Social characteristics and social benefit use among premenopausal breast cancer survivors in Denmark: a population-based cohort study.

PURPOSE: In 2020, one million women aged < 55 years were diagnosed with breast cancer globally. The impact of breast cancer and its treatments on these women's ability to work and need for social benefits may differ by social characteristics. We evaluated social benefit use following breast cancer by education and cohabitation. METHODS: We conducted a nationwide population-based cohort study, including women aged 18-55 years diagnosed with stage I-III breast cancer in Denmark during 2002-2011. Statistics Denmark provided information on cohabitation, education, and social benefit use from 1 year pre-diagnosis to 10 years post-diagnosis. We calculated weekly proportions of self-support, unemployment, disability pension, flexi jobs, and sick leave according to education and cohabitation. RESULTS: Of 5345 women, 81.8% were self-supporting, 4.5% received disability pensions, 1.6% had flexi jobs, 3.6% were on sick leave, and 5.5% were unemployed 1 year pre-diagnosis. Ten years post-diagnosis, the proportions were 69.0%, 13.0%, 10.5%, 3.4%, and 2.0% of 3663 survivors. Disability pensions and flexi jobs increased from 12.1 to 26.4% and 2.8 to 13.5% in women with short education, from 4.1 to 12.8% and 1.8 to 12.2% in women with medium education, and from 0.8 to 6.0% and 0.9 to 6.9% in longer educated. Disability pensions increased more in women living alone (7.8 to 19.9%), than in cohabiting women (3.6 to 11.3%). CONCLUSIONS: Use of social benefits reflecting lost ability to work was highest in less educated women and in women living alone. IMPLICATIONS FOR CANCER SURVIVORS: Awareness of these groups is crucial when tailoring efforts to support work participation in cancer survivors.

Clinical factors associated with patterns of endocrine therapy adherence in premenopausal breast cancer patients.

INTRODUCTION: Patients with hormone receptor positive breast cancer are recommended at least five years of adjuvant endocrine therapy, but adherence to this treatment is often suboptimal. We investigated longitudinal trends in adjuvant endocrine therapy (AET) adherence among premenopausal breast cancer patients and identified clinical characteristics, including baseline comorbidities and non-cancer chronic medication use, associated with AET adherence. METHODS: We included stage I-III premenopausal breast cancer patients diagnosed during 2002-2011 and registered in the Danish Breast Cancer Group clinical database who initiated AET. We used group-based trajectory modeling to describe AET adherence patterns. We also linked patients to Danish population-based registries and fit multinomial logistic models to compute odds ratios (ORs) and 95% confidence intervals (95% CIs) associating clinical characteristics with AET adherence patterns. RESULTS: We identified three adherence patterns among 4,353 women-high adherers (57%), slow decliners (36%), and rapid decliners (6.9%). Women with stage I disease (vs. stage II; OR: 1.9, 95% CI 1.5, 2.5), without chemotherapy (vs. chemotherapy; OR: 4.3, 95% CI 3.0, 6.1), with prevalent comorbid disease (Charlson Comorbidity Index score ≥ 1 vs. 0; OR: 1.6, 95% CI 1.1, 2.3), and with a history of chronic non-cancer medication use (vs. none; OR: 1.3, 95% CI 1.0, 1.8) were more likely to be rapid decliners compared with high adherers. CONCLUSIONS: Women with stage I cancer, no chemotherapy, higher comorbidity burden, and history of chronic non-cancer medication use were less likely to adhere to AET. Taking steps to promote adherence in these groups of women may reduce their risk of recurrence.

Impact of type 2 diabetes on complications after primary breast cancer surgery: Danish population-based cohort study.

BACKGROUND: Knowledge is sparse on the impact of type 2 diabetes (T2D) on surgical outcomes after breast cancer surgery. This study investigated the association between T2D and risk of complications after primary breast cancer surgery, and evaluated the biological interaction between T2D and co-morbidities. METHODS: Using the Danish Breast Cancer Group clinical database, a cohort of all Danish women diagnosed with early-stage breast cancer during 1996-2022 was created. All patients underwent mastectomy or breast-conserving surgery. Information on prevalent T2D was collected from Danish medical and prescription registries. Surgical complications were defined as hospital diagnoses for medical or surgical complications developing within 30 days after primary breast cancer surgery. The 30-day cumulative incidence proportion of complications was calculated, and Cox regression was used to estimate HRs. Interaction contrasts were computed to determine the additive interaction between T2D and co-morbidities on the incidence rate of complications. RESULTS: Among 98 589 women with breast cancer, 6332 (6.4%) had T2D at breast cancer surgery. Overall, 1038 (16.4%) and 9861 (10.7%) women with and without T2D developed surgical complications, yielding cumulative incidence proportions of 16 (95% c.i. 15 to 17) and 11 (10 to 11)% respectively, and a HR of 1.43 (95% c.i. 1.34 to 1.53). The incidence rate of surgical complications explained by the interaction of T2D with moderate and severe co-morbidity was 21 and 42%, respectively. CONCLUSION: Women with breast cancer and T2D had a higher risk of complications after primary breast cancer surgery than those without T2D. A synergistic effect of T2D and co-morbidity on surgical complications can explain this association.

Extracting Systemic Anticancer Treatment Lines from the Danish National Patient Registry for Solid Tumour Patients Treated in the North Denmark Region Between 2009 and 2019.

Background: Reconstructing patient treatment trajectories is important to generate real-world evidence for epidemiological studies. The Danish National Patient Registry (DNPR) contains information about drug prescriptions and could therefore be used to reconstruct treatment trajectories. We aimed to evaluate and enhance two existing methods to reconstruct systemic anticancer treatment trajectories. Methods: This study was based on data from 8738 consecutive patients with solid tumors treated in the North Denmark Region between 2009 and 2019. Two approaches found in the literature as well as two new approaches were applied to the DNPR data. All methods relied on time intervals between two consecutive drug administrations to determine if they belonged to the same treatment line. MedOnc, a local dataset from the Department of Oncology, Aalborg University Hospital was used as a reference. To evaluate the performance of each method, F1-scores were calculated after matching the lines identified in both datasets. We used three different matching strategies: stringent matching, loose matching, and matching based on line numbers, controlling for overfitting. Results: Overall, the two new approaches outperformed the simpler and best performing of the two existing methods, with F1-scores of 0.47 and 0.45 vs 0.44 for stringent matching and 0.84 and 0.83 vs 0.82 for loose matching. Nevertheless, only one of the new methods outperformed the existing simpler method when matching on the number of lines (0.73 vs 0.72). Large differences were seen by cancer site, especially for the stringent and line number matchings. Performances were relatively stable by calendar year. Conclusion: The high F1-scores for the new methods confirm that they should be generally preferred to reconstruct systemic anticancer treatment trajectories using the DNPR.

Urinary Prostaglandin E2 Excretion and the Risk of Cardiovascular and Kidney Disease.

BACKGROUND: Inhibition of prostaglandin synthesis by nonsteroidal anti-inflammatory drugs is associated with cardiovascular mortality and kidney disease. This study hypothesizes that urinary prostaglandin E2 (PGE2) and PGE2 metabolite (PGEM) excretions are markers of cardiovascular and kidney health, because they reflect both systemic and kidney-derived PGE2 production. METHODS AND RESULTS: PGE2 and PGEM were measured in spot urine samples from 2291 participants (≥55 years old) of the population-based Rotterdam Study. Urinary PGE2 and PGEM excretions were analyzed using linear regression analyses to identify cross-sectional associations with cardiovascular risk factors and baseline estimated glomerular filtration rate (eGFR). Longitudinal associations with cardiovascular mortality and kidney outcomes (eGFR <60 or <45 mL/min per 1.73 m2 and the composite outcome 40% eGFR loss or kidney failure) were assessed with Cox regression. Urinary PGE2 and PGEM excretions were higher with increasing age, lower eGFR, smoking, diabetes, and albuminuria. A 2-fold higher urinary PGE2 and PGEM excretion was associated with a higher risk of cardiovascular mortality (28 825 patient-years; 160 events; PGE2 hazard ratio [HR], 1.27, [95% CI, 1.06-1.54]; PGEM HR, 1.36 [95% CI, 1.10-1.67]). Higher PGE2 excretions were also associated with a higher risk of incident eGFR <60 mL/min per 1.73 m2 (31 530 person-years; 691 events; HR, 1.13 [95% CI, 1.02-1.25]) with similar HRs for the other kidney outcomes. CONCLUSIONS: Urinary PGE2 and PGEM excretions are novel markers for the presence and progression of cardiovascular and kidney disease. Future studies should address whether these associations are causal and can be targeted to improve cardiovascular and kidney outcomes.

The coverage of influenza vaccination and predictors of influenza non-vaccination in Danish cancer patients: A nationwide register-based cohort study.

BACKGROUND: Influenza vaccination is recommended and provided free-of-charge to Danish citizens aged ≥65 years and to individuals with acquired immunodeficiency. We aimed to estimate influenza vaccination coverage and investigate predictors of influenza non-vaccination in Danish cancer patients. METHODS: A nationwide cohort study of all Danish citizens aged ≥18 years with an incident cancer diagnosis between 2002 and 2017. Using national registries, we assessed information on influenza vaccination and potential predictors of influenza non-vaccination. We estimated adjusted prevalence ratios (aPR) of influenza non-vaccination for patients aged <65 years and ≥65 years. RESULTS: We observed 269,863 patients during 840,876 influenza vaccination seasons. The influenza vaccination coverage was 14 % for cancer patients <65 years and 51 % for those ≥65 years. No influenza vaccination in the previous season was associated with non-vaccination in the current season (<65 years: aPR = 2.75, 95 %CI = 2.71-2.80; ≥65 years: aPR = 5.15, 95 %CI = 5.10-5.21). Haematological cancer patients receiving chemotherapy had lower vaccination prevalence compared with those not receiving chemotherapy. CONCLUSIONS: The influenza vaccination coverage was low among cancer patients. Influenza non-vaccination in the previous season was the strongest predictor of not receiving influenza vaccination in the current season. Haematological cancer patients on current chemotherapy had lower vaccination prevalence than those not currently receiving chemotherapy.

Effect of surgery versus chemotherapy in pancreatic cancer patients: a target trial emulation.

PURPOSE: To estimate the causal effect of surgery vs chemotherapy on survival in patients with T1-3NxM0 pancreatic cancer in a rigorous framework addressing selection bias and immortal time bias. METHODS: We used population-based Danish healthcare registries to conduct a cohort study emulating a hypothetical randomized trial to estimate the absolute difference in survival, comparing surgery with chemotherapy. We included pancreatic cancer patients diagnosed during 2008-2021. Exposure was surgery or chemotherapy initiated within a 16-week grace period after diagnosis. At the time of diagnosis, data of each patient was duplicated; one copy was assigned to the surgery protocol and one copy to the chemotherapy protocol of the hypothetical trial. Copies were censored when the assigned treatment deviated from the observed treatment. To account for informative censoring, uncensored patients were weighted according to confounders. For comparison, we also applied a more conventional analysis using propensity score-based inverse probability weighting. RESULTS: We included 1,744 patients with a median age of 68 years; 73.6% underwent surgery and 18.6% had chemotherapy without surgery. 7.8% received no treatment. The 3-year survival was 39.7% (95% CI 36.7% to 42.6%) after surgery and 22.7% (95% CI: 17.7% to 28.4%) after chemotherapy, corresponding to an absolute difference of 17.0% (95% CI: 10.8% to 23.1%). In the conventional survival analysis, this difference was 23.0% (95% CI: 17.0% to 29.0%). CONCLUSION: Surgery was superior to chemotherapy in achieving long-term survival for pancreatic cancer. The difference comparing surgery and chemotherapy was substantially smaller when using the clone-censor-weight approach than conventional survival analysis.

Beta-blocker use and survival after pancreatic cancer surgery: A nationwide population-based cohort study.

PURPOSE: We examined the association between use of beta-blockers and survival in pancreatic cancer patients after curative-intent surgery. METHODS: Using Danish healthcare registries, we conducted a population-based cohort study of all patients undergoing curative-intent surgery for pancreatic cancer in Denmark 1997-2021. We defined beta-blocker use according to exposure before surgery as current (≤90 days), recent (91-365 days), or former (366-730 days) use, requiring at least one filled prescription. Patients were followed from the date of surgery for up to 5 years. We used Cox regression to compute hazard ratios (HRs) of deaths with 95% confidence intervals (CIs), adjusting for age, sex, year of diagnosis, cardiovascular disease, diabetes, liver disease, alcohol, and smoking. We also conducted an active comparator analysis, where we used angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers as comparators instead of nonusers. RESULTS: We included 2592 patients, of which 16.7% were beta-blocker users. Median survival for the entire population was 24.4 months. Beta-blocker use was associated with increased mortality (adjusted HR: 1.18; 95% CI: 1.04-1.34). This was evident in current (adjusted HR: 1.19; 95% CI: 1.02-1.38) and recent (adjusted HR: 1.29; 95% CI: 1.04-1.59) but not former (adjusted HR: 0.91; 95% CI: 0.64-1.43) users. In the active comparator analysis, the association between beta-blocker exposure and mortality attenuated slightly (adjusted HR: 1.12; 95% CI: 0.93-1.35). CONCLUSIONS: We observed an association between beta-blocker use and increased mortality in patients operated for pancreatic cancer. Findings are likely explained by confounding by indication.

New Horizons: Epidemiology of Obesity, Diabetes Mellitus, and Cancer Prognosis.

The global prevalence of obesity and diabetes mellitus has increased in parallel with increasing cancer incidence, due to environmental and lifestyle factors and population aging. Metabolic diseases are associated with increased cancer risk, so a growing number of patients with cancer have coexistent obesity and/or diabetes mellitus. In this narrative review, we highlight recent evidence on the clinical impact of obesity and diabetes mellitus on the prognosis of prostate, breast, and colorectal cancer, and provide an overview of the underlying mechanisms. There is evidence that obesity is associated with increased risk of recurrence, and all-cause and cancer-specific mortality among adults with prostate, breast, and colorectal cancer. Diabetes mellitus is associated with increased all-cause and cancer-specific mortality for these 3 cancers, beyond any impact of obesity. Evidence also suggests increased risk of colorectal cancer recurrence in patients with diabetes mellitus. The underlying mechanisms are multifactorial and likely include hormonal imbalances and chronic inflammation that promote cancer cell growth. Obesity and diabetes mellitus are associated with increased risk of complications and side effects of cancer treatment. Associated comorbidities such as impaired kidney function, cardiovascular disease, and neuropathies may preclude the use of guideline cancer treatment and are competing causes of death. Cancer patients with metabolic diseases require a designated clinical program and a multidisciplinary approach involving oncologists, endocrinologists, surgeons, nutritionists, and physiotherapists, to ensure coordinated and optimized patient care.

Biomarkers predictive of a response to extended endocrine therapy in breast cancer: a systematic review and meta-analysis.

PURPOSE: Extension of adjuvant endocrine therapy beyond five years confers only modest survival benefit in breast cancer patients and carries risk of toxicities. This systematic review investigates the role of biomarker tests in predicting the clinical response to an extension of endocrine therapy. METHODS: We searched Ovid MEDLINE, Ovid Embase, Global Index Medicus, and the Cochrane Central Register of Controlled Trials using an iterative approach to identify full-text articles related to breast cancer, endocrine therapy, and biomarkers. RESULTS: Of the 1,217 unique reports identified, five studies were deemed eligible. Four investigated the Breast Cancer Index (BCI) assay in three distinct study populations. These studies consistently showed that BCI score was predictive of response to extended endocrine therapy among 1,946 combined patients, who were predominately non-Hispanic white and postmenopausal. CONCLUSIONS: Evidence in the setting of predictive tests for extended endocrine therapy is sparse. Most relevant studies investigated the use of BCI, but these study populations were largely restricted to a single age, race, and ethnicity group. Future studies should evaluate a variety of biomarkers in diverse populations. Without sufficient evidence, physicians and patients face a difficult decision in balancing the benefits and risks of endocrine therapy extension.

Obesity and Risk of Recurrence in Patients With Breast Cancer Treated With Aromatase Inhibitors.

Importance: Clinical studies confirm that obesity is a risk factor for recurrence in postmenopausal women with hormone receptor-positive (HR+) breast cancer. Evidence suggests that women with obesity do not obtain similar protection from aromatase inhibitors as women with healthy weight. Objective: To examine the associations of body mass index (BMI) with recurrence. Design, Setting, and Participants: The cohort study was conducted using data from the Danish Breast Cancer Group and enrolled postmenopausal women diagnosed with stage I to III HR+ breast cancer from 1998 through 2016. Data analysis was conducted from November 2022 to April 2023. Exposures: BMI was classified as (1) healthy weight (18.5-24.9), (2) overweight (25.0-29.9), (3) obesity (30.0-34.9), and (4) severe obesity (≥35.0) using the World Health Organization guidelines. Healthy weight was considered the reference group in statistical analyses. Main Outcomes and Measures: Follow-up began 6 months after breast cancer surgery and continued until the first event of recurrence, contralateral breast cancer, new primary malignant neoplasm, death, emigration, end of clinical follow-up at 10 years, or September 25, 2018. Cox regression was used to estimate crude and adjusted hazard ratios with 95% CIs, adjusting for patient, tumor, and treatment characteristics. Results: A total of 13 230 patients (median [IQR] age at diagnosis, 64.4 [58.6-70.2] years) with information on BMI were enrolled. There were 1587 recurrences with a median (IQR) potential estimated follow-up of 6.2 (3.6-8.5) years. Multivariable analyses revealed increased recurrence hazards associated with obesity (adjusted hazard ratio, 1.18 [95% CI, 1.01-1.37]) and severe obesity (adjusted hazard ratio, 1.32 [95% CI, 1.08-1.62]) vs patients with healthy weight. Patients with overweight had a greater risk, but the results were not statistically significant (adjusted hazard ratio, 1.10 [95% CI, 0.97-1.24]). Conclusions and Relevance: In this study, obesity was associated with an increased risk of breast cancer recurrence among postmenopausal patients with HR+ early-stage breast cancer treated with aromatase inhibitors. Physicians should be aware of the significance of obesity on breast cancer outcomes to secure optimal treatment benefit in all patients.

Breast cancer and incidence of type 2 diabetes mellitus: a systematic review and meta-analysis.

PURPOSE: Breast cancer and its treatments may increase the risk of type 2 diabetes (T2D). We conducted a systematic review and meta-analysis to investigate the association between breast cancer and the incidence of T2D overall, and according to breast cancer treatments. METHODS: We searched PubMed, Embase and references of relevant papers for studies on breast cancer, breast cancer treatment, and subsequent T2D risk. Using random-effects models, we calculated effect estimates and associated 95% confidence intervals of the association between breast cancer, adjuvant breast cancer treatments (i.e., endocrine therapy (tamoxifen, aromatase inhibitors, and combined) and chemotherapy), and subsequent T2D. We used funnel plots to assess publication bias. RESULTS: Among 15 eligible studies, 10 reported on T2D risk after breast cancer, chemotherapy, or endocrine therapy; five studies investigated more than one association. Compared with patients without breast cancer, those with breast cancer and those who received any endocrine therapy had elevated risk of incident T2D (EE = 1.23, 95% CI = 1.13-1.33 and EE = 1.23, 95% CI = 1.16-1.32, respectively). Among breast cancer patients only, the risk of T2D was higher for those who received tamoxifen compared with those who did not receive tamoxifen (EE = 1.28, 95% CI = 1.18-1.38). Due to few studies, analyses investigating T2D risk after treatment with aromatase inhibitors or chemotherapy were inconclusive. CONCLUSION: Our findings suggest an elevated risk of T2D in breast cancer survivors, particularly after tamoxifen therapy. Further research is needed to determine the impact of aromatase inhibitors, and chemotherapy on the incidence of T2D after breast cancer.

Obesity and breast cancer prognosis: pre-diagnostic anthropometric measures in relation to patient, tumor, and treatment characteristics.

PURPOSE: Examine the association between obesity and clinical outcomes in early breast cancer and assess if patient, tumor, and treatment characteristics modify such associations in Malmö Diet and Cancer Study patients (MDCS). METHODS: The MDCS enrolled 17,035 Swedish women from 1991 to 1996. At enrollment, participants' body mass index (BMI), waist circumference and body fat percentage measures were collected. We identified all female MDCS participants with invasive breast cancer from 1991 to 2014. Follow-up began at breast cancer diagnosis and ended at breast cancer recurrence (BCR), death, emigration, or June 8, 2020. The World Health Organization guidelines were used to classify BMI, waist circumference, and body fat percentage into three categories of healthy weight, overweight, and obesity. We fit Cox regression models to compute adjusted hazard ratios (HRs) with 95% confidence intervals (CI) of BCR according to body composition. To evaluate effect measure modification, we stratified Cox models by patient, tumor, and treatment characteristics. RESULTS: In total, 263 BCRs were diagnosed over 12,816 person-years among 1099 breast cancer patients with a median follow-up of 11.1 years. Obesity according to BMI (HR = 1.44 [95%CI 1.00-2.07]), waist circumference (HR = 1.31 [95%CI 0.98-1.77]), and body fat percentage (HR = 1.41 [95%CI 1.02-1.98]) was associated with increased risk of BCR compared with healthy weight. Obesity was stronger associated with BCR in patients with low socioeconomic position (HR = 2.55 [95%CI 1.08-6.02]), larger tumors > 20 mm (HR = 2.68 [95%CI 1.42-5.06]), estrogen-receptor-negative breast cancer (HR = 3.13 [95%CI 1.09-8.97]), and with adjuvant chemotherapy treatment (HR = 2.06 [95%CI 1.08-4.31]). CONCLUSION: Higher pre-diagnostic BMI, waist circumference, and body fat percentage was associated with increased risk of BCR. The association between obesity and BCR appears dependent on patient, tumor, and treatment characteristics.

Biomarker expression and survival in patients with non-small cell lung cancer receiving adjuvant chemotherapy in Denmark.

INTRODUCTION: Programmed cell death ligand-1 (PD-L1) expression may help identify patients with non-small cell lung cancer (NSCLC) who would benefit from immunotherapy. We assessed PD-L1 expression, and epidermal growth factor receptor (EGFR) and V-Ki-Ras2 Kirsten rat sarcoma (KRAS) mutations in NSCLC patients receiving adjuvant chemotherapy. METHODS: Data for stage IB/II/IIIA NSCLC patients (diagnosed: 2001-2012) were retrieved from Danish population-based registries. Tumor tissue samples were tested for PD-L1 expression using VENTANA PD-L1 (SP263) Assay in tumor cells (TC) at ≥25% cutoff and immune cells (IC) at ≥1% and ≥25% cutoffs. KRAS and EGFR mutations were tested using PCR-based assays. Follow-up began 120 days after diagnosis until death/emigration/January 1, 2015, whichever came first. Using Cox proportional hazard regression, hazard ratios (HRs) were computed for overall survival (OS) for each biomarker, adjusting for age, sex, histology, comorbidities, and tissue specimen age. RESULTS: Among 391 patients identified, 40.4% had stage IIIA disease, 49.9% stage II, and 8.7% stage IB. PD-L1-TC was observed in 38% of patients, EGFR mutations in 4%, and KRAS mutations in 29%. KRAS mutations were more frequent among patients with PD-L1 TC≥25% versus TC<25% (37% versus 24%). OS was not associated with PD-L1 TC≥25% versus TC<25% (stage II: adjusted HR = 1.15 [95% confidence interval: 0.66-2.01]; stage IIIA: 0.72 [0.44-1.19]). No significant association was observed with OS and PD-L1-IC ≥1% and ≥25%. EGFR and KRAS mutations were not associated with a prognostic impact. CONCLUSION: A prognostic impact for NSCLC patients receiving adjuvant chemotherapy was not associated with PD-L1 expression, or with EGFR and KRAS mutations.

Breast cancer, breast cancer-directed radiation therapy and risk of hypothyroidism: A systematic review and meta-analysis.

OBJECTIVE: Breast cancer and breast cancer-directed radiation therapy (RT) may increase the risk of late effects, such as hypothyroidism. We conducted a systematic review and meta-analysis to investigate the association between breast cancer, RT, and risk of hypothyroidism in breast cancer survivors. METHODS: Through February 2022, we searched PubMed, EMBASE, and references of relevant articles, to identify papers on breast cancer and breast cancer-directed RT and subsequent risk of hypothyroidism. Articles were screened by title and abstract and reviewed for eligibility. We used a pre-formed data extraction sheet and identified key design elements that could potentially introduce bias. The main outcome was the confounder-adjusted relative risk (RR) of hypothyroidism in breast cancer survivors versus women without breast cancer, and in breast cancer survivors according to the receipt of RT to the supraclavicular lymph nodes. We used a random-effects model to calculate pooled RRs and associated 95% confidence intervals (95% CI). RESULTS: From 951 papers screened by title and abstract, 34 full-text papers were reviewed for eligibility. We included 20 studies published between 1985 and 2021-19 were cohort studies. Compared with women without breast cancer, the pooled RR of hypothyroidism in breast cancer survivors was 1.48 (95% CI: 1.17, 1.87), with highest risk associated with RT to the supraclavicular region (RR = 1.69, 95% CI: 1.16, 2.46). The most important limitations of the studies were small sample size yielding estimates with low precision, and lack of data on potential confounders. CONCLUSION: Breast cancer and radiation therapy to the supraclavicular lymph nodes is associated with an increased risk of hypothyroidism.

Identifying Recurrences Among Non-Metastatic Colorectal Cancer Patients Using National Health Data Registries: Validation and Optimization of a Registry-Based Algorithm in a Modern Danish Cohort.

Purpose: Colorectal cancer (CRC) recurrence is not routinely recorded in Danish health data registries. Here, we aimed to revalidate a registry-based algorithm to identify recurrences in a contemporary cohort and to investigate the accuracy of estimating the time to recurrence (TTR). Patients and Methods: We ascertained data on 1129 patients operated for UICC TNM stage I-III CRC during 2012-2017 registered in the CRC biobank at the Department of Molecular Medicine, Aarhus University Hospital, Denmark. Individual-level data were linked with data from the Danish Colorectal Cancer Group database, Danish Cancer Registry, Danish National Registry of Patients, and Danish Pathology Registry. The algorithm identified recurrence based on diagnosis codes of local recurrence or metastases, the receipt of chemotherapy, or a pathological tissue assessment code of recurrence more than 180 days after CRC surgery. A subgroup was selected for validation of the algorithm using medical record reviews as a reference standard. Results: We found a 3-year cumulative recurrence rate of 20% (95% CI: 17-22%). Manual medical record review identified 80 recurrences in the validation cohort of 522 patients. The algorithm detected recurrence with 94% sensitivity (75/80; 95% CI: 86-98%) and 98% specificity (431/442; 95% CI: 96-99%). The positive and negative predictive values of the algorithm were 87% (95% CI: 78-93%) and 99% (95% CI: 97-100%), respectively. The median difference in TTR (TTRMedical_chart-TTRalgorithm) was -8 days (IQR: -21 to +3 days). Restricting the algorithm to chemotherapy codes from oncology departments increased the positive predictive value from 87% to 94% without changing the negative predictive value (99%). Conclusion: The algorithm detected recurrence and TTR with high precision in this contemporary cohort. Restriction to chemotherapy codes from oncology departments using department classifications improves the algorithm. The algorithm is suitable for use in future observational studies.

The carcinogenicity of opium consumption: a systematic review and meta-analysis.

The carcinogenicity of opium consumption was recently evaluated by a Working Group convened by the International Agency for Research on Cancer (IARC). We supplement the recent IARC evaluation by conducting an extended systematic review as well as a quantitative meta-analytic assessment of the role of opium consumption and risk for selected cancers, evaluating in detail various aspects of study quality on meta-analytic findings. We searched the published literature to identify all relevant studies on opium consumption and risk of selected cancers in humans through 31 October, 2022. Meta-relative risks (mRRs) and associated 95% confidence intervals (CIs) were estimated using random-effects models for studies of cancer of the urinary bladder, larynx, lung, oesophagus, pancreas, and stomach. Heterogeneity among studies was assessed using the I2 statistic. We assessed study quality and conducted sensitivity analyses to evaluate the impact of potential reverse causation, protopathic bias, selection bias, information bias, and confounding. In total, 2 prospective cohort studies and 33 case-control studies were included. The overall pooled mRR estimated for 'ever or regular' versus 'never' use of opium ranged from 1.50 (95% CI 1.13-1.99, I2 = 0%, 6 studies) for oesophageal cancer to 7.97 (95% CI 4.79-13.3, I2 = 62%, 7 studies) for laryngeal cancer. Analyses of cumulative opium exposure suggested greater risk of cancer associated with higher opium consumption. Findings were robust in sensitivity analyses excluding studies prone to potential methodological sources of biases and confounding. Findings support an adverse association between opium consumption and cancers of the urinary bladder, larynx, lung, oesophagus, pancreas and stomach.

The impact of single nucleotide polymorphisms on return-to-work after taxane-based chemotherapy in breast cancer.

PURPOSE: Breast cancer treatment is associated with adverse effects, which may delay return-to-work. Single nucleotide polymorphisms (SNPs) may influence the risk and severity of treatment toxicities, which in turn could delay return-to-work. We examined the association of 26 SNPs with return-to-work in premenopausal women with breast cancer. METHODS: Using Danish registries, we identified premenopausal women diagnosed with non-distant metastatic breast cancer during 2007‒2011, assigned adjuvant combination chemotherapy including cyclophosphamide and docetaxel. We genotyped 26 SNPs in 20 genes (ABCB1, ABCC2, ABCG2, CYP1A1, CYP1B1, CYP3A, CYP3A4, CYP3A5, GSTP1, SLCO1B1, SLCO1B3, ARHGEF10, EPHA4, EPHA5, EPHA6, EPHA8, ERCC1, ERCC2, FGD4 and TRPV1) using TaqMan assays. We computed the cumulative incidence of return-to-work (defined as 4 consecutive weeks of work) up to 10 years after surgery, treating death and retirement as competing events and fitted cause-specific Cox regression models to estimate crude hazard ratios (HRs) and 95% confidence intervals (CIs) of return-to-work. We also examined stable labor market attachment (defined as 12 consecutive weeks of work). RESULTS: We included 1,964 women. No associations were found for 25 SNPs. The cumulative incidence of return-to-work varied by CYP3A5 rs776746 genotype. From 6 months to 10 years after surgery, return-to-work increased from 25 to 94% in wildtypes (n = 1600), from 17 to 94% in heterozygotes (n = 249), and from 7 to 82% in homozygotes (n = 15). The HR showed delayed return-to-work in CYP3A5 rs776746 homozygotes throughout follow-up (0.48, 95% CI 0.26, 0.86), compared with wildtypes. Estimates were similar for stable labor market attachment. CONCLUSION: Overall, the SNPs examined in the study did not influence return-to-work or stable labor market attachment after breast cancer in premenopausal women. Our findings did suggest that the outcomes were delayed in homozygote carriers of CYP3A5 rs776746, though the number of homozygotes was low.