Exploratory analysis of candidate germline gene polymorphisms in breast cancer patients treated with neoadjuvant anthracycline-containing chemotherapy and associations with febrile neutropenia.
OBJECTIVE
SNPs may be associated with (side) effects of chemotherapy and may be useful as biomarkers to predict febrile neutropenia.


METHODS
187 DNA samples extracted from formalin-fixed paraffin-embedded tissue from patients with stage II/III HER2-negative breast cancer were genotyped.


RESULTS
Candidate SNPs were selected and explored for association with febrile neutropenia and/or pathological complete response. TT genotype of 388 C>T in FGFR4 (rs351855) had a tendency toward higher incidence of febrile neutropenia during neoadjuvant chemotherapy, compared with the CT (p = 0.383) genotype and compared with the CC genotype (p = 0.068).


CONCLUSIONS
The TT genotype of 388 C>T FGFR4 may be related to incidence of febrile neutropenia during neoadjuvant TAC (docetaxel, doxorubicin, cyclophosphamide) chemotherapy and is possibly useful as a patient-related risk factor when assessing febrile neutropenia risk. Original submitted 23 January 2015; Revision submitted 26 May 2015.
Department of Medical Oncology, Leiden University Medical Center, PO Box 9600, Albinusdreef 2, 2300 RC Leiden, The Netherlands.|Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
A
A
Charehbili
Department of Medical Oncology, Leiden University Medical Center, PO Box 9600, Albinusdreef 2, 2300 RC Leiden, The Netherlands.
S
S
de Groot
Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
T
T
van der Straaten
Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
J J
JJ
Swen
Department of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands.
H
H
Pijl
Department of Medical Oncology, Leiden University Medical Center, PO Box 9600, Albinusdreef 2, 2300 RC Leiden, The Netherlands.
H
H
Gelderblom
Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
C J H
CJ
van de Velde
Department of Medical Oncology, Leiden University Medical Center, PO Box 9600, Albinusdreef 2, 2300 RC Leiden, The Netherlands.
J W R
JW
Nortier
Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
H J
HJ
Guchelaar
Department of Medical Oncology, Leiden University Medical Center, PO Box 9600, Albinusdreef 2, 2300 RC Leiden, The Netherlands.
J R
JR
Kroep
D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000009:adverse effects* / Q000627:therapeutic use*; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D064147:Febrile Neutropenia / Q000139:chemically induced* / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005838:Genotype; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic
SNPs; breast cancer; febrile neutropenia; neoadjuvant; pCR; polymorphisms