kingdom, Nottingham
University of Nottingham
Aleskandarany, Mohammed A.
United Kingdom, Nottingham
University of Nottingham
Ellis, Ian O.
United Kingdom, Nottingham
University of Nottingham
Krishnamurti, Uma
United States, Atlanta
Emory University School of Medicine
Janssen, Emiel Adrianus Maria
Norway, Stavanger
Stavanger Universitetssjukehus
Norway, Stavanger
Universitetet I Stavanger
Rakha, Emad A.
United Kingdom, Nottingham
University of Nottingham
Rida, Padmashree C.G.
Unknown Affiliation
Aneja, Ritu
United States, Atlanta
Georgia State University
Statistics
Citations: 23
Authors: 12
Affiliations: 6
Identifiers
Doi:
10.1038/s41598-020-59514-1
ISSN:
20452322
Research Areas
Cancer
Environmental
Study Design
Cohort Study