FGFR4 Arg388 genotype is associated with pathological complete response to neoadjuvant chemotherapy for primary breast cancer.
BACKGROUND
A single-nucleotide polymorphism (SNP) in the FGFR4 gene is associated with poor prognosis in solid tumors. A recent study presented the first evidence that FGFR4 Arg388 could predict resistance to adjuvant chemotherapy in breast cancer. The present study evaluates the potential of this SNP to predict response to neoadjuvant chemotherapy (NCT) for primary breast cancer (PBC).


METHODS
As part of a randomized phase II trial, 257 patients received either doxorubicin-cyclophosphamide (AC) or doxorubicin-pemetrexed (AP) followed by docetaxel (Doc; Taxotere) as NCT for T2-4/N0-2/M0 PBC. FGFR4 genotype analyzed on germline DNA was correlated with clinicopathologic variables, clinical response, and pathological complete response (pCR) using univariate and multivariate analyses.


RESULTS
Only axillary lymph node status was associated with FGFR4 Arg388 [odds ratio (OR) 1.82, P = 0.03]. Joint analysis of both treatment arms revealed a correlation of FGFR4 Arg388 with clinical response (OR 2.14, P = 0.03) but not with pCR. In the AC-Doc arm, however, FGFR4 Arg388 was a strong predictor of pCR in the multivariate analysis (OR 3.79, P = 0.03). A significant interaction between FGFR4 genotype and treatment (P = 0.01) was found, indicating a therapy-specific effect.


CONCLUSIONS
We provide the evidence that FGFR4 388Arg is an independent predictor of pCR following AC-Doc as NCT in PBC.
Marmé
F
F
Department of Obstetrics and Gynecology, University Hospital Heidelberg; Department of Molecular Genetics. Electronic address: Frederik.Marme@med.uni-heidelberg.de.
Werft
W
W
Department of Biostatistics.
Benner
A
A
Department of Biostatistics.
Burwinkel
B
B
Department of Obstetrics and Gynecology, University Hospital Heidelberg; Department of Molecular Epidemiology, German Cancer Research Center.
Sinn
P
P
Institute of Pathology, University of Heidelberg, Heidelberg, Germany.
Sohn
C
C
Department of Obstetrics and Gynecology, University Hospital Heidelberg.
Lichter
P
P
Department of Molecular Genetics.
Hahn
M
M
Department of Molecular Genetics.
Schneeweiss
A
A
Department of Obstetrics and Gynecology, University Hospital Heidelberg.
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001120:Arginine / Q000737:chemistry / Q000235:genetics*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D017931:DNA Primers; D005260:Female; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011379:Prognosis; D051499:Receptor, Fibroblast Growth Factor, Type 4 / Q000737:chemistry / Q000235:genetics*; D012074:Remission Induction
D017931:DNA Primers; D001120:Arginine; C496371:FGFR4 protein, human; D051499:Receptor, Fibroblast Growth Factor, Type 4