Abstract P4-09-02: Concordance in fibroblast growth factor receptor 1 (FGFR1) and 2 (FGFR2) status in breast cancer during tumor progression

Abstract

Abstract BACKGROUND: In recent years, changes in HER2 and hormone receptor (HR) status between primary and metastatic breast cancer (BC) have been extensively reported. Additionally, current advances in BC biology have identified emerging biomarkers with clinical and prognostic implications, particularly the PI3K-AKT-mTOR and the FGF/FGFR pathways. FGFR1 and FGFR2 gene amplifications represent the most frequent genomic aberrations in BC. The 8p11-12 chromosomal region harboring the FGFR1 gene locus is amplified in about 10-18% of human BC, mainly in HR-positive/HER2-negative subtype, whereas the FGFR2 gene, located on chromosome 10q26, is amplified in approximately 4% of triple negative BC. To our knowledge, there is a lack of data regarding the concordance of FGFR1 and FGFR2 status between primary and metastatic tumors. METHODS: Tumor samples from 205 and 67 advanced BC patients diagnosed at our institution between 2010 and 2014 were screened for FGFR1 and FGFR2 amplification by FISH using the ZytoLight SPEC FGFR1/CEN8 and FGFR2/CEN10 probes, respectively. FGFR1 and FGFR2 amplification were defined as a ratio of FGFR1/CEN8 and FGFR2/CEN10 ≥ 2.2. We investigated the correlation of FGFR1 and FGFR2 status between primary and metastatic tumors in 16 and 13 patients, respectively, for whom paired samples were available. RESULTS: A total of 47 FGFR1-amplified patients (22.9%) and 3 FGFR2-amplified patients (4.5%) were identified. Patients with paired samples were classified according to FGFR1 and FGFR2 status in primary tumor. Regarding FGFR1 amplification, eight patients were FGFR1-amplified and eight were FGFR1-non-amplified. One patient in each group showed discordance in FGFR1 status in the metastatic tumor. Overall rate of concordance between primary and metastatic tumors was 87.5% (14/16). In relation to FGFR2 status, two patients were FGFR2-amplified and 11 were FGFR2-non-amplified with a 100% overall rate of concordance between paired samples (13/13). These data are summarized in Table 1. Table 1 Metastases PrimaryAmplifiedNon-amplifiedFGFR1Amplified (n=8)71 Non-amplified (n=8)17FGFR2Amplified (n=2)20 Non-amplified (n=11)011 CONCLUSIONS: Results suggest a high concordance in FGFR1 and FGFR2 status between primary and metastatic BC. The potential impact of these findings on the development of FGFR inhibitors merits further investigation. Citation Format: Zamora E, Aura C, Perez-Garcia J, Prudkin L, Meire A, Muñoz Cosuelo E, Jimenez J, Diaz-Delgado M, Ortega V, Soberino J, Farinas L, Salva F, Bellet M, Cruz C, Gomez P, Oliveira M, Vidal MJ, Saura C, Cortes J, Nuciforo P. Concordance in fibroblast growth factor receptor 1 (FGFR1) and 2 (FGFR2) status in breast cancer during tumor progression. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-09-02.