Sandar Tin Tin

This population‐based cohort study investigated whether the subsequent risk of breast cancer after ductal carcinoma in situ (DCIS) has changed over time in New Zealand women diagnosed between 2000 and 2022, using data from the New Zealand Breast Cancer Foundation National Register. The primary outcome was ipsilateral breast event, including invasive cancer (iIBC) or DCIS (iDCIS). Fine‐Gray subdistributional hazard models assessed associations with demographic and clinical factors, and a 5‐year landmark analysis evaluated subsequent risk among women who remained event‐free at 5 years. Among 5830 patients (median follow‐up 4.8 years), the overall 5‐year cumulative risk of iIBC was 3.3% (95% CI: 2.7%, 3.9%). In the 5‐year landmark cohort, the subsequent 5‐year risk was 4.1% (3.3%, 5.0%). Corresponding iDCIS rates were 2.5% (2.0%, 3.0%) and 1.7% (1.2%, 2.3%), respectively. Age < 45 years at diagnosis and DCIS size > 20 mm were associated with a higher iIBC risk, but the association with younger age attenuated in the landmark analysis. Compared with breast conserving surgery (BCS) alone, both radiotherapy following BCS and mastectomy were associated with a lower iIBC risk; however, the association for radiotherapy was not evident at the 5‐year landmark. Overall, women with DCIS had a 5.25‐fold higher risk of invasive breast cancer than the general population (95% CI: 4.79, 5.73). Our findings support the importance of long‐term mammographic surveillance, particularly for women with larger DCIS, those treated with BCS, and possibly younger women.

Background: Adiposity, measured by body mass index (BMI), is a known risk factor for postmenopausal breast cancer. However, whether the association of BMI with breast cancer risk differs among women with and without cardiovascular diseases (CVDs) or type 2 diabetes (T2D) is uncertain.Methods: This study used individual participant data from the European Prospective Investigation into Cancer and Nutrition (EPIC) and UK Biobank (UKB) that included 168,547 postmenopausal women who were free of cancer, T2D, and CVD at recruitment. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with multivariable‐adjusted Cox regression for associations between BMI and incident breast cancer by T2D and CVD status. Incidence rates per 1000 person‐years and rate differences between observed and expected joint associations of adiposity and CVD or T2D for breast cancer were estimated. Study‐specific estimates were meta‐analyzed.Results: After a median follow‐up of 10.7 years in EPIC and 10.9 years in UKB, 6793 postmenopausal women developed breast cancer. In the meta‐analysis of both cohorts, BMI (per 1‐SD increment, 5 kg/m²) was more strongly associated with breast cancer risk in women with CVD (HR, 1.31; 95% CI, 1.16 to 1.47) than in women without CVD (HR, 1.13; 95% CI, 1.11 to 1.16) (p_interaction = .02). T2D did not modify breast cancer risk (p_interaction = .33). The meta‐analyzed joint association of overweight or obesity (BMI, ≥25 kg/m²) and CVD led to 1.53 (95% CI, 0.35 to 2.71) more cases of breast cancer per 1000 person‐years than expected but no such joint association was observed with T2D.Conclusions: Adiposity‐associated risk of breast cancer was substantially higher among women with CVD as compared to those without CVD.

Background: The association between statins and breast cancer-specific mortality and recurrence has been examined in several previous observational studies and meta-analyses. However, potentially important effect modifiers have not often been explored in previous meta-analyses. In this study, an updated systematic review and meta-analysis was undertaken to ascertain the association between statins and both breast cancer death (BCD) and breast cancer recurrence (BCR). Methods: Articles were sourced from various databases up until the 13th of June 2024, and effect estimates were pooled using the random effects model. Subgroup analyses were conducted by the potential for immortal time bias (ITB), type of statin (lipophilic vs hydrophilic), estrogen receptor status (positive vs negative), stage (‘early’ vs ‘advanced’), and type of postdiagnostic use (‘new’ vs ‘prevalent’ user). Results: Pooled results showed that there was a statistically significant protective association between statin use and both BCD (21 studies, hazard ratio = 0.81, 95% CI: 0.75–0.87) and BCR (20 studies, HR = 0.81, 95% CI: 0.74–0.89). Lipophilic statins were more protective than hydrophilic statins with BCD as the outcome, and there were suggestions of a more protective association in studies with ITB and in ER+ patients with BCR as the outcome. There was little evidence of effect modification by stage or type of postdiagnostic use. Conclusion: In this meta-analysis, we observed that statin use, particularly lipophilic statin use, was associated with favourable outcomes for BCD and BCR.

Background: The choice of transport mode may influence cancer risk by affecting physical activity level, sedentary behaviour, and exposure to environmental pollution. This study investigated the associations between commuting modes and 16 site-specific cancers in the UK Biobank. Methods: The UK Biobank is a prospective cohort study involving about 500 000 participants. Information on transport modes was collected at recruitment, and incident cancer cases were identified through linkage to national cancer registries. Multivariable Cox proportional hazards models were used. Results: There were 252 334 employed participants included, and 15 828 incident cancer cases were identified over a median follow-up of 11.7 years. Compared to the car-only mode, cycling (exclusively or combined with any other modes) was associated with a lower risk of colon [hazard ratio (HR): 0.72; 95% confidence interval: 0.53–0.96], renal (HR: 0.60; 0.38–0.96), and stomach (HR: 0.27; 0.10–0.71) cancers. Walking (exclusively or combined with any motorized mode) was associated with a lower risk of renal (HR: 0.67; 0.49–0.92) and liver (HR: 0.55; 0.31–0.98) cancers. Public transport users were less engaged in other physical activities, and its use was associated with a higher risk of bladder cancer (HR: 1.39; 1.01–1.90). Conclusions: Active commuting, even combined with motorized modes, is associated with a lower risk of some common cancers.

Background: Health care system–wide outcomes from routine treatment with erlotinib and gefitinib are incompletely understood. Objective: The aim of the study is to describe the effectiveness of erlotinib and gefitinib during the first decade of their routine use for treating advanced epidermal growth factor receptor (EGFR) mutation-positive nonsquamous non–small cell lung cancer in the entire cohort of patients treated in Aotearoa New Zealand. Methods: Patients were identified, and data collated from national pharmaceutical dispensing, cancer registration, and mortality registration electronic databases by deterministic data linkage using National Health Index numbers. Time-to-treatment discontinuation and overall survival were measured from the date of first dispensing of erlotinib or gefitinib and analyzed by Kaplan-Meier curves. Associations of treatment outcomes with baseline factors were evaluated using univariable and multivariable Cox regressions. Results: Overall, 752 patients were included who started treatment with erlotinib (n=418) or gefitinib (n=334) before October 2020. Median time-to-treatment discontinuation was 11.6 (95% CI 10.8‐12.4) months, and median overall survival was 20.1 (95% CI 18.1‐21.6) months. Shorter time-to-treatment discontinuation was independently associated with high socioeconomic deprivation (hazard ratio [HR] 1.3, 95% CI 1.1‐1.5 compared to the New Zealand Index of Deprivation 1‐4 group), EGFR L858R mutations (HR 1.3, 95% CI 1.1‐1.6 compared to exon 19 deletion), and distant disease at cancer diagnosis (HR 1.4, 95% CI 1.2‐1.7 compared to localized or regional disease). The same factors were independently associated with shorter overall survival. Outcome estimates and predictors remained unchanged in sensitivity analyses. Conclusions: Outcomes from routine treatment with erlotinib and gefitinib in New Zealand patients with advanced EGFR-mutant nonsquamous non–small cell lung cancer are comparable with those reported in randomized trials and other health care system–wide retrospective cohort studies. Socioeconomic status, EGFR mutation subtype, and disease extent at cancer diagnosis were independent predictors of treatment outcomes in that setting.

Purpose: The current standard of treatment for ductal carcinoma in situ (DCIS) is surgery with or without adjuvant radiotherapy. With a growing debate about overdiagnosis and overtreatment of low-risk DCIS, active surveillance is being explored in several ongoing trials. We conducted a systematic review and meta-analysis to evaluate the recurrence of low-risk DCIS under various treatment approaches. Methods: PubMed, Embase, Web of Science, and Cochrane were searched for studies reporting ipsilateral breast tumour event (IBTE), contralateral breast cancer (CBC), and breast cancer-specific survival (BCSS) rates at 5 and 10 years in low-risk DCIS. The primary outcome was invasive IBTE (iIBTE) defined as invasive progression in the ipsilateral breast. Results: Thirty three eligible studies were identified, involving 47,696 women with low-risk DCIS. The pooled 5-year and 10-year iIBTE rates were 3.3% (95% confidence interval [CI]: 1.3, 8.1) and 5.9% (95% CI: 3.8, 9.0), respectively. The iIBTE rates were significantly lower in patients who underwent surgery compared to those who did not, at 5 years (3.5% vs. 9.0%, P = 0.003) and 10 years (6.4% vs. 22.7%, P = 0.008). Similarly, the 10-year BCSS rate was higher in the surgery group (96.0% vs. 99.6%, P = 0.010). In patients treated with breast-conserving surgery, additional radiotherapy significantly reduced IBTE risk, but not total-CBC risk. Conclusion: This review showed a lower risk of progression and better survival in women who received surgery and additional RT for low-risk DCIS. However, our findings were primarily based on observational studies, and should be confirmed with the results from the ongoing trials.

Background: Starting in 2010, the epidermal growth factor receptor (EGFR) kinase inhibitors erlotinib and gefitinib were introduced into routine use in Aotearoa New Zealand (NZ) for treating advanced lung cancer, but their impact in this setting is unknown. Objective: The study described in this protocol aims to understand the effectiveness and safety of these new personalized lung cancer treatments and the contributions made by concomitant medicines and other factors to adverse outcomes in the general NZ patient population. A substudy aimed to validate national electronic health databases as the data source and the methods for determining patient eligibility and identifying outcomes and variables. Methods: This study will include all NZ patients with advanced EGFR mutation–positive lung cancer who were first dispensed erlotinib or gefitinib before October 1, 2020, and followed until death or for at least 1 year. Routinely collected health administrative and clinical data will be collated from national electronic cancer registration, hospital discharge, mortality registration, and pharmaceutical dispensing databases by deterministic data linkage using National Health Index numbers. The primary effectiveness and safety outcomes will be time to treatment discontinuation and serious adverse events, respectively. The primary variable will be high-risk concomitant medicines use with erlotinib or gefitinib. For the validation substudy (n=100), data from clinical records were compared to those from national electronic health databases and analyzed by agreement analysis for categorical data and by paired 2-tailed t tests for numerical data. Results: In the validation substudy, national electronic health databases and clinical records agreed in determining patient eligibility and for identifying serious adverse events, high-risk concomitant medicines use, and other categorical data with overall agreement and κ statistic of >90% and >0.8000, respectively; for example, for the determination of patient eligibility, the comparison of proxy and standard eligibility criteria applied to national electronic health databases and clinical records, respectively, showed overall agreement and κ statistic of 96% and 0.8936, respectively. Dates for estimating time to treatment discontinuation and other numerical variables and outcomes showed small differences, mostly with nonsignificant P values and 95% CIs overlapping with zero difference; for example, for the dates of the first dispensing of erlotinib or gefitinib, national electronic health databases and clinical records differed on average by approximately 4 days with a nonsignificant P value of .33 and 95% CIs overlapping with zero difference. As of May 2024, the main study is ongoing. Conclusions: A protocol is presented for a national whole-of-patient-population retrospective cohort study designed to describe the safety and effectiveness of erlotinib and gefitinib during their first decade of routine use in NZ for treating EGFR mutation–positive lung cancer. The validation substudy demonstrated the feasibility and validity of using national electronic health databases and the methods for determining patient eligibility and identifying the study outcomes and variables proposed in the study protocol. Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12615000998549; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368928 International Registered Report Identifier (IRRID): DERR1-10.2196/51381

Background: The mechanisms underlying alcohol‐induced breast carcinogenesis are not fully understood but may involve hormonal changes.Methods: Cross‐sectional associations were investigated between self‐reported alcohol intake and serum or plasma concentrations of estradiol, estrone, progesterone (in premenopausal women only), testosterone, androstenedione, dehydroepiandrosterone sulfate, and sex hormone binding globulin (SHBG) in 45 431 premenopausal and 173 476 postmenopausal women. Multivariable linear regression was performed separately for UK Biobank, European Prospective Investigation into Cancer and Nutrition, and Endogenous Hormones and Breast Cancer Collaborative Group, and meta‐analyzed the results. For testosterone and SHBG, we also conducted Mendelian randomization and colocalization using the ADH1B (alcohol dehydrogenase 1B) variant (rs1229984).Results: Alcohol intake was positively, though weakly, associated with all hormones (except progesterone in premenopausal women), with increments in concentrations per 10 g/day increment in alcohol intake ranging from 1.7% for luteal estradiol to 6.6% for postmenopausal dehydroepiandrosterone sulfate. There was an inverse association of alcohol with SHBG in postmenopausal women but a small positive association in premenopausal women. Two‐sample randomization identified positive associations of alcohol intake with total testosterone (difference per 10 g/day increment: 4.1%; 95% CI, 0.6–7.6) and free testosterone (7.8%; 4.1–11.5), and an inverse association with SHBG (–8.1%; –11.3% to –4.9%). Colocalization suggested a shared causal locus at ADH1B between alcohol intake and higher free testosterone and lower SHBG (posterior probability for H4, 0.81 and 0.97, respectively).Conclusions: Alcohol intake was associated with small increases in sex hormone concentrations, including bioavailable fractions, which may contribute to its effect on breast cancer risk.