title: The fibroblast growth factor receptor 1 (FGFR1), a marker of response to chemoradiotherapy in breast cancer?
abstract: The goal of the present study was to evaluate the role of the tyrosine kinase receptor fibroblast growth factor-1 (FGFR1) and its ligand, the fibroblast growth factor 2 (FGF2) in determining the response to chemoradiotherapy of breast cancers. S14 was a phase II neoadjuvant study carried out at the Institut Curie that recruited 59 patients between November 2001 and September 2003. This prospective study aimed to assess the pathological response after preoperative radiochemotherapy (5FU-Navelbine-radiotherapy) for large breast cancers. The expression of FGFR1 and FGF2 in tumor cells were assessed by immunohistochemistry. Tumors in which no staining was seen, were considered as negative for that protein. We used the Khi-2 test or the Fisher test to compare the qualitative variables and the Student t test or the non-parametric Wilcoxon test for the quantitative variables. We included in the present study all the 32 patients from the S14 cohort for whom the tissue blocks from the biopsy specimens were available with sufficient tumoral tissue. FGFR1 and FGF2 staining were observed respectively in 17 (56%) and 22 (68%) of the 32 tumoral biopsies. The expression of FGFR1 was associated with the hormone receptor positive status (p=0.0191). Only 11% (1/9) of the high grade tumors failed to respond to chemoradiotherapy compared to 68 % resistant tumors (15/22) among the low/intermediate grade tumors (p=0.0199). Among the low/intermediate grade tumors, FGFR1 negative tumors did not respond to chemoradiotherapy (0/9), compared with tumors expressing FGFR1 among which, almost one half had a good response (6/13) (p=0.0167). Among the low and intermediate grade breast cancers, the FGFR1 negative tumors were resistant to chemoradiotherapy. The expression of FGFR1 in patients' biopsies may serve as a marker of response to chemoradiotherapy.
authors.affiliation: Department of Radiation Oncology, Institut Curie, 26 rue d'Ulm, Paris, 75005, France. massabeau.carole@claudiusregaud.fr
authors.forename: Carole
authors.initials: C
authors.lastname: Massabeau
authors.forename: Brigitte
authors.initials: B
authors.lastname: Sigal-Zafrani
authors.forename: Lisa
authors.initials: L
authors.lastname: Belin
authors.forename: Alexia
authors.initials: A
authors.lastname: Savignoni
authors.forename: Marion
authors.initials: M
authors.lastname: Richardson
authors.forename: Youlia M
authors.initials: YM
authors.lastname: Kirova
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Cohen-Jonathan-Moyal
authors.forename: Frédérique
authors.initials: F
authors.lastname: Mégnin-Chanet
authors.forename: Janet
authors.initials: J
authors.lastname: Hall
authors.forename: Alain
authors.initials: A
authors.lastname: Fourquet
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D018275:Carcinoma, Lobular / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D059248:Chemoradiotherapy; D017322:Clinical Trials, Phase II as Topic; D019008:Drug Resistance, Neoplasm; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D011836:Radiation Tolerance; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism*; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D014408:Biomarkers, Tumor; D016222:Fibroblast Growth Factor 2; D014747:Vinblastine; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1; D000077235:Vinorelbine; D005472:Fluorouracil