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Abstract Neutrophil extracellular traps (NETs) have been implicated in the pathology of various inflammatory conditions. In cancer, NETs have been demonstrated to induce systemic inflammation, impair peripheral vessel and organ function and promote metastasis. Here we show that the plasma level of NETs is significantly higher in patients with metastatic breast cancer compared to those with local disease, or those that were considered cured at a 5‐year follow‐up, confirming NETs as interesting therapeutic targets in metastatic breast cancer. Administration of DNase I is one strategy to eliminate NETs but long‐term treatment requires repeated injections and species‐specific versions of the enzyme. To enhance administration and therapeutic efficacy, we have developed an adeno‐associated virus (AAV) vector system for delivery of murine DNase I and addressed its potential to counteract cancer‐associated pathology in the murine MMTV‐PyMT model for metastatic mammary carcinoma. The AAV vector is comprised of capsid KP1 and an expression cassette encoding hyperactive murine DNase I (AAV‐mDNase I) under the control of a liver‐specific promotor. This AAV‐mDNase I vector could support elevated expression and serum activity of murine DNase I over at least 8 months. Neutrophil Gelatinase‐Associated Lipocalin (NGAL), a biomarker for kidney hypoperfusion that is upregulated in urine from MMTV‐PyMT mice, was suppressed in mice receiving AAV‐mDNase I compared to an AAV‐null control group. Furthermore, the proportion of mice that developed lung metastasis was reduced in the AAV‐mDNase I group. Altogether, our data indicate that AAV‐mDNase I has the potential to reduce cancer‐associated impairment of renal function and development of metastasis. We conclude that AAV‐mDNase I could represent a promising therapeutic strategy in metastatic breast cancer.

Abstract Somatic copy number variations (CNVs), including abnormal chromosome numbers and structural changes leading to gain or loss of genetic material, play a crucial role in initiation and progression of cancer. CNVs are believed to cause gene dosage imbalances and modify cis-regulatory elements, leading to allelic expression imbalances in genes that influence cell division and thereby contribute to cancer development. However, the impact of CNVs on allelic gene expression in cancer remains unclear. Allele-specific expression (ASE) analysis, a potent method for investigating genome-wide allelic imbalance profiles in tumors, assesses the relative expression of two alleles using high-throughput sequencing data. However, many existing methods for gene-level ASE detection rely on only RNA sequencing data, which present challenges in interpreting the genetic mechanisms underlying ASE in cancer. To address this issue, we developed a robust framework that integrates allele-specific copy number calls into ASE calling algorithms by leveraging paired genome and transcriptome data from the same sample. This integration enhances the interpretability of the genetic mechanisms driving ASE, thereby facilitating the identification of driver events triggered by CNVs in cancer. In this study, we utilized BASE to conduct a comprehensive analysis of ASE in high hyperdiploid acute lymphoblastic leukemia (HeH ALL), a prevalent childhood malignancy characterized by gains of chromosomes X, 4, 6, 10, 14, 17, 18, and 21. Our analysis unveiled the comprehensive ASE landscape in HeH ALL. Through a multi-perspective examination of HeH ASEs, we offer a systematic understanding of how CNVs impact ASE in HeH, providing valuable insights to guide ASE studies in cancer.

Abstract Background Nutrition interventions targeting early childhood can be cost-effective and may provide lifelong, intergenerational benefits. From October 2022 to April 2023 the Nutrition Now (NN) e-learning resource was implemented within Early Childhood Education and Care centres and the Maternal and Child Healthcare Centre (MCHC) in a southern Norwegian municipality. As part of the NN project, the present study aims to explore the MCHC staff’s experiences with implementing the NN resource, to gain insights into measures important to scale up digital early-life nutrition interventions. Methods Three group interviews were conducted among public health nurses and midwives alongside one individual interview with the department leader of a MCHC in May 2023. An inductive thematic analysis, as described by Braun and Clarke, was conducted to generate the key themes and subthemes regarding the implementation process of NN within the MCHC. Results Three main themes were generated: [1] Important resource but not always utilized; [2] Parents are interested but had issues with access; and [3] Staff and stakeholder buy-in and commitment needed from the start. Overall, the staff viewed the NN resource as a potential tool for promoting diet-related topics and believed it could support the guidance they were already providing parents. However, few staff members fully familiarized themselves with the resource. While staff perceived parents as positive when informed about NN, they believed issues such as access challenges, competing platforms, and time constraints reduced parental engagement. Lastly, staff suggested improvements for NN’s implementation, including enhanced training, better planning, assigning champions, and lowering the threshold for access. Conclusion The findings of this study suggest that the real-world implementation of digital evidence-based health behaviour interventions is feasible but would be enhanced by employing strategies focusing on engagement and utilization. Trial registration The main study is registered in the ISRCTN registry with ID ISRCTN10694967, https://doi.org/10.1186/ISRCTN10694967 . (Registration date: 19-06-2022).

Abstract Background Physical function is an important risk factor for fracture. Previous studies found that different physical tests (e.g., one‐leg standing [OLS] and timed up and go [TUG]) predict fracture risk. This study aimed to determine which physical function test is the most optimal independent predictor of fracture risk, together with clinical risk factors (CRFs) used in fracture risk assessment (FRAX) and bone mineral density (BMD). Methods In total, 2321 women out of the included 3028 older women, aged 77.7 ± 1.6 (mean ± SD), in the Sahlgrenska University Hospital Prospective Evaluation of Risk of Bone Fractures study had complete data on all physical function tests and were included in the analysis. At baseline, hand grip strength, OLS, TUG, walking speed and chair stand tests were performed. All incident fractures were confirmed by X‐ray or review of medical records and subsequently categorized as major osteoporotic fractures (MOFs), hip fractures and any fracture. Multivariate Cox regression (hazard ratios [HRs] and 95% confidence intervals [CIs]) analyses were performed with adjustments for age, body mass index (BMI), FRAX CRFs, femoral neck BMD and all physical function tests as predictors both individually and simultaneously. Receiver operating characteristic (ROC) analyses and Fine and Gray analyses were also performed to investigate associations between physical function and incident fractures. Results OLS was the only physical function test to be significantly and independently associated with increased risk of any fracture (HR 1.13 [1.04–1.23]), MOF (HR 1.15 [1.04–1.26]) and hip fracture (HR 1.34 [1.11–1.62]). Adjusting for age, BMI, CRFs and femoral neck BMD did not materially alter these associations. ROC analysis for OLS, together with age, BMI, femoral neck BMD and CRFs, yielded area under the curve values of 0.642, 0.647 and 0.732 for any fracture, MOF and hip fracture, respectively. In analyses considering the competing risk of death, OLS was the only physical function test consistently associated with fracture outcomes (subhazard ratio [SHR] 1.10 [1.01–1.19] for any fracture, SHR 1.11 [1.00–1.22] for MOF and SHR 1.25 [1.03–1.50] for hip fracture). Walking speed was only independently associated with the risk of hip fracture in all Cox regression models and in the Fine and Gray analyses. Conclusions Among the five physical function tests, OLS was independently associated with all fracture outcomes, even after considering the competing risk of death, indicating that OLS is the most reliable physical function test for predicting fracture risk in older women.

Decentralized clinical trials have gained in popularity over the last years due to their advantages related to broadening recruitment strategies and resource saving possibilities. As more clinical trials adopt decentralized strategies, it is essential to share the knowledge about both successful and unsuccessful efforts in the research community. In the present commentary, we explore potential reasons that led to early termination of a decentralized clinical trial in Oncology.

Abstract Background Population-based cancer quality registries are of great importance for the improvement of cancer care. However, little is known about the quality of recurrence data in cancer quality registries. The aim of this study was to evaluate data quality in the regional Breast Cancer Quality Registry of Central Sweden, with emphasis on the validity of recorded information on recurrence. Methods Validation by re-abstraction was performed on a random sample of 800 women with primary invasive breast cancer stage I-III diagnosed between 1993 and 2010, of which 400 had at least one registered recurrence and 400 had no registered recurrence. Registry data were compared with data from medical records. Exact agreement, correlation and kappa values, sensitivity and specificity were calculated. Results Seven hundred forty-seven women (93%) were available for analysis. Exact agreement was high for diagnostics, tumor characteristics, surgery, and adjuvant oncological treatment (90% or more for most variables). The registry’s sensitivity was low for regional recurrence (47%), but higher for local and distant recurrence (80% and 75%), whereas specificity was overall high (≥ 95%). Combining all recurrence categories irrespective of localization improved sensitivity to 90% with a specificity of 91%. In 87% of women, the date of first recurrence according to medical records fell within ± 90 days of the date recorded in the registry. Conclusions While the quality of data in the regional Breast Cancer Quality Registry was generally high, data accuracy on recurrences was lower. The overall precision of identifying any recurrence, irrespective of localization, was high. However, the accuracy of classification of recurrences (local, regional or distant) was lower, with evidence of underreporting for each of the recurrence categories. Given the importance of recurrence-related outcomes in the assessment of quality of care, efforts should be made to improve the reporting of recurrences.

Abstract Genomic analyses have redefined the molecular subgrouping of pediatric acute lymphoblastic leukemia (ALL). Molecular subgroups guide risk-stratification and targeted therapies, but outcomes of recently identified subtypes are often unclear, owing to limited cases with comprehensive profiling and cross-protocol studies. We developed a machine learning tool (ALLIUM) for the molecular subclassification of ALL in retrospective cohorts as well as for up-front diagnostics. ALLIUM uses DNA methylation and gene expression data from 1131 Nordic ALL patients to predict 17 ALL subtypes with high accuracy. ALLIUM was used to revise and verify the molecular subtype of 281 B-cell precursor ALL (BCP-ALL) cases with previously undefined molecular phenotype, resulting in a single revised subtype for 81.5% of these cases. Our study shows the power of combining DNA methylation and gene expression data for resolving ALL subtypes and provides a comprehensive population-based retrospective cohort study of molecular subtype frequencies in the Nordic countries.

Summary: Background: Estrogen receptor-low (ER-low) HER2-negative breast cancer has similar pathological and molecular characteristics as triple-negative breast cancer (TNBC), and it is questionable whether it should be considered a separate entity. When the international guidelines lowered the cutoff for ER positivity to ≥1% in 2010, the ≥10% threshold was kept in Sweden. ER-low breast cancer (ER 1–9%) is thus in Sweden treated as TNBC. We aimed to describe patient and tumor characteristics, treatment patterns and overall survival in a Swedish population-based cohort of patients with ER-zero and ER-low HER2-negative breast cancer treated as TNBC. Methods: All TNBC cases diagnosed in Sweden 2008–2020 were included in a population-based cohort study. Patient, tumor and treatment characteristics were analyzed by ER-status (ER 0% vs 1–9%), and associations between subgroups compared using χ2 test. Survival endpoint was overall survival (OS), and Kaplan–Meier curves were estimated. Cox proportional hazards models were used to estimate adjusted hazard ratios comparing ER-low to ER-zero. Findings: Of the 5655 tumors, 90.1% had an ER expression of 0%, while 9.9% were ER-low. ER-low tumors were grade III in 69.4% (80.8% in ER-zero tumors, p-value = 0.001), with a median Ki67 of 60% (63% in ER-zero tumors, p-value = 0.005). There were no significant differences in given chemotherapy (p = 0.546). A pathological complete response (pCR) was achieved in 28.1% of ER-low tumors (25.1% in ER-zero tumors). In the unadjusted analysis of OS, women with ER-low disease had a borderline but not significantly better OS than those with ER-zero disease (HR 0.84 (95% CI 0.71–1.00), p = 0.052). ER-status 1–9% vs 0% was not associated with OS in the multivariable analysis (HR 1.11 (0.90–1.36)). Distant disease-free survival did not differ by ER-status 0% vs 1–9% (HR 0.97 for ER-zero vs ER-low (0.62–1.53), p = 0.905). After preoperative treatment, the impact of pCR for OS did not significantly differ between ER-zero or ER-low disease. Interpretation: ER-low HER2-negative breast cancer has characteristics and prognosis similar to TNBC, when treated in the same way. Therefore, it seems reasonable to use a ≥10% threshold for ER positivity. This would provide patients with ER-low tumors the same treatment opportunities as patients with TNBC, within studies and within clinical routine. Funding: This work was financially supported by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, in accordance with terms and conditions of a Master Collaboration Agreement between the company and Karolinska Institutet.

In boreal forests fires often ignite and spread within the dominant moss and lichen cover of the ground layer vegetation, which thus greatly influences fire hazard. We used an experimental set-up in greenhouse conditions to study the differences in how (1) fuel moisture and (2) wind velocity influence the ignition probability and fuel consumption among four common circumboreal ground vegetation fuels, Pleurozium schreberi (Willd. ex Brid.) Mitt., Hylocomium splendens Schimp., Dicranum spp. and Cladonia rangiferina (L.) F. H. Wigg. Our results show that the reindeer lichen C. rangiferina was clearly the most flammable species, with high ignition probability even at high moisture contents and low wind velocities. Of the mosses, Dicranum was the least flammable, with low ignition probability and mass loss at low wind velocities regardless of moisture content. P. schreberi and H. splendens behaved somewhat similarly with wind velocities quickly increasing the initially low ignition probability and mass loss observed in the absence of wind. However, especially for mass loss, among-species differences tended to disappear with stronger winds. The observed differences can be explained by the different structures and growth forms of the studied species and open a potential avenue for improving forest fire risk predictions.

Background: Tamoxifen is an established treatment for breast cancer, but its long-term effects on survival and on secondary cancers are not fully evaluated. Material and methods: We studied 30 years outcome of 4124 postmenopausal patients who were randomized to receive (totally) two or five years of adjuvant tamoxifen. Results: After 5 years of follow-up, when tamoxifen treatment was finished in both groups, until 15 years of follow-up, overall mortality (HR 0.80, 95% CI 0.72–0.90, p

Abstract A comprehensive characterization of blood proteome profiles in cancer patients can contribute to a better understanding of the disease etiology, resulting in earlier diagnosis, risk stratification and better monitoring of the different cancer subtypes. Here, we describe the use of next generation protein profiling to explore the proteome signature in blood across patients representing many of the major cancer types. Plasma profiles of 1463 proteins from more than 1400 cancer patients are measured in minute amounts of blood collected at the time of diagnosis and before treatment. An open access Disease Blood Atlas resource allows the exploration of the individual protein profiles in blood collected from the individual cancer patients. We also present studies in which classification models based on machine learning have been used for the identification of a set of proteins associated with each of the analyzed cancers. The implication for cancer precision medicine of next generation plasma profiling is discussed.

Abstract Background Out-of-hospital Emergency Medical Services (OHEMS) require fast and accurate assessment of patients and efficient clinical judgment in the face of uncertainty and ambiguity. Guidelines and protocols can support staff in these situations, but there is significant variability in their use. Therefore, the aim of this study was to increase our understanding of physician decision-making in OHEMS, in particular, to characterize the types of decisions made and to explore potential facilitating and hindering factors. Methods Qualitative interview study of 21 physicians in a large, publicly-owned and operated OHEMS in Croatia. Data was subjected to an inductive content analysis. Results Physicians (mostly young, female, and early in their career), made three decisions (transport, treat, and if yes on either, how) after an initial patient assessment. Decisions were influenced by patient needs, but to a greater extent by factors related to themselves and patients (microsystem), their organization (mesosystem), and the larger health system (macrosystem). This generated a high variability in quality and outcomes. Participants desired support through further training, improved guidelines, formalized feedback, supportive management, and health system process redesign to better coordinate and align care across organizational boundaries. Conclusions The three decisions were made complex by contextual factors that largely lay outside physician control at the mesosystem level. However, physicians still took personal responsibility for concerns more suitably addressed at the organizational level. This negatively impacted care quality and staff well-being. If managers instead adopt a learning orientation, the path from novice to expert physician could be more ably supported through organizational demands and practices aligned with real-world practice. Questions remain on how managers can better support the learning needed to improve quality, safety, and physicians’ journey from novice to expert.

BackgroundFew effective health interventions transition from smaller efficacy or effectiveness studies to real-world implementation at scale, representing a gap between evidence and practice. Recognising this, we have developed Nutrition Now – a tailored digital resource building on four efficacious dietary interventions, aiming to improve nutrition in the important first 1,000 days of life. Nutrition Now targets and guides expectant parents and parents of 0–2 year olds, serves as a reliable source of evidence-based information for midwives and public health nurses at maternal and child healthcare (MCH) centres, and offers pedagogical tools for early childhood education and care (ECEC) staff. The aim of this study is to implement Nutrition Now at scale and evaluate the impact of different sets of multifaceted implementation strategies on implementation outcomes.MethodsA quasi-experimental design with three study arms will be used, providing either low, medium or high implementation support, when rolled out in 50 municipalities in 2 counties in Norway. Nutrition Now will be implemented in MCH and ECEC settings and made available to expectant parents and parents of 0–2 year olds through social media and MCH. The implementation support builds on strategies described in the Expert Recommendations for Implementing Change (ERIC) implementation framework and is informed by dialogues with stakeholders. Impact of the different degree of implementation support will be assessed by examining reach, adoption, fidelity, and sustainability using usage data generated from the Nutrition Now resource, publicly available municipal data and qualitative interviews with MCH and ECEC staff.DiscussionNutrition Now Phase 2 will break new ground by scaling up successively delivered and complementary dietary interventions in the first 1,000 days of life in a real-life context. The project also seeks to identify what level of implementation support is most effective when implementing digital, scalable, evidence-based early-life nutrition interventions in community settings. The project will inform implementation research and provide knowledge about effective implementation strategies to be used in a national scale-up of Nutrition Now.Trial registrationThe study is registered prospectively (submitted 14/06/2022, registration date: 19/06/2022) in the International Standard Randomised Controlled Trial Number registry (ISRCTN): reg. Number: ISRCTN10694967, https://doi.org/10.1186/ISRCTN10694967.

Abstract The utility of spatial immunobiomarker quantitation in prognostication and therapeutic prediction is actively being investigated in triple-negative breast cancer (TNBC). Here, with high-plex quantitative digital spatial profiling, we map and quantitate intraepithelial and adjacent stromal tumor immune protein microenvironments in systemic treatment-naïve (female only) TNBC to assess the spatial context in immunobiomarker-based prediction of outcome. Immune protein profiles of CD45-rich and CD68-rich stromal microenvironments differ significantly. While they typically mirror adjacent, intraepithelial microenvironments, this is not uniformly true. In two TNBC cohorts, intraepithelial CD40 or HLA-DR enrichment associates with better outcomes, independently of stromal immune protein profiles or stromal TILs and other established prognostic variables. In contrast, intraepithelial or stromal microenvironment enrichment with IDO1 associates with improved survival irrespective of its spatial location. Antigen-presenting and T-cell activation states are inferred from eigenprotein scores. Such scores within the intraepithelial compartment interact with PD-L1 and IDO1 in ways that suggest prognostic and/or therapeutic potential. This characterization of the intrinsic spatial immunobiology of treatment-naïve TNBC highlights the importance of spatial microenvironments for biomarker quantitation to resolve intrinsic prognostic and predictive immune features and ultimately inform therapeutic strategies for clinically actionable immune biomarkers.

Abstract Background The use of viscoelastic tests is becoming increasingly popular. There is a paucity of validation of the reproducibility of varying coagulation states. Therefore, we aimed to study the coefficient of variation (CV) for the ROTEM EXTEM parameters clotting time (CT), clot formation time (CFT), alpha-angle and maximum clot firmness (MCF) in blood with varying degrees of coagulation strength. The hypothesis was that CV increases in states of hypocoagulability. Methods Critically ill patients and patients subjected to neurosurgery at a university hospital during three separate periods were included. Each blood sample was tested in eight parallel channels, yielding the CVs for the tested variables. In 25 patients, the blood samples were analysed both at baseline and after dilution with albumin 5%, as well as after being spiked with fibrinogen, simulating weak and strong coagulation. Results In total, 225 unique blood samples were collected from 91 patients. All samples were analysed in eight parallel ROTEM channels, resulting in 1,800 measurements. In hypocoagulable samples, defined as those with values outside the normal reference range, the CV of CT was higher (median (interquartile range)) (6.3% (5.1–9.5)) than for normocoagulable samples (5.1% (3.6–7.5)), p

Bladder cancer is a heterogenous disease, and molecular subtyping is a promising method to capture this variability. Currently, the immune compartment in relation to subtypes is poorly characterized. Here, we analyzed the immune compartment in bladder tumors and normal bladder urothelium with a focus on T cell subpopulations using flow cytometry and RNA sequencing. The results were investigated in relation to tumor invasiveness (NMIBC/MIBC) and molecular subtypes according to the Lund Taxonomy system. Whereas the NMIBC/MIBC differed in the overall immune infiltration only, the molecular subtypes differed both in terms of immune infiltration and immune compartment compositions. The Basal/Squamous (Ba/Sq) and genomically unstable (GU) tumors displayed increased immune infiltration compared to urothelial-like (Uro) tumors. Additionally, the GU tumors had a higher proportion of regulatory T cells within the immune compartment compared to Uro tumors. Furthermore, sequencing showed higher levels of exhaustion in CD8+ T cells from GU tumors compared to both Uro tumors and the control. Although no such difference was detected at the transcriptomic level in Uro tumors compared to the controls, CD8+ T cells in Uro tumors showed higher expression of several exhaustion markers at the protein level. Taken together, our findings indicate that depending on the molecular subtype, different immunotherapeutic interventions might be warranted.

The personalization of therapies in breast cancer has favoured the introduction of new molecular-targeted therapies into clinical practice. Among them, cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors have acquired increasing importance, with the approval in recent years of palbociclib, ribociclib, and abemaciclib in combination with endocrine therapy. Currently, no guidelines are available to monitor and manage potential long-term toxicities associated with the use of these drugs. A multidisciplinary panel of European oncologists, was supported by a pharmacologist, a hematologist, a hepatologist and a pulmonologist to discuss the management of long-term toxicities, based on the literature review and their clinical experience. The panel provided detailed roadmaps to manage long-term toxicities associated with the use of CDK4/6 inhibitors in clinical practice. Knowing the frequency and characteristics of the toxicity profile associated with each CDK4/6 inhibitor is important in the decision-making process to match the right drug to the right patient.

BackgroundThe appropriate time to discontinue chemotherapy at the end of life has been widely discussed. In contrast, few studies have investigated the patterns of endocrine treatment near death. In this study, we aimed to investigate the end-of-life endocrine treatment patterns of older women with metastatic breast cancer and explore characteristics associated with treatment.MethodsA retrospective cohort study of all older women (age ≥65 years) with hormone receptor-positive breast cancer who died in Sweden, 2016 − 2020. We used routinely collected administrative and health data with national coverage. Treatment initiation was defined as dispensing during the last three months of life with a nine-month washout period, while continuation and discontinuation were assessed by previous use during the same period. We used log-binomial models to explore factors associated with the continuation and initiation of endocrine treatments.ResultsWe included 3098 deceased older women with hormone receptor-positive breast cancer (median age 78). Overall, endocrine treatment was continued by 39% and initiated by 5% and of women during their last three months of life, while 31% discontinued and 24% did not use endocrine treatment during their last year of life. Endocrine treatment continuation was more likely among older and less educated women, and among women who had multi-dose drug dispensing, chemotherapy, and CDK4/6 use. Only treatment-related factors were associated with treatment initiation.ConclusionMore than a third of women with metastatic breast cancer continue endocrine treatments potentially past the point of benefit, whereas late initiation is less frequent. Further research is warranted to determine whether our results reflect overtreatment at the end of life once patients’ preferences and survival prognosis are considered.

Abstract Background Longitudinal, real-world data on the management of metastatic breast cancer is increasingly relevant to understand breast cancer care in routine clinical practice. Yet such data are scarce, particularly beyond second- and third-line treatment strategies. This study, therefore, examined both the long-term treatment patterns and overall survival (OS) in a regional Swedish cohort of female patients with metastatic breast cancer stratified by subtype in routine clinical practice during a recent eight-year period and correlation to current treatment guidelines. Methods Consecutive female patients with metastatic breast cancer clinically managed at Uppsala University Hospital, Uppsala, Sweden, during 2009–2016 and followed until the end of September, 2017 (n = 370) were included and, where possible, classified as having one of five, intrinsic subtypes: Luminal A; Luminal B; human epidermal growth factor receptor 2-positive (HER2+)/ estrogen receptor-positive (ER+); HER2+/estrogen receptor-negative (ER-); or triple negative breast cancer (TNBC). Treatment patterns and OS were estimated by subtype using time-to-event methods. Results A total of 352/370 patients with metastatic breast cancer (mean age 67.6 years) could be subtyped: 118 (34%) were Luminal A, 119 (34%) Luminal B, 31 (8%) HER2+/ER-, 38 (11%) HER2+/Luminal, and 46 (13%) TNBC. The median number of metastatic treatment lines was 3. Most patients were on active treatment during follow-up (80% of the observation period), except for patients with TNBC who were on treatment for 60% of the observation time. Overall, 67% of patients died whilst on treatment. Among all patients (n = 370), median OS was 32.5 months (95% CI = 28.2–35.7). The 5-year survival rate was highest for HER2+/Luminal (46%) patients, followed by Luminal B (29%), Luminal A (28%), HER2+/ER- (21%), and TNBC (7%). Increasing age and number of metastatic sites also predicted worse survival. Conclusions Metastatic breast cancer patients in Sweden, irrespective of subtype, generally receive active treatment until time of death. Survival varies considerably across subtypes and is also associated with patient characteristics. Regardless of differences in treatment patterns for Luminal A and B patients, long-term OS was the same.