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Purpose: Whether breast density mediates associations between early life body size and pubertal timing with postmenopausal breast cancer is underexplored., Methods: We studied 33,939 Danish women attending the Capital Mammography Screening Program at ages 50-69 years. Early life anthropometry and pubertal timing information came from the Copenhagen School Health Records Register. Postmenopausal breast cancer information came from the Danish Breast Cancer Group database (n = 833). Breast density (BI-RADS) was categorized as low (n = 25,464; 75 %) or high. Risk ratios (RR) and hazard ratios (HR) were estimated using generalized linear regression and Cox proportional hazards analyses. Counterfactual mediation analyses were conducted., Results: Evidence was limited for associations between birthweight and pubertal timing with breast density or breast cancer. Childhood BMI was inversely associated with high breast density (age 13y, RR=0.77 [0.72-0.81] for a z-score of 0.6 versus 0) and breast cancer (HR=0.90 [0.83-0.96] per z-score). Breast density mediated 37 % (17-170 %) of this association. Although childhood height was associated with breast density and breast cancer, there were few indications of mediation by breast density., Conclusions: Breast density may partially explain the inverse association between childhood BMI and postmenopausal breast cancer, but not the positive association between childhood height and postmenopausal breast cancer., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Jennifer Lyn Baker reports a relationship with Novo Nordisk that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim/background: Patient-reported outcome measurement instruments are important tools in understanding a breast reconstruction's impact on the patients' quality of life. A psychometric validation is essential before applying a patient-reported outcome measurement instrument in clinical practice and research. The BREAST-Q is a specific, validated questionnaire for breast surgery outcomes that has been translated from English to Danish. It consists of 167 items in 7 pre-operative scales and 15 post-operative scales. This validation study aims to validate the Danish BREAST-Q reconstruction module., Material and Methods: Eligible women were included from January 2019 to June 2020. Multiple-item scales with summated scores and more than 40 complete responses were eligible for psychometric validation, and psychometric analyses examined reliability and validity using Rasch Analyses and Classical Test Theory. Measurements included test for local response dependence, item fit, differential item functioning, and more. Clinical validity was assessed using known-groups hypotheses., Results: We obtained 115 and 201 complete responses pre-and postoperatively, respectively. We validated 120 items in four preoperative and nine postoperative scales. The Rasch analyses disclosed evidence of local response dependence in eight scales. Chronbach's α ranged 0.81-0.95 after adjustment. Item fit was evaluated using item-restscore correlations and showed good fit in 98 % of items. Differential Item Functioning was found in four items but had very little effect on the model. Clinical validity was supported by the know-group analyses., Discussion/conclusion: The Danish BREAST-Q reconstruction module has good acceptability, feasibility and validity, and adequate reliability. The results support the use in a Danish population., Competing Interests: Conflict of interests The authors have no conflict of interests., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: A high body mass index (BMI, kg/m 2 ) is associated with decreased risk of breast cancer before menopause, but increased risk after menopause. Exactly when this reversal occurs in relation to menopause is unclear. Locating that change point could provide insight into the role of adiposity in breast cancer etiology., Methods: We examined the association between BMI and breast cancer risk in the Premenopausal Breast Cancer Collaborative Group, from age 45 up to breast cancer diagnosis, loss to follow-up, death, or age 55, whichever came first. Analyses included 609,880 women in 16 prospective studies, including 9956 who developed breast cancer before age 55. We fitted three BMI hazard ratio (HR) models over age-time: constant, linear, or nonlinear (via splines), applying piecewise exponential additive mixed models, with age as the primary time scale. We divided person-time into four strata: premenopause; postmenopause due to natural menopause; postmenopause because of interventional loss of ovarian function (bilateral oophorectomy (BO) or chemotherapy); postmenopause due to hysterectomy without BO. Sensitivity analyses included stratifying by BMI in young adulthood, or excluding women using menopausal hormone therapy., Results: The constant BMI HR model provided the best fit for all four menopausal status groups. Under this model, the estimated association between a five-unit increment in BMI and breast cancer risk was HR=0.87 (95% CI: 0.85, 0.89) before menopause, HR=1.00 (95% CI: 0.96, 1.04) after natural menopause, HR=0.99 (95% CI: 0.93, 1.05) after interventional loss of ovarian function, and HR=0.88 (95% CI: 0.76, 1.02) after hysterectomy without BO., Conclusion: The BMI breast cancer HRs remained less than or near one during the 45-55 year age range indicating that the transition to a positive association between BMI and risk occurs after age 55., Competing Interests: Declaration of Competing Interest none., (Published by Elsevier Ltd.)

Background: Associations between a high body mass index (BMI) at single timepoints during child- and adulthood and risks of post-menopausal breast cancer are well-established, but associations with BMI across the lifecourse remains largely unknown. Therefore, we examined whether lifecourse BMI trajectories were associated with risks of post-menopausal breast cancer overall and by estrogen receptor (ER) status., Methods: We included 6698 Danish women born 1930-1946. Information on BMI at ages 6-15 years came from the Copenhagen School Health Records Register, and information on BMI at ages 20, 30, 40, 50 and/or 50-64 years came from the Diet, Cancer and Health cohort. Breast cancer cases (n = 577) were identified in the Danish Breast Cancer Cooperative Group database. Six BMI trajectories were identified using latent class trajectory modelling. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression models., Results: Compared to women with a trajectory characterized by an average BMI gain across life, women with the two trajectories with steep increases in BMI during childhood and adolescence that thereafter largely stabilized, had lower risks of post-menopausal breast cancer and ER-positive tumors. The adjusted HRs for ER-positive tumors were 0.67 (95% CI: 0.47-0.95) and 0.68 (95% CI: 0.46-1.01), respectively. In contrast, women with a trajectory with a low gain in BMI during childhood and adolescence followed by a subsequent steep increase during adulthood, had higher risks of post-menopausal breast cancer and ER-positive tumors when compared to women with an average BMI gain. The adjusted HR for ER-positive tumors was 1.28 (95% CI: 0.98-1.67)., Conclusions: Our findings suggest that the timing of excess gain in BMI across the lifecourse impacts subsequent post-menopausal breast cancer risks. Thus, the BMI development across life is likely useful in the identification of women at increased risks of post-menopausal breast cancer., Competing Interests: Declaration of Competing Interest The authors report no conflict of interests., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Since the first version of the dietary inflammatory index (DII®) developed in the past decade, several other versions have been developed. However, to date no study has attempted to compare these versions with respect to their associations with biomarkers of inflammation., Objective: We aimed to investigate the relationship between four dietary inflammatory scores [DII, two energy-adjusted derivatives (E-DII and E-DII r ), and the Inflammatory Score of the Diet (ISD)], and circulating levels of several inflammatory markers and adipokines., Methods: This study included 17 637 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort with at least one marker of inflammation measured in blood. Associations between the four scores and C-reactive protein (CRP), interleukin (IL)6, IL10, IL1RA, tumor necrosis factor-α (TNFα), soluble tumor necrosis factor receptor-1 (sTNFR1), sTNFR2, leptin, soluble leptin receptor (sLeptin R), adiponectin, and High Molecular Weight (HMW) adiponectin were evaluated using multivariable linear regressions adjusted for potential confounders., Results: Positive associations were observed between the four dietary inflammatory scores and levels of CRP, IL6, sTNFR1, sTNFR2 and leptin. However, only the DII and the ISD were positively associated with IL1RA levels and only the DII and the E-DII r were positively associated with TNFα levels. The proportion of variance of each biomarker explained by the scores was lower than 2%, which was equivalent to the variance explained by smoking status but much lower than that explained by body mass index., Conclusions: Our results suggest that the four dietary inflammatory scores were associated with some biomarkers of inflammation and could be used to assess the inflammatory potential of diet in European adults but are not sufficient to capture the inflammatory status of an individual. These findings can help to better understand the inflammatory potential of diet, but they need to be replicated in studies with repeated dietary measurements., Competing Interests: Conflicts of Interest Dr. James R. Hébert owns controlling interest in Connecting Health Innovations LLC (CHI), a company that has licensed the right to his invention of the dietary inflammatory index (DII®) from the University of South Carolina in order to develop computer and smartphone applications for patient counseling and dietary intervention in clinical settings. Dr. Nitin Shivappa is an employee of CHI. The subject matter of this paper will not have any direct bearing on that work, nor has CHI-related activity exerted any influence on this project., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)

Background: This nationwide, register-based case-control study investigated the association between hysterectomy and risk of epithelial ovarian cancer according to histology and by history of endometriosis and menopausal hormone therapy (MHT) use., Methods: From the Danish Cancer Registry, all women registered with epithelial ovarian cancer at age 40-79 years during 1998-2016 were identified (n = 6738). Each case was sex- and age-matched to 15 population controls using risk-set sampling. Information on previous hysterectomy on benign indication and potential confounders was retrieved from nationwide registers. Conditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for the association between hysterectomy and ovarian cancer according to histology, endometriosis, and use of MHT., Results: Hysterectomy was not associated with risk of epithelial ovarian cancer overall (OR=0.99; 95% CI 0.91 -1.09) but was associated with reduced risk of clear cell ovarian cancer (OR=0.46; 95% CI 0.28-0.78). In stratified analyses, decreased ORs associated with hysterectomy were seen in women with endometriosis (OR=0.74; 95% CI 0.50-1.10) and in non-users of MHT (OR=0.87; 95% CI 0.76-1.01). In contrast, among long-term MHT users, hysterectomy was associated with increased odds for ovarian cancer (OR=1.20; 95% CI 1.03-1.39)., Conclusion: Hysterectomy was not associated with epithelial ovarian cancer overall but with reduced risk of clear cell ovarian cancer. Our findings may suggest a reduced risk of ovarian cancer after hysterectomy in women with endometriosis and in MHT non-users. Interestingly our data pointed to an increased ovarian cancer risk associated with hysterectomy among long-term users of MHT., Competing Interests: Declaration of Competing Interest Lene Mellemkjær has an immediate family member employed at Novo Nordisk, and has an immediate family member who owns stocks in Novo Nordisk. All other authors declare no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: Previous studies have established associations between body mass index and breast cancer, but fat mass is a more direct measure of the amount of fat tissue in the body than body mass index. This study examined the association between body fat mass, fat-free mass, and other anthropometric measures and breast cancer in postmenopausal women according to use of hormone replacement therapy (HRT)., Methods: From the Danish Diet, Cancer and Health cohort established during 1993-1997, 24,219 postmenopausal women were included who had anthropometric and bioimpedance measurements performed by a laboratory technician at baseline. Information on breast cancer incidence (outcome), other cancer diagnoses, and vital status (censoring variables) through 2016 was obtained from nationwide registers. Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CIs) while adjusting for known breast cancer risk factors and stratifying by HRT use and running age., Results: During a total of 431,104 person-years, 1919 women developed breast cancer. Among never-users of HRT, the HR for breast cancer at or after age 65 years was 1.06 (95% CI, 1.03-1.08) per 1 kg/m 2 higher body fat mass index (BFMI), and 1.30 (95% CI, 1.14-1.47) per 10% higher body fat percentage. The corresponding HRs for breast cancer before age 65 years were close to unity. The HRs were 1.11 (95% CI, 1.02-1.21) and 1.17 (95% CI, 1.10-1.23) for each 1 kg/m 2 increase in fat-free mass index, respectively, for breast cancer below and above age 65 years. Mutual adjustment attenuated the HRs for BFMI and body fat percentage, whereas the HRs for fat-free mass index were largely unaffected. Among ever-users of HRT, there was no statistical significant association between any of the body composition measures and breast cancer incidence in the two age groups., Conclusions: Among postmenopausal women who never used HRT, BFMI was associated with breast cancer in women aged 65 years or older. Fat-free mass index was found to be more strongly associated with postmenopausal breast cancer incidence than BFMI independently of age in never-users of HRT., Competing Interests: Conflicts of interest statement Lene Mellemkjær has an immediate family member employed at Novo Nordisk, and has an immediate family member who owns stocks in Novo Nordisk. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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.)

Objective: To examined the impact of reproductive factors on the relationship between radiation treatment (RT) for a first breast cancer and risk of contralateral breast cancer (CBC)., Methods: The Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study is a multi-center, population-based case-control study where cases are women with asynchronous CBC (N = 1521) and controls are women with unilateral breast cancer (N = 2211). Rate ratios (RR) and 95% confidence intervals (CI) were estimated using conditional logistic regression to assess the independent and joint effects of RT (ever/never and location-specific stray radiation dose to the contralateral breast [0, >0-<1Gy, ≥1Gy]) and reproductive factors (e.g., parity)., Results: Nulliparous women treated with RT (≥1Gy dose) were at increased risk of CBC compared with nulliparous women not treated with RT, although this relationship did not reach statistical significance (RR = 1.34, 95% CI 0.87, 2.07). Women treated with RT who had an interval pregnancy (i.e., pregnancy after first diagnosis and before second diagnosis [in cases]/reference date [in controls]) had an increased risk of CBC compared with those who had an interval pregnancy with no RT (RR = 4.60, 95% CI 1.16, 18.28). This was most apparent for women with higher radiation doses to the contralateral breast., Conclusion: Among young female survivors of breast cancer, we found some evidence suggesting that having an interval pregnancy could increase a woman's risk of CBC following RT for a first breast cancer. While sampling variability precludes strong interpretations, these findings suggest a role for pregnancy and hormonal factors in radiation-associated CBC., Competing Interests: Declaration of competing interest PC: Research Funding: 10X Genomics (institution), Illumina (institution), Canon (institution), Cellink (institution), Other: Amgen (stockholder). No other authors have conflicts to report., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Tamoxifen reduces the risk of contralateral breast cancer (CBC), but little is known about the long-term risk., Methods: From the database under the Danish Breast Cancer Cooperative Group (DBCG), we identified 15,863 users and 21,670 nonusers of tamoxifen among women diagnosed with breast cancer during 1977 to 2007. Information on CBC was obtained from the Danish Cancer Registry and the Danish Breast Cancer Cooperative Group database. Cox regression analyses were carried out with estimation of hazard ratios (HRs) of CBC. We also estimated the HRs of current and past use of tamoxifen., Results: Current use of tamoxifen was associated with reduced HRs of CBC independently of menopausal status and calendar-period. The HRs associated with past use of tamoxifen, however, varied among postmenopausal users from 1.50 (95% confidence interval [CI], 1.20-1.87) among users in 1977 to 1989 to 0.87 (95% CI, 0.70-1.06) and 1.05 (95% CI, 0.68-1.63) among users in 1990 to 1998 and 1999 to 2007, respectively. No excesses or deficits of CBC were found 10 or more years since the last use in postmenopausal women in any calendar-period., Conclusions: Our study confirms that tamoxifen protects against CBC while being treated. The effect of tamoxifen after cessation of treatment was not clear because of the inconsistency in results by calendar-period., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Recent evidence suggests that chronic lymphocytic leukemia (CLL) might occur following a response to an infectious agent. We conducted a population-based study including 4249 CLL patients diagnosed in Denmark from 1977 to 1997 and 15 690 frequency-matched controls to quantify risk of CLL following various airway infections. Through data linkage we gathered information on hospital inpatient/outpatient discharges that listed infections present at least 1 year prior to CLL. Using logistic regression, we calculated odds ratios (ORs) and 95% confidence intervals (CIs). Personal history of pneumonia was associated with significantly increased CLL risk (OR = 1.4; 1.2-1.8); risk was restricted to 1 to 4.99 years prior to CLL diagnosis (OR = 1.6; 1.2-2.0). Individuals with 3 or more prior pneumonia events had a significant 2.5-fold (1.1-5.6) elevated CLL risk, and risk increased with the number of pneumonia episodes (P(trend) < .001). None of 9 other respiratory-tract infections was significantly associated with CLL risk. Pneumonia might be a potential CLL trigger or it could represent premalignant immune disruption preceding CLL.

A population-based case-control study was conducted to evaluate risk of developing chronic lymphocytic leukemia (CLL) associated with personal and/or family history of autoimmune and related diseases. Data were obtained for all (n = 7764) patients diagnosed with CLL in Sweden and Denmark over a 40-year period and with linkable relatives, 16,658 matched control subjects, and first-degree relatives of patients (n = 17,991) and control subjects (n = 39,388). Odds ratios (ORs) were calculated to quantify risk of CLL in relation to personal/family history of 32 autoimmune and related disorders. The risk of CLL was significantly increased among subjects with a personal history of pernicious anemia (OR = 1.94; 1.18-3.18), mainly in the 0- to 1-year latency period. A significantly decreased risk of CLL was found among individuals with a personal history of chronic rheumatic heart disease (OR = 0.55; 0.33-0.93), particularly persons with a long latency (10+ years) between the 2 conditions. We found no association between personal or familial occurrence of other autoimmune or related disorders and CLL. If our results are confirmed, mechanistic studies examining how pernicious anemia might promote increased occurrence of CLL and how chronic rheumatic heart disease protects against CLL, perhaps related to long-term antibiotics use, may provide insights to the as-yet-unknown etiology of CLL.

Objective: We examined overall and cause-specific mortality in a population-based cohort of individuals prescribed paracetamol. We evaluated rates of death due to liver and renal disease, cancer, and other major causes of death., Method: Using the population-based pharmacoepidemiology prescription database of North Jutland County, Denmark, we identified nearly 50,000 persons receiving prescriptions for paracetamol from 1989 to 1995 and evaluated mortality through 1996. Standardized mortality ratios (SMRs) for 18 specific causes of death were computed for persons prescribed paracetamol compared with persons among the general population of the county., Results: SMRs were elevated regardless of cause of death, with a nearly doubled overall death rate among persons prescribed paracetamol. The mortality ratios were highest within 1 year of paracetamol prescription and tended to decline with increasing follow-up, especially for cancers. The magnitudes of the excess mortality risks for liver and renal diseases were not materially higher than for other causes of death., Conclusion: Paracetamol is a first-line analgesic for patients with a wide variety of chronic or serious illnesses and therefore is associated with increased rates of nearly all causes of death. The findings are an example of confounding by indication. Paracetamol may be a drug most prone to this form of bias in pharmacoepidemiologic studies. Future observational studies reporting adverse effects of paracetamol must thoroughly evaluate confounding by indication before making causal inferences.

Background: Dermatomyositis and polymyositis are associated with cancer, but previous nationwide studies have not had sufficient cases to test the association between myositis and specific cancer types. Our aim was to investigate the risk of specific cancer types in individuals with dermatomyositis and polymyositis., Methods: We did a pooled analysis of published national data from Sweden, Denmark, and Finland. All patients with dermatomyositis and polymyositis (> or =15 years old) were identified by discharge diagnosis from the Swedish National Board of Health (1964-83), Danish Hospital Discharge Registry (1977-89), and Finnish National Board of Health (1969-85). Personal details were matched to national cancer registries, to identify all cases of cancer up to 1987 in Sweden, 1995 in Denmark, and 1997 in Finland, and to national death registries for the same periods. We calculated standardised incidence ratios (SIR) for individual cancer sites for dermatomyositis and polymyositis separately, using national cancer rates by country, sex, age, and date., Findings: We identified 618 cases of dermatomyositis, of whom 198 had cancer. 115 of the 198 developed cancer after diagnosis of dermatomyositis. This disease was strongly associated with malignant disease (SIR 3.0, 95% CI 2.5-3.6), particularly ovarian (10.5, 6.1-18.1), lung (5.9, 3.7-9.2), pancreatic (3.8, 1.6-9.0), stomach (3.5, 1.7-7.3), and colorectal (2.5, 1.4-4.4) cancers, and non-Hodgkin lymphoma (3.6, 1.2-11.1). 137 of the 914 cases of polymyositis had cancer, which developed after diagnosis of polymyositis in 95. Polymyositis was associated with a raised risk of non-Hodgkin lymphoma (3.7, 1.7-8.2), and lung (2.8, 1.8-4.4) and bladder cancers (2.4, 1.3-4.7). In both dermatomyositis and polymyositis, risk of malignant disease was highest at time of myositis diagnosis., Interpretation: Our results provide evidence that dermatomyositis is strongly associated with a wide range of cancers. The overall risk of malignant disease is also modestly increased among patients with polymyositis, with an excess for some cancers.

Objective: It was our aim to evaluate the hypothesis that molar pregnancy is a marker of increased risk for cancer., Study Design: This was a nationwide cohort study of 1520 women, identified from the Danish National Register of Patients, in whom a molar pregnancy was diagnosed during the period 1977-1992 and of 1295 male partners of these women, traced in the Danish Central Population Register., Results: Linkage of the female roster with the Danish Cancer Registry through 1994 revealed 19 cases of gestational choriocarcinoma, whereas 0.04 was expected from the rates for the general population. Twenty cases of cancers of other types were observed with 24.9 expected (standardized incidence ratio, 0.8; 95% confidence interval, 0.5-1.2), but no specific type of cancer other than gestational choriocarcinoma occurred at a rate significantly different from that expected. Among the 1295 male partners notified in the Central Population Register, a total of 22 cancers were observed with 21.9 expected (standardized incidence ratio, 1.0; 95% confidence interval, 0.7-1.5)., Conclusion: Molar pregnancy is not associated with an increased risk for cancer other than gestational carcinoma.

Low or declining levels of serum cholesterol have been associated with increased mortality from cancer. We conducted a population-based cohort study of 1882 patients from one Danish county who received lipid-lowering drugs between January 1, 1991 and December 31, 1994. During the follow-up period of up to 4 years, 41 cancers were observed among users of lipid-lowering drugs, with 42.9 expected, to yield an age- and sex-standardized incidence ratio of 1.0 (95% confidence interval, 0.7-1.3). Although limited by small numbers and short follow-up period, examination by site of cancer and type of drug provided no evidence of an association. Further research is needed, however, with longer follow-up to assess more fully any potential cancer risk with these medications.