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Annals of Oncology Advance Access originally published online on October 3, 2008
Annals of Oncology 2009 20(2):272-277; doi:10.1093/annonc/mdn624
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© The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

breast cancer

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

H. Chang1,2,3, S. Y. Rha1,2,3,4, H. -C. Jeung1,2,3, C. -K. Im1,2,3, J. B. Ahn1,2,3, W. S. Kwon2,4, N. C. Yoo1,2,3, J. K. Roh1,2,3,4 and H. C. Chung1,2,3,4,*

1 Department of Internal Medicine
2 Cancer Metastasis Research Center
3 Medical Oncology, Yonsei Cancer Center
4 Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea

* Correspondence to: Dr H. C. Chung, Medical Oncology, Yonsei Cancer Center, Cancer Metastasis Research Center, Department of Internal Medicine, Yonsei University College of Medicine, 134, Shinchon-Dong, Seodaemoon-gu, 120-752, Seoul, Korea. Tel: +82-2-2228-8132; Fax: +82-2-393-3652; E-mail: unchung8{at}yuhs.ac

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/m2 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.

Key words: ABCB1 polymorphism, breast neoplasms, paclitaxel, tumor response

Received for publication June 13, 2008. Revision received August 6, 2008. Accepted for publication August 6, 2008.


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