Abstract 121: The EGFR gatekeeper mutation T790M is present in selected patients with early breast cancer

Abstract

Abstract Introduction. The epidermal growth factor receptor (EGFR) is one of the major oncogenes in a variety of human cancers including breast cancer (BC). While EGFR overexpression and/or amplification has been shown to occur frequently in human breast cancer, EGFR-activating mutations are suggested to be rare if not absent. Thus, the aim of our study was to examine the presence of somatic EGFR gene mutations in a group of norwegian patients diagnosed with early breast cancer. Patients. We investigated tumor biopsies obtained from 132 patients with early breast cancer treated at the Akershus University Hospital (University of Oslo) in 2007/2008. The majority of patients (n = 82) belonged to the luminal- A/B subtypes of BC. In addition, 33 patients were classified as HER-2 positive patients (IHC 3+ or amplification verified by FISH) and 17 as triple-negative breast cancer (TNBC) patients. Methods. Briefly, DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tumor tissue using QIAsymphony DSP DNA Mini Kit (Qiagen Inc.). The extraction of DNA was performed by fully automated purification using the QIAsymphony SP/AS system. EGFR-mutations were detected using a Therascreen EGFR RGQ PCR kit according to the manufacturer´s protocol. We tested for point mutations in exon 18 (G719A/C/S), in-frame deletions in exon 19 (ΔE746-A750), in-frame insertions as well as point mutations in exon 20 (S768I, T790M) and a point mutation in exon 21 (L858R). Results. In the present study we detected three individuals with an EGFR-T790M mutation. Two of the patients were diagnosed with TNBC, while the disease of the third patient was classified as a luminal-A type breast cancer. Interestingly, the T790M-mutation was present in the biopsies obtained during surgery before adjuvant therapy was initiated. No anti-cancer therapy has been given prior to surgery. According to our best knowledge, the T790M-”TKI-resistance-mutation” has not been detected in early breast cancer previously. This finding contrasts the observations made in lung cancer patients where the T790M mutation in general is a classical second mutation causing drug resistance during ongoing TKI-therapy. No other EGFR-mutations were detected in our patients. Conclusion: To our best knowledge we provide first evidence for the presence of the EGFR-T790M-mutation in human early breast cancer. Thus, treatment with novel EGFR-targeting cancer drugs (like “pan-HER-inhibitors”) affecting also T790M-mutated-EGFR may be worthwhile to be tested in highly selected breast cancer patients. Citation Format: Vahid Bemanian, Torill Sauer, Joel Touma, Bjørn A. Lindstedt, Ying Chen, Hilde P. Ødegård, Ida R. Bukholm, Jürgen Geisler. The EGFR gatekeeper mutation T790M is present in selected patients with early breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 121. doi:10.1158/1538-7445.AM2015-121