Introduction. While standard doses of adjuvant fluoropyrimidine-based chemotherapies are generally safe for most patients, the risk of severe toxicity is increased for patients with dihydropyimidine dehydrogenase deficiency (DPYD).
Aims. We examined the cost-effectiveness of offering DPYD pharmacogenetic-guided care versus the current standard of care (SoC) for local or metastatic breast cancer patients in Qatar.
Methods. We developed a two-stage decision analysis, with an analytic tree model over a 6-month, followed by a life-table Markov model over a lifetime horizon. We compared the current SoC with the alternate strategy of DPYD genetic screening in Qatari patients eligible for adjuvant fluoropyrimidine therapy. Clinical outcomes and utilities were obtained from published studies, while healthcare costs were estimated from Hamad Medical Corporation, Qatar. The short-term outcome included the incremental cost-effectiveness ratio (ICER), defined as cost per survival without grade III/IV ADRs at six months. The long-term outcome was the ICER, defined as cost per quality-adjusted life year (QALY) gained, with a 3% annual discount rate. The study adopted a public hospital perspective. Sensitivity analyses were conducted to explore the impact of key input parameters on the robustness of the model.
Results. In the short-term model, at its base case, DPYD genomic screening was dominant over SoC with a mean cost-saving of QAR 84,585 (95% confidence interval (CI), 45,270–151,657). In the long-term model, compared to the current SoC, DPYD genetic screening would result in an ICER of QAR 21,107 (95% CI -59,382-145,664) per QALY gained.
Discussion. Based on our model, implementing DPYD genetic screening to detect DPYD mutations in breast cancer patients before therapy initiation is a cost-saving and cost-effective strategy in Qatar.

Introduction: Breast cancer (BC) survivors may have an increased risk of endometrial cancer due to endocrine therapy, but the risk is unknown among Japanese women, especially by type of endocrine treatment (tamoxifen, aromatase inhibitors).
Aims: We aimed to determine the risk of endometrial cancer overall and by type of endocrine treatment among BC survivors.
Methods: We conducted a matched cohort study using data from the JMDC claims database. Between January 2005 and December 2019, women aged 18–74 years with and without BC were matched with 1:4 ratio for age and entry timing to the database. We estimated and compared the risks for endometrial cancer between the groups, using the stratified Cox regression analysis further adjusting for BMI, smoking, diabetes, and oral contraceptives. In addition, we estimated the risk by endocrine treatment regimen (tamoxifen, aromatase inhibitor, tamoxifen, and no endocrine therapy) during the first year after the BC diagnosis, using the unstratified Cox regression analysis in which the reference group was women without BC, and patients were followed from one year after the matching, further adjusted for chemotherapy (anthracycline, taxane).
Results: Among 24,017 BC survivors and 96,068 matched women (mean age 50.5 years), endometrial cancer occurred among 56 and 38 women (incidence rate of 0.7 and 0.1 cases/1000 person-years, respectively), with the adjusted hazard ratio of 8.10 (95% CI 3.97–16.5). By treatment, the tamoxifen (n=10164, mean age 45.9 years), aromatase inhibitor (n=5468, 58.9 years), and no hormone therapy (n=7765, 50.4 years) groups had 26, 4, 10 endometrial cancer cases, and the adjusted hazard ratios were 6.86 (3.59–13.13), 1.45 (0.33–6.51), and 5.35 (2.37–12.09), respectively, compared to women without BC.
Discussion: Japanese BC survivors showed an increased risk of endometrial cancer than women without BC, and the risk varied by the type of endocrine therapy.

Introduction: Endocrine therapy plays a pivotal role in the management of hormone-receptor-positive early-stage breast cancer in postmenopausal women. Despite the increasing preference for aromatase inhibitors (AIs) over tamoxifen, their cardiovascular safety profile remains an ongoing concern.

Aims: This study compares the cardiovascular risks associated with AIs and tamoxifen in postmenopausal women with non-metastatic breast cancer.

Methods: A retrospective multinational cohort study was conducted using data from the US SEER-Medicare database and Taiwan’s national claims database and cancer registry. The study population comprised postmenopausal women diagnosed with stage I-III breast cancer from 2010-2019 in the US and from 2011-2020 in Taiwan. Patients were divided into two groups based on their initial therapy with AIs or tamoxifen after surgery. The study outcomes were 3-point major adverse cardiovascular events (MACE) and venous thromboembolism (VTE). Covariate balance was ensured through inverse probability of treatment weighting. Cardiovascular risks were evaluated separately for each country’s cohort using cause-specific hazard models.

Results: The cohorts included 36,931 US patients (89.6% AIs users) and 22,573 Taiwanese patients (71.1 % AIs users) for MACE analysis, and 31,706 US patients (89.4% AIs users) and 21,957 Taiwanese patients (71.0% AIs users) for VTE analysis. No significant increase in MACE risk was observed for AI users compared to tamoxifen users in either country (US hazard ratio [HR]: 1.13, 95% CI 0.83-1.52; Taiwan HR 1.21, 95% CI 0.85-1.70). Conversely, AI users in the US showed a lower risk of VTE (HR 0.35, 95% CI 0.27-0.45), while the pattern was not statistically significant in the Taiwanese cohort (HR 0.72, 95% CI 0.42-1.24).

Discussion: AIs do not elevate MACE risk compared with tamoxifen in postmenopausal breast cancer patients. The observed ethnic variations in VTE risks underscore potential differences in thrombotic responses to endocrine therapy, consistent with prior research indicating lower VTE risks in Asian populations.

Introduction: Abiraterone and enzalutamide are oral novel hormonal agents (NHAs) used in prostate cancer (PCa) management. By inhibiting androgen biosynthesis and receptor activity, NHAs can cause metabolic alterations, leading to adverse cardiometabolic events. However, data on their cardiovascular safety compared to traditional chemotherapy are scarce.

Aims: To evaluate the risk of major adverse cardiovascular events (MACE) of NHAs and chemotherapy for PCa patients in Hong Kong.

Methods: This cohort study used electronic health records in Hong Kong. Patients with PCa treated with NHAs (abiraterone and enzalutamide) between 2001 and 2019 were included in the exposed group, and those with docetaxel were active controls. Primary outcome was MACE over 10 years of follow-up. Propensity score matching (PSM) was used to control confounding factors. Cox regression was used to estimate the hazard ratios (HR) and competing risks were accounted for using the Fine-Gray method. Sensitivity analyses censored patients at drug switching and filled missing prostate specific antigen (PSA) levels using multiple imputations.

Results: Among 25,821 PCa patients, 2729 (10.57%) had used adjuvant treatments. After PSM, 617 NHA users and 317 controls were included. MACE incidence rate was 70.28 and 35.76 per 1000 person-years in NHA and docetaxel users, respectively. NHA use was associated with increased risk of MACE (HR 1.61, 95% confidence interval [CI] 1.10–2.35), supported by the Fine-Gray estimator (subdistribution HR 1.52, 95% CI 1.04-2.15) and remained consistent after multiple imputation for missing PSA values (HR 1.59, 95% CI 1.12–2.26). Censoring at drug switching showed elevated risk without statistical significance (HR 1.39, 95% CI 0.96–2.03).

Conclusions: NHA use is associated with elevated risk of MACE compared to docetaxel. Our findings emphasize the need for baseline cardiovascular risk assessment before choosing between NHA and docetaxel as adjunct treatment, and close monitoring of cardiovascular complications in patients receiving NHAs.

Introduction: Among men with prostate cancer, androgen deprivation therapy (ADT) therapy frequently causes adverse cardiometabolic events, but data on primary prevention using statins or metformin are scarce.

Aims: To investigate the effectiveness of statins and metformin against major adverse cardiovascular events (MACE) in high-risk ADT-treated prostate cancer patients in Hong Kong.

Methods: This cohort study used electronic health records in Hong Kong. Men with prostate cancer treated with ADT between 2004 and 2019, without a history but risk factors for atherosclerotic cardiovascular disease were included. New users of statins or metformin within one year after ADT initiation were compared with non-users using an index date one year after ADT initiation. Outcomes were MACE and all-cause mortality over 10 years of follow-up. Cox regression was used to estimate the hazard ratios (HR) and competing risks were accounted for using the Fine-Gray method to estimate subdistribution HR.

Results: Among 11,457 eligible men, 235 statin users and 129 metformin users with high cardiovascular risks were identified. After propensity score matching, incidence rates of MACE were 14.29 and 35.19 per 1000 person-years in statin and metformin new users, respectively. Neither statin (HR 0.82, 95% confidence interval [CI] 0.39 – 1.70) nor metformin initiation (HR 1.27, 95% CI 0.65 – 2.47) was associated with a reduced risk of MACE. Statin initiation was associated with reduced all-cause mortality (HR 0.53, 95% CI 0.40 – 0.68), but not metformin. Competing risk analysis showed that statin initiation was associated with a reduced risk of MACE (sHR 0.49, 95% CI 0.26 – 0.92).

Conclusions: Statin initiation was associated with reduced cardiovascular risks and improved overall survival among high-risk patients undergoing ADT for prostate cancer, but not metformin. Further investigations are needed to validate the benefits of statins against cardiotoxicities of hormonal treatment for prostate cancer.

Introduction:
Tadalafil, commonly prescribed for benign prostatic hyperplasia, can be beneficial for patients with type 2 diabetes (T2DM) for glycemic markers and complications. However, evidence is lacking regarding the association between long-term use of tadalafil and incidence of T2DM.
Aims:
Therefore, this study aimed to assess the impact of tadalafil on the incidence of T2DM.
Methods:
We emulated a target trials of tadalafil use (5mg per day orally) and risk of T2DM using population-based claim database from 2014 to 2023 in Japan. The study cohort comprised patients who received at least two new prescriptions of tadalafil or alpha blocker for benign prostatic hyperplasia and had no history of diabetes diagnoses, no prescription of glucose lowering drugs, and no history of hemoglobin A1c ≥ 6.5%. The primary outcome was the incidence of T2DM defined using diagnostic code, prescription records, and laboratory data. Pooled logistic regression was used to estimate the adjusted risk ratios and 5-year cumulative incidence differences between tadalafil and alpha blockers using as treated approach.
Results:
A total of 5,180 participants initiated tadalafil treatment and were compared with 20,049 alpha-blocker initiators. The median follow-up time for each arm was 27.2 months [interquartile range (IQR) 12.0–47.9] in tadalafil users and 31.3 months (IQR 13.7–57.2) in alpha blocker users. The incidence rate of T2DM in tadalafil and alpha-blocker users was 5.4 [95% confidence interval (CI) 4.0–7.2) and 8.8 (95%CI 7.8–9.8) per 1,000-person years, respectively. Initiation of tadalafil was associated with a reduced risk of T2DM (risk ratio 0.47, 95%CI 0.39–0.62, 5-year cumulative incidence difference −0.031, 95%CI −0.040 – −0.019).
Discussion/Conclusion:
The incidence of T2DM appears to be lower in men with benign prostatic hyperplasia exposed to tadalafil than in those receiving alpha-blockers. This, tadalafil be more beneficial than alpha-blockers in preventing the development of T2DM.