Fibroblast growth factor receptor 4 predicts failure on tamoxifen therapy in patients with recurrent breast cancer.

Abstract

Tamoxifen treatment of estrogen-dependent breast cancer ultimately loses its effectiveness due to the development of resistance. From a functional screen for identifying genes responsible for tamoxifen resistance in human ZR-75-1 breast cancer cells, fibroblast growth factor (FGF) 17 was recovered. The aim of this exploratory study was to assess the predictive value of FGF17 and the receptors FGFR1-4 for the type of response to tamoxifen treatment (clinical benefit) and the duration of progression-free survival (PFS) in patients with recurrent breast cancer. mRNA levels of FGF17 and FGFR1-4 were quantified by real-time reverse transcriptase PCR in 285 estrogen receptor-positive breast carcinomas with clinical follow-up. All patients had recurrent disease and were treated with tamoxifen as first-line systemic therapy for local or distant relapse. FGF17 and FGFR1-3 mRNA levels had no significant predictive value for this group of patients. However, high FGFR4 mRNA levels analyzed as a continuous log-transformed variable predicted poor clinical benefit (odds ratio=1.22; P=0.009) and shorter PFS (hazard ratio=1.18; P<0.001). In addition, in multivariable analysis, the predictive value of FGFR4 was independent from the traditional predictive factors. Our analyses show that FGFR4 may play a role in the biological response of the tumor to tamoxifen treatment. In addition, as altered expression of FGF17 causes tamoxifen resistance in vitro, the FGF signaling pathway could be a valuable target in the treatment of breast cancer patients resistant to endocrine treatment.

• Authors: Danielle Meijer, Anieta M Sieuwerts, Maxime P Look, Ton van Agthoven, John A Foekens, Lambert C J Dorssers
• Journal: Endocrine-related cancer (Endocr Relat Cancer) Vol. 15 Issue 1 Pg. 101-11 (Mar 2008) ISSN: 1351-0088 [Print] England
• PMID: 18310279 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Hormonal
• FGF17 protein, human
• RNA, Messenger
• Receptors, Estrogen
• Receptors, Progesterone
• Tamoxifen
• Fibroblast Growth Factors
• FGFR2 protein, human
• FGFR3 protein, human
• Receptor, Fibroblast Growth Factor, Type 2
• Receptor, Fibroblast Growth Factor, Type 3
• Receptor, Fibroblast Growth Factor, Type 4

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents, Hormonal (therapeutic use)
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Female
• Fibroblast Growth Factors (genetics, metabolism)
• Humans
• Lymph Nodes (pathology)
• Lymphatic Metastasis
• Middle Aged
• Neoplasm Recurrence, Local (diagnosis, drug therapy)
• Prognosis
• RNA, Messenger (genetics, metabolism)
• Receptor, Fibroblast Growth Factor, Type 2 (genetics, metabolism)
• Receptor, Fibroblast Growth Factor, Type 3 (genetics, metabolism)
• Receptor, Fibroblast Growth Factor, Type 4 (genetics, metabolism)
• Receptors, Estrogen (metabolism)
• Receptors, Progesterone (metabolism)
• Retrospective Studies
• Reverse Transcriptase Polymerase Chain Reaction
• Skin Neoplasms (drug therapy, metabolism, secondary)
• Survival Rate
• Tamoxifen (therapeutic use)
• Treatment Failure