title: The prognostic values of CYP2B6 genetic polymorphisms and metastatic sites for advanced breast cancer patients treated with docetaxel and thiotepa.
abstract: This study investigated interactive effects of CYP2B6 genotypes and liver metastasis on the prognosis of metastatic breast cancer patients who received combined chemotherapy of docetaxel and thiotepa. Totally 153 patients were retrospectively genotyped rs8192719 (c.1294 + 53C > T) and rs2279343 (c.785A > G). Kaplan-Meier method and Cox Proportional Hazard Regression model were used to estimate the survival. Patients with liver metastasis had worsen prognosis, conferring a 2.26-fold high risk of progression and 1.93-fold high risk of death (p < 0.05). Both CT/TT genotype of rs8192719 (c.1294 +  3C > T) and AG genotype of rs2279343 (c.785A > G) prolonged survival (p < 0.05). Furthermore, among liver metastatic patients, AG genotype of rs2279343 (c.785A > G) was associated with a 47% reduced risk of death and a 6-month-longer overall survival (p < 0.05). Among non-liver metastatic patients, hazard ratios of CT/TT genotype of rs8192719 (c.1294 + 53C > T) were 0.45 for progression and 0.40 for death; and the corresponding survival was improved by 6 months and 16 months, respectively (p < 0.05). Genotypes of CYP2B6 had an interaction with clinical efficacy of docetaxel and thiotepa on metastatic breast cancer patients; and metastatic sites also affected clinical responses. Further therapies should take into account of chemotherapy regimen, genotypes of metabolizing enzymes and metastatic sites for the particular subpopulation.
authors.affiliation: Beijing Key Laboratory of Therapeutic Cancer Vaccines, Beijing Shijitan Hospital, Capital Medical University Cancer Center, 10 Tieyi Road, Beijing 100038, China.
authors.forename: Qingkun
authors.initials: Q
authors.lastname: Song
authors.affiliation: Beijing Key Laboratory of Therapeutic Cancer Vaccines, Beijing Shijitan Hospital, Capital Medical University Cancer Center, 10 Tieyi Road, Beijing 100038, China.
authors.forename: Xinna
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Medical Oncology, Peking University Cancer Hospital &Institute. 52 Fucheng Rd, Beijing 100142, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Yongan Road 95, Beijing 100050, China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Dong
authors.affiliation: Beijing Key Laboratory of Therapeutic Cancer Vaccines, Beijing Shijitan Hospital, Capital Medical University Cancer Center, 10 Tieyi Road, Beijing 100038, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wang
authors.affiliation: Beijing Key Laboratory of Therapeutic Cancer Vaccines, Beijing Shijitan Hospital, Capital Medical University Cancer Center, 10 Tieyi Road, Beijing 100038, China.
authors.forename: Huabing
authors.initials: H
authors.lastname: Yang
authors.affiliation: Beijing Key Laboratory of Therapeutic Cancer Vaccines, Beijing Shijitan Hospital, Capital Medical University Cancer Center, 10 Tieyi Road, Beijing 100038, China.|Department of Surgery, Duke University Medical Center, 203 Research Drive, Suite 433, Box 2606, Durham, NC 27710, United States.
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Surgery, Duke University Medical Center, 203 Research Drive, Suite 433, Box 2606, Durham, NC 27710, United States.
authors.forename: H Kim
authors.initials: HK
authors.lastname: Lyerly
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D065702:Cytochrome P-450 CYP2B6 / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D018572:Disease-Free Survival; D000077143:Docetaxel; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011446:Prospective Studies; D043823:Taxoids / Q000627:therapeutic use*; D013852:Thiotepa / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D013852:Thiotepa; D065702:Cytochrome P-450 CYP2B6