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Association of the ABCB1 gene polymorphisms 2677G>T/A and 3435C>T with clinical outcomes of paclitaxel monotherapy in metastatic breast cancer patients

 H. Chang  ;  S. Y. Rha  ;  H.-C. Jeung  ;  C.-K. Im  ;  J. B. Ahn  ;  W. S. Kwon  ;  N. C. Yoo  ;  J. K. Roh  ;  H. C. Chung 
 ANNALS OF ONCOLOGY, Vol.20(2) : 272-277, 2009 
Journal Title
Issue Date
ATP Binding Cassette Transporter 1 ; ATP-Binding Cassette Transporters/genetics* ; ATP-Binding Cassette, Sub-Family B, Member 1/genetics ; Adult ; Aged ; Alleles ; Antineoplastic Agents, Phytogenic/administration & dosage ; Antineoplastic Agents, Phytogenic/therapeutic use* ; Breast Neoplasms/drug therapy* ; Breast Neoplasms/genetics* ; Breast Neoplasms/pathology ; DNA, Neoplasm/genetics ; DNA, Neoplasm/isolation & purification ; Disease Progression ; Dose-Response Relationship, Drug ; Drug Resistance, Neoplasm/genetics ; Female ; Gene Frequency ; Genotype ; Haplotypes ; Homozygote ; Humans ; Middle Aged ; Neoplasm Metastasis ; Paclitaxel/administration & dosage ; Paclitaxel/therapeutic use* ; Polymorphism, Genetic ; Regression Analysis ; Survival Analysis ; Treatment Outcome
BACKGROUND: ABCB1 is responsible for multidrug resistance, the principal mechanism by which many cancers develop resistance to chemotherapeutic drugs. There is a controversy whether ABCB1 gene polymorphisms correlate with survival and response in cancer patients treated with chemotherapy. We evaluated the association between clinical outcome (safety and efficacy) of paclitaxel monotherapy in metastatic breast cancer patients with ABCB1 gene polymorphisms 2677G>T/A or 3435C>T.

PATIENTS AND METHODS: Patients with metastatic breast cancer were treated with 175 mg/m(2) paclitaxel per 3-week cycle. Peripheral blood mononuclear cells from patients were used to genotype ABCB1 2677G>T/A and 3435C>T polymorphisms. Genotypes were investigated for their association with tumor response, survival, toxicity, and chemoresistance.

RESULTS: ABCB1 3435 CT showed a significantly lower disease control rate than the CC genotype (P = 0.025). ABCB1 3435 CT was correlated with shorter overall survival (OS) in Cox regression analysis (P = 0.026). The 2677 GG genotype showed a significant association with chemoresistance to paclitaxel and anthracycline (P = 0.04 and 0.04, respectively). None of the ABCB1 genotypes correlated with toxicity.

CONCLUSIONS: ABCB1 genotypes may be a predictor of paclitaxel activity as well as a prognostic factor in metastatic breast cancer patients
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Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kwon, Woo Sun(권우선) ORCID logo https://orcid.org/0000-0003-0268-5624
Roh, Jae Kyung(노재경)
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Ahn, Joong Bae(안중배) ORCID logo https://orcid.org/0000-0001-6787-1503
Yoo, Nae Choon(유내춘)
Im, Chong Kun(임종근)
Chang, Hyun(장현)
Chung, Hyun Cheol(정현철) ORCID logo https://orcid.org/0000-0002-0920-9471
Jeung, Hei Cheul(정희철) ORCID logo https://orcid.org/0000-0003-0952-3679
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