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Department of Pathology, Josephine Nefkens Institute, Erasmus MC-University Medical Center Rotterdam, Room Be 432, PO Box 2040, 3000 CA Rotterdam, The Netherlands¹ Department of Medical Oncology, Josephine Nefkens Institute, Erasmus MC-University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands

(Correspondence should be addressed to L C J Dorssers; Email: l.dorssers{at}erasmusmc.nl)

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.

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				T. van Agthoven, A. M. Sieuwerts, M. E. Meijer-van Gelder, M. P. Look, M. Smid, J. Veldscholte, S. Sleijfer, J. A. Foekens, and L. C.J. Dorssers Relevance of Breast Cancer Antiestrogen Resistance Genes in Human Breast Cancer Progression and Tamoxifen Resistance J. Clin. Oncol., February 1, 2009; 27(4): 542 - 549. [Abstract] [Full Text] [PDF]