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Impact of genetic variability and treatment-related factors on outcome in early breast cancer patients receiving (neo-) adjuvant chemotherapy with 5-fluorouracil, epirubicin and cyclophosphamide, and docetaxel

Vulsteke, C. and Pfeil, A. M. and Schwenkglenks, M. and Pettengell, R. and Szucs, T. D. and Lambrechts, D. and Peeters, M. and van Dam, P. and Dieudonné, A. S. and Hatse, S. and Neven, P. and Paridaens, R. and Wildiers, H.. (2014) Impact of genetic variability and treatment-related factors on outcome in early breast cancer patients receiving (neo-) adjuvant chemotherapy with 5-fluorouracil, epirubicin and cyclophosphamide, and docetaxel. Breast cancer research and treatment, Vol. 147, H. 3. pp. 557-570.

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Official URL: http://edoc.unibas.ch/dok/A6348531

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Abstract

To assess the impact of patient-related factors, including genetic variability in genes involved in the metabolism of chemotherapeutic agents, on breast cancer-specific survival (BCSS) and recurrence-free interval (RFI). We selected early breast cancer patients treated between 2000 and 2010 with 4-6 cycles of (neo-)adjuvant 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) or 3 cycles FEC followed by 3 cycles docetaxel. Tumor stage/subtype; febrile neutropenia and patient-related factors such as selected single nucleotide polymorphisms and baseline laboratory parameters were evaluated. Multivariable Cox regression was performed. Of 991 patients with a mean follow-up of 5.2 years, 152 (15.3 %) patients relapsed and 63 (6.4 %) patients died. Advanced stage and more aggressive subtype were associated with poorer BCSS and RFI in multivariable analysis (p > 0.0001). Associations with worse BCSS in multivariable analysis were: homozygous carriers of the rs1057910 variant C-allele in CYP2C9 (hazard ratio [HR] 30.4; 95 % confidence interval [CI] 6.1-151.5; p > 0.001) and higher white blood cell count (WBC) (HR 1.2; 95 % CI 1.0-1.3; p = 0.014). The GT genotype of the ABCB1 variant rs2032582 was associated with better BCSS (HR 0.5; 95 % CI 0.3-0.9, p = 0.021). Following associations with worse RFI were observed: higher WBC (HR 1.1; 95 % CI 1.0-1.2; p = 0.026), homozygous carriers of the rs1057910 variant C-allele in CYP2C9 (HR 10.9; 95 % CI 2.5-47.9; p = 0.002), CT genotype of the CYBA variant rs4673 (HR 1.8; 95 % CI 1.2-2.7; p = 0.006), and G-allele homozygosity for the UGT2B7 variant rs3924194 (HR 3.4; 95 % CI 1.2-9.7, p = 0.023). Patient-related factors including genetic variability and baseline white blood cell count, impacted on outcome in early breast cancer.
Faculties and Departments:03 Faculty of Medicine > Departement Public Health > Pharmazeutische Medizin ECPM > Pharmazeutische Medizin (Szucs)
UniBasel Contributors:Pfeil, Alena
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Springer
ISSN:0167-6806
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:10 Apr 2015 09:12
Deposited On:10 Apr 2015 09:12

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