title: Non-genetic risk factors and predicting efficacy for docetaxel--drug-induced liver injury among metastatic breast cancer patients.
abstract: OBJECTIVE
  Docetaxel has been chosen as one of the most popular anticancer drugs in the treatment of breast cancer for more than a decade. There is increasingly awareness for the occurrence of docetaxel and/or docetaxel-drug-induced liver injury (DILI), although the underlying mechanism of occurrence and its risk factors remain unclear.
  
  
  METHODS
  We conducted a retrospective cohort study to identify non-genetic risk factors for docetaxel-DILI among 647 metastasis breast cancer patients treated with docetaxel-containing regimens.
  
  
  RESULTS
  Sixty-seven (10.36%) patients were diagnosed as docetaxel-DILI. By logistic regression analysis, premenopausal status (odds ratio [OR][95% confidence interval {CI}] = 2.24 [1.30-3.87]), past hepatitis B virus (HBV) infections (OR [95% CI] = 4.23 [1.57-11.42]), liver metastasis (OR [95% CI] = 3.70 [2.16-6.34]). The predominant occurrence of DILI was seen in groups with docetaxel combination regimens. (OR [95% CI] = 2.66 [1.59-4.55]). The potential increasing occurrence of docetaxel-DILI was associated with multiple risk factors in an exposure-response manner (P < 0.001), and patients with more than three risk factors would be exposed to a 36.61-fold risk of DILI (95% CI = 10.18-131.62). Further analysis by the risk score and area under the receiver-operator characteristic curve (AUC) showed that those four factors contributed to an AUC of 0.7536 (95% CI = 0.70-0.81), with a predictive sensitivity of 74.63% and specificity of 65.17%.
  
  
  CONCLUSIONS
  Docetaxel-DILI with a relatively higher incidence should be addressed among metastatic breast cancer patients. Four predominant risk factors, including premenopausal status, past HBV infection, liver metastasis, and docetaxel combination regimens, were potential predicators for DILI.
authors.affiliation: Department of Medical Oncology, Beijing Cancer Hospital, Peking University School of Oncology, Beijing, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.forename: Xu
authors.initials: X
authors.lastname: Liang
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zheng
authors.forename: Yulin
authors.initials: Y
authors.lastname: Zhu
authors.forename: Ying
authors.initials: Y
authors.lastname: Yan
authors.forename: Ningning
authors.initials: N
authors.lastname: Dong
authors.forename: Lijun
authors.initials: L
authors.lastname: Di
authors.forename: Guohong
authors.initials: G
authors.lastname: Song
authors.forename: Xinna
authors.initials: X
authors.lastname: Zhou
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wang
authors.forename: Huabing
authors.initials: H
authors.lastname: Yang
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
authors.forename: Herbert Kim
authors.initials: HK
authors.lastname: Lyerly
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D016009:Chi-Square Distribution; D000077143:Docetaxel; D005260:Female; D006509:Hepatitis B / Q000150:complications; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D016015:Logistic Models; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D017697:Premenopause; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D043823:Taxoids; D000077143:Docetaxel