Impact of fibroblast growth factor receptor 1 (FGFR1) amplification on the prognosis of breast cancer patients

Abstract

Purpose Various aberrations in the fibroblast growth factor receptor genes FGFR1, FGFR2, and FGFR3 are found in different cancers, including breast cancer (BC). This study analyzed the impact of FGFR amplification on the BC prognosis. Methods The study included 894 BC patients. The amplification rates of FGFR1, FGFR2, and FGFR3 were evaluated on tissue microarrays using fluorescence in situ hybridization (FISH). Associations between these parameters and prognosis were analyzed using multivariate Cox regression analyses. Results FGFR1 FISH was assessable in 503 samples, FGFR2 FISH in 447, and FGFR3 FISH in 562. The FGFR1 amplification rate was 6.6% (n = 33). Increased FGFR2 copy numbers were seen in 0.9% (n = 4); only one patient had FGFR3 amplification (0.2%). Most patients with FGFR1 amplification had luminal B-like tumors (69.7%, n = 23); only 32.6% (n = 153) of patients without FGFR1 amplification had luminal B-like BC. Other patient and tumor characteristics appeared similar between these two groups. Observed outcome differences between BC patients with and without FGFR1 amplification did not achieve statistical significance; however, there was a trend toward poorer distant metastasis-free survival in BC patients with FGFR1 amplification (HR = 2.08; 95% CI 0.98 to 4.39, P = 0.05). Conclusion FGFR1 amplification occurs most frequently in patients with luminal B-like BC. The study showed a nonsignificant correlation with the prognosis, probably due to the small sample size. Further research is therefore needed to address the role of FGFR1 amplifications in early BC patients. FGFR2 and FGFR3 amplifications are rare in patients with primary BC.

Gene Mutations Associated With Clinical Characteristics in the Tumors of Patients With Breast Cancer

“…ZNF703 was found a common luminal B breast cancer oncogene ( 27 ). FGFR1 amplification was positively associated with luminal B breast cancer ( 28 ). In this work, FGFR1 mutations were either amplification (83.3%) or gene fusion (16.7%).…”

PNSA, a Novel C-Terminal Inhibitor of HSP90, Reverses Epithelial–Mesenchymal Transition and Suppresses Metastasis of Breast Cancer Cells In Vitro

“…EGFR frequent overexpression and/or hyperactivation in breast carcinomas play an active role in facilitating brain-specific metastatic spread [ 49 , 50 ]. In addition, FGFR aberrations increase the risk of brain metastases and predict poor prognosis in metastatic breast cancer patients [ 51 , 52 ]. We found that PNSA distinctly suppressed the protein levels of EGFR and FGFR, and subsequently inhibiting down-streaming signaling pathway with reduction of P-ERK, P-STAT3, and P-AKT.…”

Expression of the Immunohistochemical Markers CK5, CD117, and EGFR in Molecular Subtypes of Breast Cancer Correlated with Prognosis

“…As previously described, corresponding tissue microarrays (TMAs) were created for all patients in the BBCC cohort for whom paraffin blocks were available [29]. As part of the initial documentation of the disease, the tumor status was documented in accordance with the TNM classification.…”