scholarly journals Tamoxifen Pharmacogenetics and Metabolism: Results From the Prospective CYPTAM Study

2019 ◽  
Vol 37 (8) ◽  
pp. 636-646 ◽  
Author(s):  
Anabel Sanchez-Spitman ◽  
Vincent Dezentjé ◽  
Jesse Swen ◽  
Dirk Jan A.R. Moes ◽  
Stefan Böhringer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Outcome ◽  
Cox Regression ◽  
Early Stage ◽  
Hazard Ratio ◽  
Adjusted Hazard Ratio ◽  
Early Stage Breast Cancer ◽  
Adjuvant Tamoxifen ◽  
Cyp2d6 Genotype ◽  
Cox Regression Analysis

PURPOSE Tamoxifen is widely prescribed as adjuvant therapy in patients with early-stage breast cancer. It has been postulated that concentrations of endoxifen, the active metabolite of tamoxifen, are a better predictor of tamoxifen efficacy than CYP2D6 genotypes. Although in a retrospective study, an endoxifen threshold of 5.9 ng/mL for efficacy was described, confirmation based on prospective studies is lacking. The objective of the prospective CYPTAM (The Netherlands National Trial Register: NTR1509) study was to associate endoxifen concentrations and CYP2D6 genotypes with clinical outcome in patients with early-stage breast cancer receiving tamoxifen. PATIENTS AND METHODS From February 2008 to December 2010, patients with breast cancer treated with adjuvant tamoxifen were included. Patients could be enrolled up to a maximum of 12 months after tamoxifen initiation. Blood samples were retrieved for CYP2D6 genotyping and endoxifen measurements by Amplichip (Roche Diagnostics, Indianapolis, IN) and high-performance liquid chromatography–tandem mass spectrometry, respectively. Endoxifen concentrations were analyzed as a continuous variable, classifying patients into quartiles and using an endoxifen threshold of 5.9 ng/mL. Endoxifen concentrations and CYP2D6 genotypes were associated with relapse-free survival (censored at the time of tamoxifen discontinuation; RFSt) by Cox regression analysis. RESULTS A total of 667 pre- and postmenopausal patients were enrolled and had received tamoxifen for a median time of 0.37 years (range, 0.23 to 0.6 years) before study entry. No association was found between endoxifen concentrations and RFSt (adjusted hazard ratio, 0.991; 95% CI, 0.946 to 1.038; P = .691). Also, neither categorizing endoxifen concentrations into quartiles nor using 5.9 ng/mL as threshold altered these results. In addition, no association was found between CYP2D6 genotype and RFSt (adjusted hazard ratio, 0.929; 95% CI, 0.525 to 1.642; P = .799). CONCLUSION This prospective clinical study shows no association between endoxifen concentrations or CYP2D6 genotypes and clinical outcome in patients with early-stage breast cancer receiving adjuvant tamoxifen.

scholarly journals Do Children With Constipation Have Increased Risk of Asthma? Real-World Data From a Nationwide Population-Based Cohort Study

2021 ◽  
Vol 9 ◽  
Author(s):  
Yen-Chu Huang ◽  
Meng-Che Wu ◽  
Yu-Hsun Wang ◽  
James Cheng-Chung Wei
Keyword(s):  
Cohort Study ◽  
Cox Regression ◽  
Population Based ◽  
Hazard Ratio ◽  
Adjusted Hazard Ratio ◽  
Research Database ◽  
Real World Data ◽  
Childhood Disorders ◽  
Cox Regression Analysis ◽  
Increased Risk

Background: Asthma is one of the most burdensome childhood disorders. Growing evidence disclose intestinal dysbiosis may contribute to asthma via the gut-lung axis. Constipation can lead to alteration of the gut microbiota. The clinical impact of constipation on asthma has not been researched. Therefore, we aim to assess whether pediatric constipation influence the risk of developing asthma by a nationwide population-based cohort study.Methods: We analyzed 10,363 constipated patients and 10,363 individuals without constipation between 1999 and 2013 from Taiwan's National Health Insurance Research Database. Analysis of propensity score was utilized to match age, sex, comorbidities, and medications at a ratio of 1:1. In addition, multiple Cox regression analysis was performed to evaluate the adjusted hazard ratio of asthma. Furthermore, sensitivity tests and a stratified analysis were performed.Results: After adjustment for age, sex, comorbidities, and medications, constipated patients had a 2.36-fold greater risk of asthma compared to those without constipation [adjusted hazard ratio (aHR): 2.36, 95% C.I. 2.04–2.73, p < 0.001]. Furthermore, the severity of constipation is associated with an increased risk of asthma; the adjusted hazard ratio was 2.25, 2.85, and 3.44 within < 3, 3–12, and ≥12 times of laxatives prescription within 1 year, respectively (p < 0.001).Conclusion: Constipation was correlated with a significantly increased risk of asthma. Pediatricians should be aware of the possibility of asthma in constipated patients. Further research is warranted to investigate the possible pathological mechanisms of this association.

Male breast cancer (MBC) in the VA population: A gender issue?

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 587-587 ◽  
Author(s):  
Z. Nahleh ◽  
R. Srikantiah ◽  
R. Komrokji ◽  
M. Safa ◽  
J. Pancoast ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cox Regression ◽  
Ductal Carcinoma ◽  
Early Stage ◽  
Statistical Significance ◽  
Clinical Stage ◽  
Hormonal Treatment ◽  
Cancer Site ◽  
Early Stage Disease ◽  
Cox Regression Analysis

587 Background: The incidence of MBC continues to rise. Few studies have addressed the differences between MBC and female breast cancer (FBC). Treatment for MBC has ben extrapolated from FBC regimens. The VA cancer registry (VACCR) provides a unique source to study MBC. This retrospective analysis aims at comparing the characteristics and outcome of MBC and FBC in the VA population. Methods: We reviewed the VACCR database between 1995 and 2005, for 120 VA medical centers. Primary breast cancer site codes were identified (500–508). Data was entered and analyzed using bio-statistical software SPSS. Results: A total of 3025 patients :612 MBC and 2413 FBC were compared. Mean age at diagnosis was 67 for MBC and 57 for FBC (p <0.005). More MBC patients were black. MBC patients presented with a significantly higher stage of disease, more node positive(N+) and larger tumor size. In MBC, ductal histology was more common while lobular and ductal carcinoma in situ were less common than in FBC. ER + and PR + tumors were significantly more common in MBC (60% vs 52% and 53% vs 47%, P< 0.005). MBC patients received less chemotherapy while no statistical difference in hormonal treatment was observed. The median overall survival (OS) was lower for MBC (7 years vs 9.8 years, p<0.005). OS was not significantly different for stage III and IV while OS was inferior for MBC in stage I (7 yr vs not reached, p 0.005) and stage II (6 vs 8.6yr, p 0.001). In N- tumors, OS was inferior in MBC (6.1 vs 14.6 yr, p<0.005) but not statistically different for N+ tumors . In ER + and PR + tumors, OS was inferior in MBC (7yr vs 8yr and 7.3 yr vs 9.8 yr p<0.005); however, no statistical significance was observed in ER - or PR - tumors. Using Cox regression analysis age, sex, clinical stage, nodal status were statistically independent prognostic factors while race, histology and grade were not. Conclusion: This study suggests differences in the biology, pathology, presentation, and survival between male and female VA breast cancer patients. Survival of MBC patients appears inferior in early stage disease and N- tumors suggesting gender differences in the tumor pathogenesis and biology. In hormone receptor + MBC, survival was also inferior despite similar hormonal treatment practices. This observational study calls for different approach and treatment strategies in MBC. No significant financial relationships to disclose.

Late Extended Adjuvant Treatment With Letrozole Improves Outcome in Women With Early-Stage Breast Cancer Who Complete 5 Years of Tamoxifen

2008 ◽  
Vol 26 (12) ◽  
pp. 1948-1955 ◽  
Author(s):  
Paul E. Goss ◽  
James N. Ingle ◽  
Joseph L. Pater ◽  
Silvana Martino ◽  
Nicholas J. Robert ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Performance Status ◽  
Cohort Analysis ◽  
Disease Free Survival ◽  
Early Stage Breast Cancer ◽  
Adjuvant Tamoxifen ◽  
Cox Models ◽  
Hormone Receptor Positive ◽  
Clinical Fractures

Purpose The National Cancer Institute of Canada Clinical Trials Group MA.17 trial examined the efficacy of letrozole (LET) started within 3 months of 5 years of adjuvant tamoxifen in postmenopausal hormone receptor–positive early-stage breast cancer. When the trial was unblinded, patients who received placebo (PLAC) were offered LET. Patients and Methods This cohort analysis describes the outcomes of women assigned PLAC at the initial random assignment after unblinding. Efficacy outcomes of women who chose LET (PLAC-LET group) were compared with those who did not (PLAC-PLAC group) by the hazard ratios and by P values calculated from Cox models that adjusted for imbalances between the groups. Toxicity analyses included only events that occurred after unblinding. Results There were 1,579 women in the PLAC-LET group (median time from tamoxifen, 2.8 years) and 804 in the PLAC-PLAC group. Patients in the PLAC-LET group were younger; had a better performance status; and were more likely to have had node-positive disease, axillary dissection, and adjuvant chemotherapy than those in the PLAC-PLAC group. At a median follow-up of 5.3 years, disease-free survival (DFS; adjusted hazard ratio [HR], 0.37; 95% CI, 0.23 to 0.61; P < .0001) and distant DFS (HR, 0.39; 95% CI, 0.20 to 0.74; P = .004) were superior in the PLAC-LET group. More self-reported new diagnoses of osteoporosis and significantly more clinical fractures occurred in the women who took LET (5.2% v 3.1%, P = .02). Conclusion Interpretation of this cohort analysis suggests that LET improves DFS and distant DFS even when there has been a substantial period of time since the discontinuation of prior adjuvant tamoxifen.

Sign in / Sign up

Export Citation Format

Share Document