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
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
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遗传变异和治疗相关因素对接受 5-氟尿嘧啶、表柔比星、环磷酰胺和多西紫杉醇（新）辅助化疗的早期乳腺癌患者结局的影响
DOI：
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发表时间：
2014
影响因子：
3.8
通讯作者：
Hans Wildiers
中科院分区：
文献类型：
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作者：
C. Vulsteke;A. Pfeil;M. Schwenkglenks;R. Pettengell;T. Szucs;Diether Lambrechts;Marc Peeters;P. V. Dam;A. Dieudonne;S. Hatse;P. Neven;R. Paridaens;Hans Wildiers
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.
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影响因子：
2.2
作者：
Lee, In Kyu;VanSaun, Michael N.;Gorden, D. Lee
通讯作者：
Gorden, D. Lee
影响因子：
50.5
作者：
Sun, Z.;Chen, J.;Yang, P.
通讯作者：
Yang, P.
影响因子：
45.3
作者：
Ganz, Patricia A.;Kwan, Lorna;Belin, Thomas R.
通讯作者：
Belin, Thomas R.
影响因子：
10.3
作者：
Hassett, Michael J.;O'Malley, A. James;Earle, Craig C.
通讯作者：
Earle, Craig C.
影响因子：
45.3
作者：
Woodward, WA;Strom, EA;Buchholz, TA
通讯作者：
Buchholz, TA