Abstract B63: Prognostic and predictive value of EGFR and EGFR-ligands in blood of breast cancer patients: A systematic review

The epidermal growth factor receptor (EGFR) and its ligands are involved in breast cancer pathogenesis and serve as co-targets for dual- and pan-EGFR-inhibitors in breast cancer treatment. There are indications that EGFR and EGFR-ligands are involved in resistance towards certain breast cancer treatments, including trastuzumab and antiendocrine treatment. The aim of the systematic review is to explore the validity of EGFR and EGFR-ligands in blood as prognostic and predictive biomarkers in breast cancer. The systematic review is conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) 2015 Statement. Literature searches were conducted in PubMed, Embase, and Cochrane Library to identify publications exploring correlations between levels of EGFR or EGFR-ligands in serum or plasma of breast cancer patients and prognostic or predictive outcome measures. A total of 2152 publications were identified and assessed for eligibility through title screening, followed by abstract screening and eventually assessment of full-text reports. A total of 16 publications were eligible for inclusion, of which 12 studies evaluated EGFR in serum and 5 studies evaluated one or more of the EGFR-ligands in serum. Current evidence indicates associations between low baseline serum-EGFR and shorter survival or reduced response to treatment in patients with advanced or metastatic breast cancer, especially in patients with estrogen and/or progesterone receptor-positive tumors. Though several studies did not find the same significant trends, none of the identified studies reported opposing results. Regarding EGFR-ligands, the prognostic and predictive value of S-Amphiregulin (S-AREG), S-Epidermal Growth Factor (S-EGF), and S-Transforming Growth Factor-α (S-TGFα) in breast cancer has been investigated in several studies, whereas no studies evaluated S-Betacellulin, S-Heparin Binding Epidermal Growth factor, S-Epiregulin, or S-Epigen. Most of the studies evaluating S-AREG, S-EGF, or S-TGFα included few patients and all studies were performed on patients experiencing HER2-positive advanced breast cancer (in one study HER2-status was not reported). Only one larger study was identified. In this study no associations between S-AREG, S-EGF, or S-TGFα and progression-free survival were observed in patients receiving either pertuzumab+trastuzumab+docetaxel or placebo+trastuzumab+docetaxel. However, decreases or increases in tumor marker levels were not evaluated in this study. The utility of both S-EGFR and serum levels of EGFR-ligands as predictive and prognostic markers in breast cancer has only been investigated in highly selected subsets of breast cancer patients, so extensive aspects remain to be uncovered. Based on the current knowledge, it is not possible to make recommendations either for or against clinical application. Large, well-planned studies are needed in order to clarify and validate the clinical impact of EGFR and EGFR-ligands in the clinical management of breast cancer patients. Citation Format: Ina Mathilde Kjaer, Troels Bechmann, Ivan Brandslund, Jonna Skov Madsen. Prognostic and predictive value of EGFR and EGFR-ligands in blood of breast cancer patients: A systematic review [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr B63.