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Jakob H Viuff,1 Ilse Vejborg,2 Walter Schwartz,3 Martin Bak,4 Ellen M Mikkelsen1 1Department of Clinical Epidemiology, Aarhus University Hospital,Aarhus N 8200, Denmark; 2Department of Radiology, University Hospital of Copenhagen Rigshospitalet, Copenhagen 2100, Denmark; 3Department of Radiology, Odense University Hospital, Odense C 5000, Denmark; 4Department of Pathology, Sydvestjysk Sygehus, Esbjerg 6700, DenmarkCorrespondence: Jakob H ViuffVirus, Lifestyle and Genes, Danish Cancer Society Research Center, Strandboulevarden 49, Copenhagen 2100, DenmarkEmail jviuff@cancer.dkPurpose: In this cross-sectional study, we evaluated the association between morbidity and participation in the prevalence round of the Danish national mammography screening program.Patients and Methods: Morbidity was assessed by the Charlson Comorbidity Index (CCI) score (0, 1– 2, and ≥ 3) and by 19 individual diagnoses. We retrieved data on participation from The Danish Quality Database of Mammography Screening and on diagnoses from The Danish National Patient Registry. We estimated prevalence proportion ratios (PR) with 95% confidence intervals (CI).Results: In total, 519,009 (79.8%) women participated in the first national breast cancer screening round. Relative to women with a CCI score of 0, the adjusted PRs were 0.96 (95% CI: 0.95– 0.96) for a CCI score of 1– 2 and 0.80 (95% CI: 0.79– 0.81) for a CCI score of ≥ 3. Compared with no disease, the PRs for a diagnosis of the most prevalent, but less severe diseases, chronic pulmonary disease, cerebrovascular disease, diabetes I and II were 0.93 (95% CI: 0.93– 0.94), 0.96 (95% CI: 0.94– 0.96), and 0.96 (95% CI: 0.95– 0.97), respectively. Among women with low prevalent, but most severe diseases, the PRs were 0.69 (95% CI: 0.60– 0.81) for AIDS and 0.73 (95% CI: 0.70– 0.76) for metastatic solid tumor.Conclusion: Women with a high CCI score or one severe chronic condition are less likely to participate in breast cancer screening compared to women without disease. However, these women account for a small proportion of all non-participating women. Thus, it might be most beneficial to maximize breast cancer screening participation in women with less severe although more common morbidities.Keywords: mass screening, mammography, breast cancer, patient compliance, morbidity and comorbidity

Purpose: Although some reproductive and metabolic characteristics of polycystic ovary syndrome (PCOS) are known risk factors for breast cancer, the evidence regarding a potential association between PCOS and breast cancer is scarce. In this population-based cohort study including all 1,719,452 women born in Denmark between 1940 and 1993, we investigated the association between PCOS and breast cancer., Methods: PCOS diagnoses, cancer diagnoses, covariates, migrations, and vital status were all obtained from national population and health registers. Hazard ratios (HR) and 95% confidence intervals (CI) for breast cancer overall and for histological subtypes separately were calculated based on adjusted cox proportional hazards models., Results: During a median follow-up of 26 years, 63,078 women were diagnosed with breast cancer. We found an increased risk of breast cancer overall among women with PCOS compared with women without PCOS (HR: 1.21, 95% CI 1.02-1.44). In analyses stratified for menopausal status, the increased risk was restricted to postmenopausal women (HR: 1.63, 95% CI 1.23-2.15). The results for ductal and lobular histological subtypes analyses separately resembled those observed for breast cancer overall., Conclusion: This is the first study to report an increased risk of breast cancer among women with a history of PCOS. The increased risk was seemingly confined to postmenopausal women. Our results therefore contribute to an increased knowledge of the etiology of breast cancer, but our findings should be further confirmed in other large cohort studies with an appropriately long follow-up period., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: To investigate the potential lead time bias of the evaluation model (extended follow-up for women diagnosed with breast cancer) used to evaluate mammography screening in a recent Danish study. This model was compared with two traditional models., Methods: We retrieved data on women diagnosed with breast cancer in each county of Norway from 1986 to 2016. In a population-based open cohort study, the change in incidence-based mortality (IBM) was estimated by relative rate ratios comparing a screening period with a historical period for each of three age groups: women eligible for screening and younger and older ineligible women. We applied the evaluation model, and for comparison two traditional IBM models from a recent Norwegian study: one without extended follow-up and no possibility of lead time bias and one with extended follow-up irrespective of diagnosis, possibly diluting any screening effect., Results: The evaluation model estimated an extra 11% reduction in breast cancer mortality among the screening eligible relative to ineligible women. However, this result could largely be ascribed to lead time bias inflated by overdiagnosis and a decreasing mortality from other causes among eligible women. A reduction in breast cancer mortality was observed for both eligible and younger and older ineligible women across models, and relative rate ratios close to 1 were obtained using the two traditional IBM models, indicating no effect of screening on breast cancer mortality., Conclusions: Two models without lead time bias found no reduction in breast cancer mortality, whereas the evaluation model estimated a reduction attributable to lead time bias ., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Most previous studies found an elevated risk of endometrial cancer among women with polycystic ovary syndrome (PCOS). However, these had highly varying methods for ascertainment of PCOS diagnoses and limitations such as few exposed women and short follow-up. In this cohort study, we investigated the association between PCOS and endometrial cancer among women born in Denmark between January 1, 1940, and December 31, 1993 (n = 1 719 121). Data in this study, including PCOS and endometrial cancer diagnoses and covariates, were derived from nationwide registers. We used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% CIs. A total of 7862 endometrial cancer cases were identified during 23.7 years of follow-up (IQR, 37.7-61.9). We found an increased risk of endometrial cancer among women with PCOS compared with women without PCOS (HR = 3.02; 95% CI, 2.03-4.49). The risk was increased for premenopausal women (HR = 5.82; 95% CI, 3.64-9.30), whereas no marked association was seen for postmenopausal women. However, for postmenopausal women, results were limited by few cases and young age at the end of follow-up. Mounting evidence of an increased risk for endometrial cancer among women with PCOS reinforces the need for prevention and early detection. This article is part of a Special Collection on Gynecological Cancers., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Results from previous studies examining the association between fertility treatment and borderline ovarian tumors are inconsistent. The aim of this study was to investigate the association between fertility treatment and borderline ovarian tumors in a cohort of infertile women., Methods: This cohort study was based on the Danish Infertility Cohort and included all infertile women aged 20-45 years living in Denmark between 1 January 1995 and 31 December 2017 (n = 146,891). Information on use of fertility drugs, borderline ovarian tumors and cancer diagnoses, covariates, emigration, and vital status was obtained by linkage to national registers. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) with adjustment for potential confounders for overall borderline ovarian tumors and for serous- and mucinous borderline ovarian tumors separately., Results: During a median 11.3 years of follow-up, 144 women developed a borderline ovarian tumor. No marked associations between ever use of clomiphene citrate, gonadotropins, gonadotropin-releasing hormone receptor modulators, human chorionic gonadotropin or progesterone and borderline ovarian tumors were observed, neither overall nor for serous and mucinous borderline ovarian tumors analysed separately. Further, no clear associations with borderline ovarian tumors were found according to cumulative dose, time since first use or parity status for any fertility drugs., Conclusions: No marked associations between use of fertility drugs and borderline ovarian tumors were observed. However, the cohort's relatively young age at end of follow-up emphasizes the importance of extending the follow-up period for women who have used fertility drugs., Competing Interests: Declaration of competing interest Bugge Nøhr received grants from Gedeon Richter Nordics AB, IBSA Nordic APS, Merck KGAA, consulting fees from Ferring Pharmaceuticals A/S, honoraria for lectures from Organon Denmark ApS and support for meeting attendance from Gedeon Richter Nordics AB. The remaining authors have no conflict of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: In utero exposure to maternal cancer and cancer treatment might influence the child's cognitive development. This study investigated if exposure to maternal cancer during fetal life impacted school performance and educational achievement as adults., Methods: This nationwide retrospective cohort study identified all live-born children in Denmark between January 1978 and December 2013. Exposure was defined as maternal cancer diagnosis during pregnancy. Four partly overlapping birth cohorts were constructed depending on the outcome of interest: (1) receiving special educational support for birth years 2001-2013; (2) grade point average (GPA) at the final exams after 10th grade for 1986-2003; (3) educational achievement at 20 years for 1978-1998; and (4) education at 30 years for 1978-1988. Logistic and linear models were adjusted for birth year, maternal age, maternal education and maternal death., Results: The estimated probability of receiving special educational support was similar in the exposed group and the reference (adjusted OR 0.96; 95% CI 0.46 to 1.77, non-significant). The GPA did not statistically differ (0.13 grade points; 95% CI -0.18 to 0.45, non-significant). The achieved educational levels were similar for the exposed group and the reference at 20 years, with an adjusted OR of 1.07 (95% CI 0.82 to 1.40) for low versus medium educational level, and at 30 years with an adjusted OR of 0.73 (95% CI 0.35 to 1.50) for low versus high educational level and of 1.07 (95% CI 0.66 to 1.72) for medium versus high educational level., Conclusion: Our findings did not indicate poorer performance in compulsory school nor impairment of adult educational achievement after exposure to maternal cancer in utero., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

An association between polycystic ovary syndrome (PCOS) and epithelial ovarian tumors is biologically plausible as conditions inherent to PCOS such as excessive androgenic hormones, reproductive factors and obesity are also risk factors for these hormone-sensitive tumors. However, previous studies have showed conflicting results and have various methodological limitations. This population-based cohort study investigates the association between PCOS and epithelial ovarian tumors and includes all women born in Denmark between January 1, 1940 and December 31, 1993 (n = 1 719 304). PCOS diagnoses, ovarian cancer and borderline ovarian tumor diagnoses, covariates, migration and vital status were obtained from the Danish national registers. Adjusted cox proportional hazard regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CI) for epithelial ovarian cancer and for borderline ovarian tumors overall as well as for histological subtypes separately. During median 26 years of follow-up we identified 6490 women with ovarian cancer and 2990 women with borderline ovarian tumors. Overall, we observed no marked associations between a diagnosis of PCOS and overall epithelial ovarian cancer or overall epithelial borderline ovarian tumors, irrespective of time since diagnosis. However, we found an increased risk of ovarian cancer among postmenopausal women with PCOS (HR 2.28 95% CI 1.02-5.09) and an increased risk of serous borderline ovarian tumors (HR 2.34 95% CI 1.21-4.53) in women with PCOS compared with women without PCOS. Importantly, low statistical precision is a crucial limitation of our study and in previous studies and larger studies with longer follow-up are therefore warranted., (© 2023 UICC.)

Background: More evidence is needed to substantiate current recommendations about removing ovaries during hysterectomy for benign conditions., Objective: To compare long-term outcomes in women with and without bilateral salpingo-oophorectomy (BSO) during hysterectomy for benign conditions., Design: Emulated target trial using data from a population-based cohort., Setting: Women in Denmark aged 20 years or older during 1977 to 2017., Participants: 142 985 women with hysterectomy for a benign condition, 22 974 with BSO and 120 011 without., Intervention: Benign hysterectomy with or without BSO., Measurements: The primary outcomes were overall hospitalization for cardiovascular disease (CVD), overall cancer incidence, and all-cause mortality through December 2018., Results: Compared with women without BSO, women with BSO who were younger than 45 years at surgery had a higher 10-year cumulative risk for hospitalization for CVD (risk difference [RD], 1.19 percentage points [95% CI, 0.09 to 2.43 percentage points]). Women with BSO had a higher 10-year cumulative risk for cancer for ages 45 to 54 years (RD, 0.73 percentage point [CI, 0.05 to 1.38 percentage points]), 55 to 64 years (RD, 1.92 percentage points [CI, 0.69 to 3.25 percentage points]), and 65 years or older (RD, 2.54 percentage points [CI, 0.91 to 4.25 percentage points]). Women with BSO had higher 10-year mortality in all age groups, although the differences were statistically significant only for ages 45 to 54 years (RD, 0.79 percentage point [CI, 0.27 to 1.30 percentage points]). The mortality at 20 years was inconsistent with that at 10 years in women aged 65 years or older., Limitation: Age was a proxy for menopausal status., Conclusion: The authors find that these results support current recommendations for conserving ovaries in premenopausal women without a high risk for ovarian cancer and suggest a cautious approach in postmenopausal women., Primary Funding Source: The Danish Cancer Society's Scientific Committee and the Mermaid Project., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M22-1628.

Purpose: To evaluate whether previous ovarian removal concomitant with benign hysterectomy improves prognosis in a cohort of women with breast cancer., Methods: In this nationwide register-based cohort study, risk of recurrence and mortality were examined in 4563 women with invasive breast cancer and previous bilateral salpingo-oophorectomy (BSO) concomitant with benign hysterectomy, during 1977-2018. Comparing with benign hysterectomy alone, hazard ratios (HRs) and 95% confidence intervals (CIs) were evaluated by Cox-proportional hazards regression models. Analyses were stratified on age at hysterectomy as a proxy for menopausal status (< 45, 45-54 and ≥ 55 years); tumor characteristics, estrogen receptor (ER)-status, and use of hormone therapy (HT) were included in multivariable models., Results: Compared with hysterectomy alone, premenopausal (< 45 years) BSO at benign hysterectomy was associated with an age and calendar period adjusted HR of 1.48 (95% CI 0.83-2.65) for breast cancer recurrence within 10 years of follow-up, a HR of 1.07 (95% CI 0.66-1.72) for overall mortality after breast cancer, and a HR of 0.59 (95% CI 0.26-1.32) for breast cancer-specific mortality. The corresponding HRs for postmenopausal (≥ 55 years) BSO at benign hysterectomy were 1.51 (95% CI 0.73-3.12) for recurrences, 1.34 (95% CI 0.74-2.44) for overall mortality, and 1.78 (95% CI 0.74-4.30) for breast cancer mortality. Adjusting for tumor characteristics, ER-status and HT did not alter the results., Conclusion: Results from this cohort study did not indicate an improvement in breast cancer prognosis when removing the ovaries at benign hysterectomy prior to the cancer diagnosis., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: In utero exposure to maternal cancer and cancer treatment might influence the child's short- and long-term health and development. The objective of the study was to investigate short- and long-term somatic and psychiatric outcomes in children exposed to maternal cancer in utero., Methods: This nationwide cohort study identified all liveborn children in Denmark between January 1978 and December 2018. Exposure was defined as maternal cancer diagnosis during pregnancy, and in a subgroup analysis, exposure to chemotherapy in utero. The main outcomes of interest were overall mortality, somatic diagnoses, and psychiatric diagnoses identified in the National Health Registers. Follow-up started at birth and ended at an event, death, emigration, or end of 2018. Hazard ratios of end points adjusted for potential confounders were estimated using Cox regression analysis., Results: Of 2,526,163 included liveborn children, 690 (0.03%) were exposed to maternal cancer in utero. Compared with unexposed fetuses, children exposed in utero had no higher overall mortality, adjusted hazard ratio 0.8 (95% CI, 0.4 to 1.5), nor increased risk of congenital malformations, overall somatic or psychiatric disease. During the period 2002-2018, of 378 (0.03%) children exposed to cancer in utero, 42 (12.5%) were exposed to chemotherapy. Among these 42 children, in utero exposure to chemotherapy was not associated with selected somatic diseases nor to congenital malformations when compared with in utero exposure to maternal cancer without chemotherapy., Conclusion: Overall, findings did not indicate excess risk of mortality or severe morbidity among children exposed to cancer in utero. Fetal exposure to chemotherapy was not associated with adverse health outcomes in childhood.

Objective: To study the association between use of fertility drugs and colorectal cancer among women with infertility., Design: Population-based cohort study., Setting: Not applicable., Patient(s): The study cohort was obtained from the Danish Infertility Cohort and consisted of all women with infertility aged 20-45 years living in Denmark during 1995-2017., Intervention(s): Information on the use of specific types of fertility drugs, colorectal cancer diagnoses, covariates, and vital status were obtained from the Danish Infertility Cohort and Danish national registers., Main Outcome Measure(s): Cox proportional hazard models adjusted for potential confounders were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for colorectal cancer overall and rectal and colon cancer separately., Results(s): Among 148,036 women in the final study cohort, 205 women were diagnosed with colorectal cancer. Ever use of clomiphene citrate (CC) was associated with a lower rate of colorectal cancer (unadjusted HR, 0.67; 95% CI, 0.51-0.89; adjusted HR, 0.68; 95% CI, 0.50-0.93). However, the lower rate was only seen among women who first used CC >8 years ago (unadjusted HR, 0.56; 95% CI, 0.41-0.76; adjusted HR, 0.52; 95% CI, 0.36-0.75). No marked associations were found between the use of any of other types of fertility drugs and colorectal cancer. The results for colon and rectal cancer analyzed separately were similar, except for a suggestion of a decreased risk of rectal cancer associated with the use of gonadotropins (adjusted HR, 0.46; 95% CI, 0.20-1.08)., Conclusion(s): Among women with infertility, the use of most types of fertility drugs was not associated with colorectal cancer. However, CC may decrease the risk of colorectal cancer and gonadotropins might decrease the risk of rectal cancer, but we cannot rule out that these findings may be more related to the underlying conditions in these women or are chance findings. Consequently, the results from this study should be investigated further in large epidemiological studies., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate the obstetrical management of cancer in pregnancy and to determine adverse pregnancy and neonatal outcomes., Design: A nationwide cohort study., Setting and Population: We included all pregnancies (n = 4 071 848) in Denmark from 1 January 1973 to 31 December 2018., Methods: Exposure was defined as pregnancies exposed to maternal cancer (n = 1068). The control group comprised pregnancies without cancer. The groups were compared using logistic regression analysis and adjusted for potential confounders., Main Outcome Measures: The outcomes were induced abortion, preterm birth and adverse neonatal outcomes., Results: More women with cancer in pregnancy, as compared with the control group, experienced induced abortion (24.8% vs. 20.0%); first-trimester induced abortion adjusted odds ratio (aOR) 3.5 (95% confidence interval [CI] 2.7-4.5), second-trimester induced abortion; aOR 8.8 (95% CI 6.3-12.3), planned preterm birth (11.8% vs. 1.3%); aOR 10.8 (95% CI 8.0-14.6) and planned preterm birth at <32 gestational weeks; aOR 16.3 (95% CI 8.3-31.7). Neonates born to mothers with cancer in pregnancy had a higher risk of respiratory distress syndrome; aOR 3.5 (95% CI 2.8-4.4), low birthweight; aOR 3.8 (95% CI 3.1-4.8), admission to neonatal intensive care unit for >7 days; aOR 5.1 (95% CI 3.9-6.6), neonatal infection; aOR 1.8 (95% CI1.1-3.1) and neonatal mortality; aOR 4.7 (95% CI 2.7-8.2), but not of SGA; aOR 1.0 (95% CI 0.6-1.5) and malformations; 1.2 (95% CI 0.9-1.7)., Conclusion: Cancer in pregnancy increases the risk of induced abortion and planned premature birth. Neonates born to mothers with cancer in pregnancy had an increased risk of neonatal morbidity and mortality, presumably due to prematurity., Tweetable Abstract: Cancer in pregnancy is associated with an increased risk of premature birth leading to adverse neonatal outcomes., (© 2022 John Wiley & Sons Ltd.)

Introduction: Pregnancy rarely coincides with breast cancer, but when it does, uncertainties remain about how survival is affected. In a nation-wide study, we investigated survival in women diagnosed with breast cancer during pregnancy., Materials and Methods: Through health registries, we identified women with breast cancer at ages 15-44 years from 1973-2016 in Denmark and included 156 who were pregnant at diagnosis and 11,110 who were not. We compared overall mortality in pregnant and non-pregnant women using multivariate Cox regression stratified by time since cancer: <2 and ≥2 years., Results: During the first 2 years after diagnosis, the hazard ratio of overall death was 2.28 (95% CI: 1.48-3.52) for pregnant versus non-pregnant breast cancer patients after adjustment for age and calendar period and 1.62 (95% CI: 1.05-2.50) after further adjustment for extent of disease. Adjusting for additional tumor characteristics, the hazard ratio was still significantly increased. Beyond the first 2 years, there was no excess mortality., Conclusion: Our study identifies the early period after breast cancer as a period of particular interest in future studies on survival after breast cancer in pregnancy. We found no evidence that survival is affected by pregnancy when 2 or more years have passed since diagnosis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Asthma and molar incisor hypomineralization (MIH) are common diseases among children and have been suspected to be associated with each other., Aim: To examine the association between asthma or the use of asthma drugs and the prevalence of MIH., Design: In a population-based cross-sectional study, we recorded MIH in 9-year-old children in Aalborg Municipality, Denmark, born in the year 2000. We used a unique 10-digit civil personal number to link data on MIH to population-based medical register data. The exposure was inhaled asthma medication from birth date until date of dental examination. The outcome was the overall prevalence of MIH according to use of asthma medication. Odds ratios (OR) of having MIH were adjusted for gender, use of antibiotics and amoxicillin, maternal smoking, pre- and perinatal complication, and hospital admissions., Results: We examined 1837 children, of which 542 (29.5%) had one or more molar(s) with MIH. The adjusted odds ratio of having MIH was 0.95 (95% CI: 0.60-1.51) among children with prescriptions of inhaled asthma medication., Conclusion: In this study, where the results have been adjusted for confounding, we found no association between use of inhaled asthma medication and the prevalence of MIH., (© 2020 The Authors. International Journal of Paediatric Dentistry published by BSPD, IAPD and John Wiley & Sons Ltd.)