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Information on the contamination of Danish cereals and cereal products with Fusarium toxins is limited and the last survey is from 1984/1985. In the present study, the occurrence of deoxynivalenol (DON), nivalenol (NIV), HT-2 toxin, T-2 toxin and zearalenone (ZON) was investigated in flour of common wheat, durum wheat and rye. The samples were collected from 1998 to 2001 from both mills and the retail market in Denmark. A total of 190 flour samples were analysed for DON and NIV and about 60 samples for HT-2, T-2 toxin and ZON. DON was most frequently detected with an incidence rate of 78% over all samples for all years. The contamination level varied considerably from year to year, and for wheat and rye the highest incidence and DON concentrations were found in samples from the 1998 harvest. There were regular and heavy rainfalls in Denmark during the flowering period of the crops that year, and DON was found in all samples, with mean concentrations in wheat and rye flour of 191 μg kg[SUP-1] (n = 14) and 99 μg kg[SUP-1] (n = 16), respectively. Comparison of data from each harvest year showed higher contents of DON in samples of wheat (range 20-527 μg kg[SUP-1]) than in rye (20-257 μg kg[SUP-1]). Contents of NIV, HT-2 toxin and ZON in samples of wheat and rye were generally low, and even in positive samples the contents were close to the detection limit of the methods. The T-2 toxin was detected in only a few of the wheat samples and in low amounts. However, the toxin was found in about 50% of the rye samples collected during 1998-2000, with a mean content of 49 μg kg[SUP-1] (n = 25). Durum wheat flour showed the highest DON contamination level, and all samples (n = 33) collected during 2000 and 2001 contained DON with means and medians above 1100 μg kg[SUP-1]. Over 70% of the samples contained more than 500 μg kg[SUP-1] DON, and the highest observed concentration was 2591 μg kg[SUP-1]. The concentration of T-2 toxin in durum wheat flour... [ABSTRACT FROM AUTHOR]

Background and purpose: Capecitabine can be used as first-line treatment for advanced breast cancer. However, real-world data on efficacy of capecitabine in this setting is sparse. The purpose of the study is to evaluate outcomes of patients with Human Epidermal Growth Factor Receptor (HER2)-normal advanced breast cancer treated with capecitabine monotherapy as first-line treatment., Material and Methods: The study utilized the Danish Breast Cancer Group (DBCG) database and was conducted retrospectively across all Danish oncology departments. Inclusion criteria were female patients, with HER2-normal advanced breast cancer treated with capecitabine monotherapy as the first-line treatment from 2010 to 2020. The primary endpoints were overall survival (OS) and progression-free survival (PFS)., Results: A total of 494 patients were included. Median OS was 16.4 months (95% confidence interval [CI]: 14.5-18.0), and median PFS was 6.0 months (95% CI: 5.3-6.7). Patients with estrogen receptor (ER)-positive disease had significantly longer OS (median: 22.8 vs. 10.5 months, p < 0.001) and PFS (median: 7.4 vs. 4.9 months, p = 0.003), when compared to ER-negative patients. Stratifying by age, patients under 45 years displayed a median PFS of 4.1 months, while those aged 45-70 years and over 70 years had median PFS of 5.7 and 7.2 months, respectively (p = 0.01)., Interpretation:  In this nationwide study, the efficacy of capecitabine as a first-line treatment for HER2-normal advanced breast cancer is consistent with other, mainly retrospective, studies. However, when assessed against contemporary and newer treatments, its effectiveness appears inferior to alternative chemotherapies or targeted therapies.

Background: Primary metastatic breast cancer (pMBC) accounts for 5-10% of annual breast cancers with a median survival of 3-4 years, varying among subtypes. In Denmark, the incidence of breast cancer increased until 2010, followed by a stabilisation. Several factors influencing pMBC incidence and survival, including screening prevalence, staging methods, and classification standards, remain pivotal but inadequately documented., Material and Method: This retrospective observational study involving pMBC patients diagnosed between 2000 and 2020 encompassed all Danish oncology departments. Data from the Danish Breast Cancer Group database and the National Patient Register included diagnosis specifics, demographics, treatment, and follow-up., Results: Between 2000 and 2020, 3,272 patients were diagnosed with pMBC, a rise from 355 patients in 2000-2004 to 1,323 patients in 2015-2020. The increase was particularly observed in patients aged 70 years or older. Changes in tumour subtypes were observed, notably with a rise in human epidermal growth factor receptor 2 (HER2)-positive cases but a steady distribution of estrogen receptor (ER) status. Diagnostic practices changed over the two decades, with 6% evaluated with PET/CT (positron emission tomography-computed tomography) or CT (computed tomography) with a bone evaluation in 2000-2004 and 65% in 2015-2020. Overall survival (OS) improved from 23 months in 2000-2004 to 33 months in 2015-2020. In patients with ER-positive and HER2-positive disease, the multivariable model showed improved survival by year of diagnosis, and further, patients with ER-negative/HER2-negative disease fared worse the first 2 years after diagnosis., Interpretation: Our study delineates changes in the treatment and survival of pMBC over two decades. Stage migration, screening introduction, and changes in registration practice, however, prevent a valid assessment of a possible causal relationship.

Background: Breast cancer incidence is now the highest among all cancers and accountable for 6.6% of all cancer-related deaths worldwide. Studies of the prognostic utility of plasma C-reactive protein (CRP) measurement in early-stage breast cancer have given discrepant results., Methods: We identified 6,942 patients in the Danish Breast Cancer Cooperative Group database with early-stage breast cancer diagnosed between 2002 and 2016 who had a measure of pretreatment plasma CRP. Outcomes were recurrence-free interval and survival for a period up to 10 years. We analyzed associations with plasma CRP using Fine-Gray proportional subdistribution hazards model with recurrence-free interval. Data on plasma CRP were analyzed per doubling of concentration and in relation to CRP levels of <3 mg/L, 3 to 10 mg/L, and >10 mg/L and stratified according to standard clinical parameters in sensitivity analyses., Results: A doubling of the plasma CRP concentration was associated with increased risk of recurrence (multivariate adjusted HR, 1.05; 95% CI, 1.01-1.08) and shorter survival (HR, 1.13; 95% CI, 1.09-1.16) in multivariate analyses. Survival was shorter in patients with plasma CRP levels of 3 to 10 and >10 mg/L versus <3 mg/L, with multivariate adjusted HRs of 1.30; 95% CI, 1.17-1.45 and 1.65; 95% CI, 1.39-1.95, respectively., Conclusions: Elevated plasma CRP measured before treatment in patients with early-stage breast cancer is an independent biomarker of increased risk of recurrence and early death., Impact: CRP measures before treatment might be used to individualize follow-up of patients with early-stage breast cancer., (©2024 American Association for Cancer Research.)

Background: Considering the recent advancements in the treatment of breast cancer with low expression of human epidermal growth factor receptor 2 (HER2), we aimed to examine inter-laboratory variability in the assessment of HER2-low breast cancer across all Danish pathology departments., Methods: From the Danish Breast Cancer Group, we obtained data on all women diagnosed with primary invasive breast cancer in 2007-2019 who were subsequently assigned for curatively intended treatment., Results: Of 50,714 patients, HER2 score and status were recorded for 48,382, among whom 59.2% belonged to the HER2-low group (score 1+ or 2+ without gene amplification), 26.8% had a HER2 score of 0, and 14.0% were HER2 positive. The proportion of HER2-low cases ranged from 46.3 to 71.8% among pathology departments (P < 0.0001) and from 49.3 to 65.6% over the years (P < 0.0001). In comparison, HER2 positivity rates ranged from 11.8 to 17.2% among departments (P < 0.0001) and from 12.6 to 15.7% over the years (P = 0.005). In the eight departments with the highest number of patients, variability in HER2-low cases increased from 2011 to 2019, although the same immunohistochemical assay was used. By multivariable logistic regression, the examining department was significantly related to both HER2 score 0 and HER2 positivity (P < 0.0001) but showed greater dispersion in odds ratios in the former case (range 0.25-1.41 vs. 0.84-1.27)., Conclusions: Our data showed high inter-laboratory variability in the assessment of HER2-low breast cancer. The findings cast doubt on whether the current test method for HER2 is robust and reliable enough to select HER2-low patients for HER2-targeted treatment in daily clinical practice., (© 2023. The Author(s).)

Introduction: The Danish Medicines Council recommends that patients with estrogen receptor and human epidermal growth factor receptor 2-negative, programmed death-ligand 1 (PD-L1)-positive advanced breast cancer receive atezolizumab in combination with nab-paclitaxel. The approval was largely based on results from Impassion130 that showed a beneficial progression-free survival (PFS) and overall survival (OS) in PD-L1-positive patients who received atezolizumab and nab-paclitaxel., Methods: We conducted a retrospective, population-based study that included patients who received atezolizumab for advanced breast cancer from October 2019 to September 2022. The primary endpoints were PFS and OS., Results: This study included 74 advanced breast cancer patients. Their median age was 54.5 years, and 21 (28.4%) of the patients had de novo advanced disease. Most patients received first-line treatment with atezolizumab (83.8%). The median PFS was 6.0 months (95% confidence interval (CI): 4.7-8.4 months) and the median OS was 14.3 months (95% CI: 9.9-22.2 months). A total of 48 patients received atezolizumab and nab-paclitaxel in accordance with guidelines from the Danish Medicines Council., Conclusions: This real-world study expectedly showed numerically lower survival outcomes than the phase III trial Impassion130, but met the standards of efficacy set by real-world studies in other countries. A need exists for increased attention to the criteria for receiving atezolizumab., Funding: none., Trial Registration: The study was approved by the Oncological Committee of the DBCG, the Research Overview of the Capital (P-2022-828) and the Centre for Health of the Capital Region (R-22060674)., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

Background: The purpose was to investigate the treatment flow of patients with HER2-positive metastatic breast cancer (mBC), progression-free survival (PFS) and overall survival (OS) across treatment lines and adherence to guidelines (defined as trastuzumab, pertuzumab and chemotherapy first line, where 85% received vinorelbine as backbone and T-DM1 second line). Furthermore, we identified clinical markers to predict the risk of developing brain metastases., Material and Methods: Patients with HER2-positive mBC, diagnosed between 01.01.2014-31.12.2019, registered in the database of the Danish Breast Cancer Group were included in this real-word study. Clinical follow-up was assessed until 01.10.2020 and complete follow-up for overall survival until 01.10.2021. Survival data were analyzed using the Kaplan-Meier method with guidelines adherence analyzed as a time-varying covariate, and the risk of CNS metastasis was estimated by the cumulative incidence function., Results: 631 patients were included. 329 (52%) patients followed the guidelines. The median OS for all patients was 42.3 months (95% Cl, 38.2-48.4), and significantly higher for the patients who followed guidelines; NA (95% CI, 78.2-NA). The median PFS for all patients was 13.4 months (95% Cl, 12.1-14.8), 6.6 (95% Cl, 5.8-7.6) and 5.8 (95% Cl, 4.9-6.9) for first, second and third line of treatment, respectively. Patients with ER-negative mBC had a higher risk of developing brain metastases and patients with high tumor burden had a higher risk of developing brain metastases with an adjusted HR of 0.69 (95% CI, 0.49-0.98), p  = 0.047 and 2.69 (95% CI, 1.45-5.00), p  = 0.002, respectively., Conclusion: We found that only half of the patients with HER2-positive mBC, received first and second-line treatment according to national guidelines. Patients receiving treatment according to guidelines had a significantly higher median OS compared to patients who did not. We also found that patients with ER-negative disease or high tumor burden had a significantly higher risk of developing brain metastases.

Background: More than 4500 women are diagnosed with breast cancer each year in Denmark, however, despite adequate treatment 10-30% of patients will experience a recurrence. The Danish Breast Cancer Group (DBCG) stores information on breast cancer recurrence but to improve data completeness automated identification of patients with recurrence is needed., Methods: We included patient data from the DBCG, the National Pathology Database, and the National Patient Registry for patients with an invasive breast cancer diagnosis after 1999. In total, relevant features of 79,483 patients with a definitive surgery were extracted. A machine learning (ML) model was trained, using a simplistic encoding scheme of features, on a development sample covering 5333 patients with known recurrence and three times as many non-recurrent women. The model was validated in a validation sample consisting of 1006 patients with unknown recurrence status., Results: The ML model identified patients with recurrence with AUC-ROC of 0.93 (95% CI: 0.93-0.94) in the development, and an AUC-ROC of 0.86 (95% CI: 0.83-0.88) in the validation sample., Conclusion: An off-the-shelf ML model, trained using the simplistic encoding scheme, could identify recurrence patients across multiple national registries. This approach might potentially enable researchers and clinicians to better and faster identify patients with recurrence and reduce manual patient data interpretation.

Background: The recommended first-line treatment for advanced, ER+/HER2 negative breast cancer is a CDK 4/6 inhibitor in combination with an endocrine backbone. This study investigated the use of palbociclib, as first- or second-line therapy for advanced breast cancer patients in a real-world setting., Material and Methods: This retrospective, population-based study included all Danish, advanced breast cancer patients with ER+/HER2 negative disease who initiated first- or second-line treatment with palbociclib from January 1 st , 2017, until December 31 st , 2020. The primary outcomes were PFS and OS., Results: The study included 1054 advanced breast cancer patients with a mean age of 66.8 years. Median OS was 51.7 months (95% CI, 44.9-54.6) for all patients in the first-line setting ( n  = 728) and median PFS was 24.3 months (95% CI, 21.7-27.8). Patients treated in second line ( n  = 326) had a median OS of 32.5 months (95% CI, 29.9-35.9) and a median PFS of 13.6 months (95% CI, 11.5-15.7). In first-line setting, the PFS and OS were significantly different for endocrine sensitive patients treated with AI (aromatase inhibitor) ( n  = 423) vs. fulvestrant ( n  = 158) as endocrine backbone to palbociclib (median PFS AI 31.3 months vs fulvestrant 19.9 months, p  = 0.002 and median OS AI 56.9 months vs. fulvestrant 43.6 months, p  = 0.001). In endocrine resistant patients ( n  = 145), no statistically significant difference in PFS was shown (median PFS AI 21.5 months vs. fulvestrant 12.0 months, p  = 0.09), whereas OS was significantly different (median OS AI 43.5 months vs. fulvestrant 28.8 months, p  = 0.02)., Conclusion: In this real-world study, treatment with palbociclib combination therapy met the standards of efficacy set by the phase III trials, PALOMA-2 and PALOMA-3, and the standards set by real-world studies in other countries. The study showed significantly different outcomes in terms of PFS and OS in endocrine sensitive patients comparing AI vs. fulvestrant as endocrine backbone to palbociclib as first-line therapy.

Background: Dual blockade with trastuzumab and pertuzumab combined with neoadjuvant chemotherapy (NACT) has been increasingly used for HER2-positive tumours >2 cm and/or with positive axillary lymph nodes in order to evaluate pathologic response and obtain better surgical management. SB3 is a registered biosimilar trastuzumab approved following a phase III trial demonstrating similar efficacy in the neoadjuvant setting as trastuzumab. However, the study was done without pertuzumab., Method: The database of the Danish Breast Cancer Group was used to extract data on all patients who started NACT with SB3 and pertuzumab between September 1, 2018 and August 31, 2019. The primary endpoint was pathological complete response (pCR) rate., Results: In total 215 patients received NACT and dual blockade. The median age was 55 (24-81). NACT used was cyclophosphamide and epirubicin followed by weekly paclitaxel (62% on six cycles, 35% on eight cycles) or other chemotherapy followed by weekly paclitaxel (3%). Overall, 56% of patients achieved pCR. 60 of 88 node-positive patients pre-NACT achieved ypN0(i-) after neoadjuvant treatment. pCR rate was significantly associated with estrogen receptor status and malignancy grade. An association with CEP17/HER2-ratio was assessed., Conclusion: Real world data on dual blockade with SB3 and pertuzumab in combination with NACT in a nationwide population-based study show a pCR rate comparable to that seen in previous clinical studies., Competing Interests: Declaration of competing interest MBJ: Institutional grants from Nanostring Technologies and Oncology Venture, EHJ: Advisory board for Pfizer, Roche, Astra Zeneca and Novartis., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Randomized clinical trials do not include a population that truly reflects a real-world population, due to their inclusion and exclusion criteria. This leads to concerns about the applicability of these studies in a clinical practice. In the present study, we aim to describe the clinical and demographic characteristics, treatment patterns, and clinical outcomes in a population of patients with HER2-positive metastatic breast cancer who received pertuzumab and trastuzumab as first-line treatment in a real-world setting., Methods: The database of the Danish Breast Cancer Group was used to assemble data on patients included in the period April 2013 to August 2017. The primary endpoints were overall survival (OS) and progression-free survival (PFS)., Results: A cohort of 291 patients with a median age of 58 years was registered. Hereof 112 (38%) patients with de novo disease (primary disseminated) and 179 (62%) with recurrence. The median follow-up for OS was 24.1 months. The median OS was 41.8 months (95% CI, 37.7 to NE) and the median PFS was 15.8 months (95% CI, 14.0 to 19.9). For de novo patients alone, the median OS was not reached whereas the median PFS was 17.9 months (95% CI, 14.3 to 27.3). Hazard ratios for patients receiving vinorelbine showed comparable results as for the whole population., Conclusion: This heterogeneous patient population in a real-world setting had a PFS comparable with what could be expected from the related randomized trial. The de novo patients had better OS and PFS as compared to patients with recurrence., Competing Interests: Declaration of Competing Interest This study was funded by F. Hoffmann–La Roche and Genentech., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Ovarian cancer has the highest mortality rate among gynaecological cancers and is the tenth most frequent cancer among women. 80% of patients with advanced stage disease will experience a progression either during or after treatment., Methods: This was a retrospective, observational study of all women referred to adjuvant or neoadjuvant treatment for ovarian cancer between 1 June 2013 and 31 May 2014 at two university hospitals in Denmark., Results: We included 142 women diagnosed with ovarian cancer. The median overall survival from diagnosis was 48.5 months (95% confidence interval (CI): 36.6-57.9 months). Median survival after the first, second, third, fourth and fifth progression was 19.3 (95% CI: 13.9-27-3), 11.4 (95% CI: 7.7-18.8), 9.5 (95% CI: 6.3-12.7), 8.3 (95% CI: 7.6-11.5) and 5.6 
(95% CI: 2.9-not assessed) months, respectively. Median progression-free survival from diagnosis was 15.6 months (95% CI: 14.3-18.4 months). Median progression-free survival after first, second, third, fourth and fifth progression was 9.2 (95% CI: 7.7-10.6), 6.0 (95% CI: 3.5-7.7), 3.3 (95% CI: 2.6-4.6), 4.9 (95% CI: 3.6-8.3) and 3.0 (95% CI: 2.4-5.7) months, respectively. The most frequently used treatment at first progression was carboplatin and pegylated liposomal doxorubicin (n = 37). The most used non-platinum containing treatment at progression was pegylated liposomal doxorubicin (n = 26) followed by paclitaxel (n = 23)., Conclusions: Ovarian cancer remains a highly aggressive disease with most patients diagnosed in advanced stages. Treatment has not changed much in the past 15 years and the same is evident for the overall survival., Funding: Tobias Berg received an unrestricted research grant from the Danish Cancer Society., Trial Registration: not relevant., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

Background: Iron deficiency is a frequent side effect of blood donation. In recent years, several studies have described genetic variants associated with iron concentrations. However, the impact of these variants on iron levels is unknown in blood donors. Knowledge of genetic variants that predispose donors to iron deficiency would allow bleeding frequency and iron supplementation to be tailored to the individual donor., Study Design and Methods: The genotypes of five specific single-nucleotide polymorphisms (SNPs) in three genes that have been previously associated with iron status and/or restless leg syndrome (RLS) were investigated in two groups of female blood donors. The first group had low iron stores (serum ferritin ≤ 12 µg/L, n = 657), and the second group had normal to high iron stores (serum ferritin > 30 µg/L, n = 645). Genotype distribution for each of the SNPs was compared between the two groups., Results: Homozygosity for the T-allele of BTBD9 rs9296249 was associated with lower serum ferritin. The odds ratio for low serum ferritin was 1.35 (95% confidence interval, 1.02-1.77; p = 0.03) when comparing donors with the TT genotype with donors with the CT genotype., Conclusion: A frequent polymorphism in BTBD9 was significantly associated with serum ferritin. This polymorphism has previously been associated with RLS, but not low iron stores in blood donors., (© 2012 American Association of Blood Banks.)

The release of nickel, chromium and lead from electric kettles to water under conditions simulating regular household use was investigated. Ten out of 26 kettles sold on the Danish market released more than 50 micrograms/l nickel to water, whereas neither lead nor chromium was released in any significant amount. Fifty micrograms/l of nickel in water was chosen as the threshold of action, because concentrations below this value were considered unlikely to provide outbreaks of eczema for those consumers suffering from contact allergy to nickel, who are also sensitive to the content of nickel in the diet. This first part of the study was followed up by a dialogue between the kettle producers and the Danish authorities, leading to a change of construction or design for those kettles that did not comply with the criteria. As a follow-up study another ten kettles were studied to check whether compliance was improved. Two of these ten kettles still released more than 50 micrograms/l nickel to water under the test conditions. These two kettles, however, were subsequently withdrawn from the market. Coffee machines tested similarly did not release aluminium, lead, chromium or nickel in quantities of any significance.

Sera from 260 men from Denmark and elsewhere attending two Copenhagen sauna clubs for homosexual men during nine months of 1982-1983 were investigated for markers for syphilis, hepatitis A and B, and human immunodeficiency virus (HIV). Five per cent (12 men) had active syphilis, and another 35% (92) had a history of and/or serologic markers for syphilis. Ninety-four men (36%) were positive for antibodies to hepatitis A virus, ten (4%) were positive for hepatitis B surface antigen (HBsAg), and 153 (59%) were positive for antibodies to HBsAg. Antibodies to HIV were found in 45 (20%) of the 220 men investigated for this marker. Markers for hepatitis A and B and for syphilis were more frequent in the HIV antibody-positive individuals, but the association was significant only for markers for hepatitis B (relative risk = 2.0). Thus STD markers had little predictive value for seropositivity for antibodies to HIV. Among 37 men investigated more than once, a seroconversion rate of 3% per month for antibodies to HIV was found, but this estimate must be taken with reservation. The rate of seropositivity for antibodies to HIV among men from Denmark was 23%, and three (8%) of the 40 HIV-positive Danish men developed the acquired immunodeficiency syndrome (AIDS) during the four years following the initial investigation. This study shows that by 1982-1983 HIV had spread considerably in the Danish high-risk group, although there were only seven reported cases of AIDS in the country at that time.