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.
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 cancerpatients treated with chemotherapy. We evaluated the association between clinical outcome (safety and efficacy) of paclitaxel monotherapy in metastatic breast cancerpatients 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 cancerpatients.
Authors: Maryam B Lustberg; Shubham Pant; Amy S Ruppert; Tong Shen; Yong Wei; Ling Chen; Lisa Brenner; Donna Shiels; Rhonda R Jensen; Michael Berger; Ewa Mrozek; Bhuvaneswari Ramaswamy; Michael Grever; Jessie L Au; M Guillaume Wientjes; Charles L Shapiro Journal: Cancer Chemother Pharmacol Date: 2012-05-22 Impact factor: 3.333
Authors: Eneida Turiján-Espinoza; Víctor Manuel Ruíz-Rodríguez; Edith Elena Uresti-Rivera; Ernesto Martínez-Leija; José de Jesús Zermeño-Nava; Arturo Guel-Pañola; Silvia Romano-Moreno; Juan Manuel Vargas-Morales; Diana Patricia Portales-Pérez Journal: Cancer Chemother Pharmacol Date: 2021-03-19 Impact factor: 3.333
Authors: A B D'Assoro; T Liu; C Quatraro; A Amato; M Opyrchal; A Leontovich; Y Ikeda; S Ohmine; W Lingle; V Suman; J Ecsedy; I Iankov; A Di Leonardo; J Ayers-Inglers; A Degnim; D Billadeau; J McCubrey; J Ingle; J L Salisbury; E Galanis Journal: Oncogene Date: 2013-01-21 Impact factor: 9.867