Side effects after docetaxel treatment in Taiwanese breast cancer patients with CYP3A4, CYP3A5, and ABCB1 gene polymorphisms

Clin Chim Acta. 2009 Jun 27;404(2):160-5. doi: 10.1016/j.cca.2009.03.038. Epub 2009 Mar 28.


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.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • Adult
  • Alleles
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Cyclophosphamide / therapeutic use
  • Cytochrome P-450 CYP3A / genetics*
  • Docetaxel
  • Etoposide / administration & dosage
  • Etoposide / adverse effects
  • Etoposide / therapeutic use
  • Female
  • Genotype
  • Humans
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Receptor, ErbB-2 / analysis
  • Receptors, Estrogen / analysis
  • Receptors, Progesterone / analysis
  • Taxoids / administration & dosage
  • Taxoids / adverse effects*
  • Taxoids / therapeutic use


  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Taxoids
  • Docetaxel
  • Etoposide
  • Cyclophosphamide
  • CYP3A5 protein, human
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • Receptor, ErbB-2

Supplementary concepts

  • TEC protocol