Side effects after docetaxel treatment in Taiwanese breast cancer patients with CYP3A4, CYP3A5, and ABCB1 gene polymorphisms.
BACKGROUND
Breast cancer patients initiating TEC (including docetaxel, epirubicin, and cyclophosphamide) treatment were genotyped for CYP3A4, CYP3A5, and ABCB1 to identify variability factors of side effects for docetaxel.


METHODS
The planned dose of docetaxel per course was formulated according to each patient's height and weight. Each participant had received TEC treatment for 6 consecutive cycles. The single nucleotide polymorphisms (SNPs) of CYP3A4*4 (352A > G), CYP3A4*5 (653C > G), and CYP3A4*18A (20070T > C) for the CYP3A4 gene, CYP3A5*3A (6986A > G) for the CYP3A5 gene, and -41A > G, -145C > G, 1236C > T, 2677G > T(A), and 3435C > T SNPs for the ABCB1 gene were determined by using the restriction fragment length polymorphism of polymerase chain reaction products and the restriction enzymes.


RESULTS
Fifty-nine Taiwanese women (mean age, 46 y; range, 30-64 y) treated for breast cancer with TEC were recruited. We found that patients carrying the CYP3A5*1/*3 genotype demonstrated more side effects of fever, pleural effusion, and febrile neutropenia than those with the CYP3A5*3/*3 genotype (p = 0.075, 0.077, and 0.030, respectively); moreover, patients with the ABCB1 2677G/G genotype also showed more side effects of fever and febrile neutropenia than those with other genotypes (p = 0.024 and 0.027), In regard to ABCB1 3435C>T, patients with ABCB1 3435C/C tended to suffer leucopenia (p = 0.057).


CONCLUSIONS
There could be correlations between certain side effects of docetaxel treatment and polymorphisms of these metabolic enzymes. Unfortunately, there is not so much evidence due to the small sample size of this study which restricts the statistical power.
Tsai
Shih-Meng
SM
Department of Public Healthy, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Lin
Chiou-Ya
CY
Wu
Szu-Hsien
SH
Hou
Linda Ann
LA
Ma
Hsu
H
Tsai
Li-Yu
LY
Hou
Ming-Feng
MF