Tamoxifen metabolism predicts drug concentrations and outcome in premenopausal patients with early breast cancer

Tamoxifen is the standard-of-care treatment for estrogen receptor-positive premenopausal breast cancer. We examined tamoxifen metabolism via blood metabolite concentrations and germline variations of CYP3A5, CYP2C9, CYP2C19 and CYP2D6 in 587 premenopausal patients (Asians, Middle Eastern Arabs, Caucasian-UK; median age 39 years) and clinical outcome in 306 patients. N-desmethyltamoxifen (DM-Tam)/(Z)-endoxifen and CYP2D6 phenotype significantly correlated across ethnicities (R2: 53%, P<10?77). CYP2C19 and CYP2C9 correlated with norendoxifen and (Z)-4-hydroxytamoxifen concentrations, respectively (P<0.001). DM-Tam was influenced by body mass index (P<0.001). Improved distant relapse-free survival (DRFS) was associated with decreasing DM-Tam/(Z)-endoxifen (P=0.036) and increasing CYP2D6 activity score (hazard ratio (HR)=0.62; 95% confidence interval (CI), 0.43–0.91; P=0.013). Low (<14?nM) compared with high (>35?nM) endoxifen concentrations were associated with shorter DRFS (univariate P=0.03; multivariate HR=1.94; 95% CI, 1.04–4.14; P=0.064). Our data indicate that endoxifen formation in premenopausal women depends on CYP2D6 irrespective of ethnicity. Low endoxifen concentration/formation and decreased CYP2D6 activity predict shorter DRFS

Factors associated with prolonged length of stay for elective hepatobiliary and neurosurgery patients: a retrospective medical record review

Abstract Background Patients with prolonged length of hospital stay (LOS) not only increase their risks of nosocomial infections but also deny other patients access to inpatient care. Hepatobiliary (HPB) malignancies have some of highest incidences in East and Southeast Asia and the management of patients undergoing HPB surgeries have yet to be standardized. With improved neurosurgery techniques for intracranial aneurysms and tumors, neurosurgeries (NS) can be expected to increase. Elective surgeries account for far more operations than emergencies surgeries. Thus, with potentially increased numbers of elective HPB and NS, this study seeks to explore perioperative factors associated with prolonged LOS for these patients to improve safety and quality of practice. Methods A retrospective cross-sectional medical record review study from January 2014 to January 2015 was conducted at a 1250-bed tertiary academic hospital in Singapore. All elective HPB and NS patients over 18 years old were included in the study except day and emergency surgeries, resulting in 150 and 166 patients respectively. Prolonged LOS was defined as above median LOS based on the complexity of the surgical procedure. The predictor variables were preoperative, intraoperative, and postoperative factors. Student’s t-test and stepwise logistic regression analyses were conducted to determine which factors were associated with prolonged LOS. Results Factors associated with prolonged LOS for the HPB sample were age and admission after 5 pm but for the NS sample, they were functional status, referral to occupational therapy, and the number of hospital-acquired infections. Conclusion Our findings indicate that preoperative factors had the greatest association with prolonged LOS for HPB and NS elective surgeries even after adjusting for surgical complexity, suggesting that patient safety and quality of care may be improved with better pre-surgery patient preparation and admission practices