FGFR gene amplification and response to endocrine therapy in metastatic hormone receptor positive (HR+) breast cancer.

Abstract

1013 Background: Amplification in Fibroblast Growth Factor Receptor (FGFR) genes occurs in 10% of breast cancers, is associated with poor prognosis, and appears to drive resistance to endocrine therapies in vitro. However, the role of FGFR in modulating the clinical response to endocrine therapies is unclear, and could have important implications given that FGFR is a potential therapeutic target. This study aims to evaluate the association between FGFR amplification and clinical response to endocrine therapy in HR+ metastatic breast cancer (MBC). Methods: Primary or metastatic tumor specimens from patients with HR+/HER2 negative MBC underwent dual-color fluorescence in situ hybridization (FISH) of the FGFR1 locus on chromosome 8p. FISH ratios of ≥2 were considered positive for gene amplification (FGFR+). Time to progression (TTP) on first line endocrine therapy was evaluated in FGFR+ versus wild type (WT) patients using actuarial analysis. Results: Between 2012 and 2016, we identified 95 patients with HR+ MBC who underwent FGFR FISH testing. Of these, 24 (25.3%) were FGFR+. FGFR+ and WT patients did not differ in being postmenopausal at initial breast cancer diagnosis (28.6% vs. 31.7%; p = 1.0), having de-novo MBC (16.7% vs. 21.1%; p = 0.773), having received adjuvant chemotherapy (75% vs. 76.8%; p = 1.0) or having received adjuvant endocrine therapy (90% vs. 91.1%; p = 1.0). However, FGFR+ patients tended to be younger than WT patients (54.3 vs. 59.3 years; p = 0.045), and more likely to have PR-negative MBC (50.0% vs. 19.1%; p = 0.011). While there was no difference in TTP on first-line chemotherapy in FGFR+ vs. WT patients (5.0 vs. 6.2 months; p = 0.8), FGFR+ patients had a shorter median TTP on first-line endocrine therapy than WT (8.5 vs. 10.8 months; p = 0.047). These results were similar when stratified by presence of de-novo metastatic disease. Conclusions: In patients with HR+ MBC, FGFR gene amplification is associated with shorter time to progression on first line endocrine therapy. Further studies are needed to confirm these findings, and to investigate potential strategies for endocrine therapy and FGFR-directed combinatorial therapy in FGFR+ breast cancer.