Fibroblast growth factor receptor‐1 protein expression is associated with prognosis in estrogen receptor‐positive/human epidermal growth factor receptor‐2‐negative primary breast cancer

Abstract

Recently, research into the development of new targeted therapies has focused on specific genetic alterations to create advanced, more personalized treatment. One of the target genes, fibroblast growth factor receptor‐1 (FGFR1), has been reported to be amplified in estrogen receptor (ER)‐positive subtype breast cancer, and is considered one possible mechanism of endocrine resistance through cross‐talk between ER and growth factor receptor signaling. We performed a comprehensive analysis of FGFR1 at the levels of gene copy number, transcript and protein expression, and examined the relationships between FGFR1 status and clinicopathological parameters, including prognosis in 307 ER‐positive/HER2‐negative primary breast cancer patients treated with standard care at our institute. Most notably, a high level of FGFR1 protein expression was observed in 85 patients (27.7%), and was positively associated with invasive tumor size (P = 0.039). Furthermore, univariate analysis revealed that high FGFR1 protein expression was significantly correlated with poor relapse‐free survival rate (P = 0.0019, HR: 2.63, 95% confidence interval: 1.17–5.98), and showed a tendency towards an increase in recurrent events if the observation period extended beyond the 5 years of the standard endocrine treatment term. FGFR1 gain/amplification was found in 43 (14.0%) patients, which was only associated with higher nuclear grade (P = 0.010). No correlation was found between FGFR1 mRNA expression levels and any clinicopathological factors. Overall, the level of FGFR1 protein expression may be a biomarker of ER‐positive/HER2‐negative primary breast cancer with possible resistance to standard treatment, and may be a useful tool to identify more specific patients who would benefit from FGFR‐1 targeted therapy.

Effects of FGFR1 Gene Polymorphisms on the Risk of Breast Cancer and FGFR1 Protein Expression

“…Another research carried out by Elsheikh et al also concluded that FGFR1 amplification was an independent predictor of breast cancer prognosis [9]. Our study showed that high FGFR1 protein expression was significantly associated with poor outcome [9,10,24,25], and a number of studies have demonstrated that ER+ / FGFR1-amplified breast cancer cells and tumors retain proliferation and ERα genomic activity despite estrogen deprivation therapy. It is reported that one third of FGFR1-amplified tumors also harbor amplification of CCND1, FGF3, FGF4, and FGF19 [26].…”

A New Genetic Risk Score to Predict the Outcome of Locally Advanced or Metastatic Breast Cancer Patients Treated With First-Line Exemestane: Results From a Prospective Study

“…Previous reports indicate that endocrine resistance involves a cross-talk between growth factor pathways and estrogen signaling. 9,36 In BC, aberrant FGFR signaling, including the FGFR4-rs351855 polymorphism (Gly388Arg), has been involved in tumor progression and resistance to tamoxifen. 37 In vitro reports showed an increased motility of mammary cells with 388 Arg/Arg variant and also an increased extracellular matrix degradation.…”

A unifying biology of sex steroid-induced apoptosis in prostate and breast cancers

“…Most mutations occur in positions Y537 and D538 and are described as gain-of-function mutations, which lead to constitutive ligand-independent activation of the ER ( Robinson et al . 2013 , Toy et al . 2013 ).…”