Abstract P4-09-01: FGFR1 protein expression is associated with prognosis in primary breast cancer: A comprehensive analysis of gene copy number, mRNA and protein expression

Abstract

Abstract Background: The Cancer Genome Atlas (TCGA) showed that copy number gain/amplification of FGFR1 was around 10% in primary breast cancer. FGFR1 gene amplification in breast cancer has been reported in some studies, more likely seen in ER-positive subtype. Several preclinical and clinical studies demonstrated that FGFR1 was one of novel targets of therapy for metastatic breast cancer. Previous studies suggested that aberrant FGFR1 expression was associated with poor prognosis, while there was no report that compared copy number aberration, mRNA and protein expression. The aim of this study is to analyze FGFR1 gene copy number, expression levels of FGFR1 mRNA and FGFR1 protein in ER-positive/HER2-negative primary breast cancer, and to examine the relationship between FGFR1 status and clinicopathological parameters including prognosis. Methods: The cohort of this study included 307 ER-positive/HER2-negative primary invasive breast cancer patients treated with standard care at Kumamoto University Hospital between June 2000 and January 2011. We performed a comprehensive analysis of FGFR1 at the levels of gene copy number, mRNA and FGFR1 protein expression analyzed by qPCR, qRT-PCR and immunohistochemistry, respectively. Results: FGFR1 gain/amplification was identified in 43 (14.0%) out of 307 patients. FGFR1 gain/amplification had significantly associated with higher nuclear grade (p=0.010). No correlations between FGFR1 mRNA expression levels and any clinicopathological factors were found. Expression levels of FGFR1 protein was positively associated with invasive tumor size (p=0.039). Modest positive correlations between these three (FGFR1 gene gain/amplification, expression levels of FGFR1 mRNA and FGFR1 protein) were found. The univariate analysis revealed that high FGFR1 protein expression was significantly related to poor prognosis (p=0.0019, HR: 2.63, 95%CI: 1.17-5.98) in terms of relapse-free survival (RFS) but not breast cancer-specific survival. The univariate analysis did not show that any factors except FGFR1 protein expression were significantly associated with RFS in this cohort. Conclusion: Expression levels of FGFR1 protein may be an independent prognostic factor in terms of RFS for ER-positive/HER2-negative breast cancer patients receiving standard care. Citation Format: Tomiguchi M, Yamamoto Y, Yamamoto-Ibusuki M, Yamaguchi R, Fujiki Y, Fujiwara S, Sueta A, Takeshita T, Inao T, Iwase H. FGFR1 protein expression is associated with prognosis in primary breast cancer: A comprehensive analysis of gene copy number, mRNA and protein expression. [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 P4-09-01.