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


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.
Department of Internal Medicine, Yonsei Cancer Center, Seoul, Korea.
H
H
Chang
S Y
SY
Rha
H-C
HC
Jeung
C-K
CK
Im
J B
JB
Ahn
W S
WS
Kwon
N C
NC
Yoo
J K
JK
Roh
H C
HC
Chung
D064286:ATP Binding Cassette Transporter 1; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D000368:Aged; D000483:Alleles; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D016019:Survival Analysis; D016896:Treatment Outcome
D064286:ATP Binding Cassette Transporter 1; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; D017239:Paclitaxel