title: 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.
authors.affiliation: Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Tomiguchi
authors.affiliation: Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.|Department of Molecular-Targeting Therapy for Breast Cancer, Kumamoto University Hospital, Kumamoto, Japan.
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Yamamoto-Ibusuki
authors.affiliation: Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Lisa
authors.initials: L
authors.lastname: Goto-Yamaguchi
authors.affiliation: Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fujiki
authors.affiliation: Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Fujiwara
authors.affiliation: Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Sueta
authors.affiliation: Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Hayashi
authors.affiliation: Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Takeshita
authors.affiliation: Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Touko
authors.initials: T
authors.lastname: Inao
authors.affiliation: Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Iwase
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D018628:Gene Dosage / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000096:biosynthesis / Q000235:genetics*; D011960:Receptors, Estrogen / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D011960:Receptors, Estrogen; C508053:ERBB2 protein, human; C496348:FGFR1 protein, human
keywords: Biomarker; ER-positive/HER2-negative; breast cancer; fibroblast growth factor receptor-1; protein expression