Impact of Prosigna test on adjuvant treatment decision in lymph node-negative early breast cancer-a prospective national multicentre study (EMIT-1).

BACKGROUND: EMIT-1 is a national, observational, single-arm trial designed to assess the value of the Prosigna, Prediction Analysis of Microarray using the 50 gene classifier (PAM50)/Risk of Recurrence (ROR), test as a routine diagnostic tool, examining its impact on adjuvant treatment decisions, clinical outcomes, side-effects and cost-effectiveness. Here we present the impact on treatment decisions. PATIENTS AND METHODS: Patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative pT1-pT2 lymph node-negative early breast cancer (EBC) were included. The Prosigna test and standard histopathology assessments were carried out. Clinicians' treatment decisions were recorded before (pre-Prosigna) and after (post-Prosigna) the Prosigna test results were disclosed. RESULTS: Of 2217 patients included, 2178 had conclusive Prosigna results. The pre-Prosigna treatment decisions were: no systemic treatment (NT) in 27% of patients, endocrine treatment alone (ET) in 38% and chemotherapy (CT) followed by ET (CT + ET) in 35%. Post-Prosigna treatment decisions were 25% NT, 51% ET and 24% CT + ET, respectively. Adjuvant treatment changed in 28% of patients, including 21% change in CT use. Among patients assigned to CT + ET pre-Prosigna, 45% were de-escalated to ET post-Prosigna. Of patients assigned to ET, 12% were escalated to CT + ET and 8% were de-escalated to NT; of those assigned to NT, 18% were escalated to ET/CT + ET. CT was more frequently recommended for patients aged ≤50 years. In the subgroup with pT1c-pT2 G2 and intermediate Ki67 (0.5-1.5× local laboratory median Ki67 score), the pre-Prosigna CT treatment decision varied widely across hospitals (3%-51%). Post-Prosigna, the variability of CT use was markedly reduced (8%-24%). The correlation between Ki67 and ROR score within this subgroup was poor (r = 0.25-0.39). The median ROR score increased by increasing histological grade, but the ROR score ranges were wide (for G1 0-79, G2 0-90, G3 16-94). CONCLUSION: The Prosigna test result changed adjuvant treatment decisions in all EBC clinical risk groups, markedly decreased the CT use for patients categorized as higher clinical risk pre-Prosigna and reduced treatment decision discrepancies between hospitals.

The feasibility of a multidimensional intervention in lymphoma survivors with chronic fatigue.

PURPOSE: Chronic fatigue (CF) affects 25-30% of lymphoma survivors, but interventions designed to reduce fatigue are lacking. The main aim of this study was to test the feasibility of a multidimensional intervention study in lymphoma survivors with CF. Secondary aims were to describe individual changes in fatigue, quality of life (QoL) and physical performance from pre (T0) to post (T1) intervention. METHODS: This feasibility study was as a one-armed intervention study performed in 2021. Hodgkin or aggressive non-Hodgkin lymphoma survivors received mailed study information and Chalder Fatigue Questionnaire and were asked to respond if they suffered from fatigue. The 12-week intervention included patient education, physical exercise, a cognitive behavioural therapy (CBT)-based group program and nutritional counselling. Feasibility data included patient recruitment, completion of assessments, adherence to the intervention and patient-reported experience measures. Participants responded to questionnaires and underwent physical tests at T0 and T1. RESULTS: Seven lymphoma survivors with CF were included. Of all assessments, 91% and 83% were completed at T0 and T1, respectively. Adherence to the interventional components varied from 69% to 91%. At T1, all participants rated exercise as useful, of whom five rated the CBT-based program and five rated individual nutritional counselling as useful. Five participants reported improved fatigue, QoL and physical performance. CONCLUSION: Lymphoma survivors with CF participating in a multidimensional intervention designed to reduce the level of fatigue showed high assessment completion rate and intervention adherence rate. Most of the participants evaluated the program as useful and improved their level of fatigue, QoL and physical performance after the intervention. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT04931407. Registered 16. April 2021-Retrospectively registered. https://www. CLINICALTRIALS: gov/ct2/show/NCT04931407.

Norwegian general population normative data for the European Organization for Research and Treatment of Cancer questionnaires: the Quality of Life Questionnaire-Core 30, the Sexual Health Questionnaire QLQ-SHQ22 and the sexual domains of the QLQ-BR23/BR45.

OBJECTIVE: The aim of this study was to provide sex-, age-, and morbidity-specific Norwegian general population normative values for the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires QLQ-C30, the sexual health questionnaire QLQ-SHQ22 and the sexual domains of the breast modules QLQ-BR23 and QLQ-BR45. METHODS: A random nationwide sample stratified by sex and age groups (18-29, 30-39, 40-49, 50-59, 60-69 and ≥70 years) was drawn from the Norwegian National Population Register. Participants were notified through national online health services (HelseNorge) and postal mail. The survey included sociodemographic background information, health-related quality of life assessed by the EORTC questionnaires, and morbidity assessed by the Self-Administered Comorbidity Questionnaire. Multivariable linear regression was carried out to estimate the associations of age, sex and morbidity with the EORTC scale and item scores. RESULTS: Of the 15,627 eligible individuals, 5135 (33%) responded. Women and persons with morbidities reported lower functioning and higher symptom burden than men and persons without morbidities, respectively, on nearly all EORTC scales. Sex differences were most prominent for emotional functioning, pain, fatigue and insomnia (QLQ-C30), body image, sexual functioning (QLQ-BR23/45), importance of sexual activity, libido and fatigue (QLQ-SHQ22). The score differences between persons with and without morbidity were highly significant and largest in the youngest and middle-aged groups. CONCLUSION: This is the first study to provide normative values for the EORTC sexual health questionnaire QLQ-SHQ22 and the sexual subscales of the QLQ-BR23 and QLQ-BR45 for all, separately in age groups by sex and morbidity.

Work ability 8 years after breast cancer: exploring the role of social support in a nation-wide survey.

INTRODUCTION: As the 5-year survival rate after breast cancer in Norway is 92%, the population of breast cancer survivors (BCSs) is increasing. Knowledge of work ability in this population is scarce. In a population-based cohort of BCSs, we explored work ability 8 years after diagnosis and the association between work ability and social support, and cancer-related variables including late effects and lifestyle factors. METHODS: In 2019, all Norwegian women < 59 years when diagnosed with stage I-III breast cancer in 2011 or 2012, were identified by the Cancer Registry of Norway and invited to participate in a survey on work life experiences. Work ability was assessed using the Work Ability Index (scale 0-10). Factors associated with excellent work ability (score ≥ 9) were identified using univariate and multivariate logistic regression analyses, and adjusted for socioeconomic-, health- and cancer-related variables. RESULTS: Of the 1951 eligible BCSs, 1007 (52.8%) responded. After excluding survivors with relapse (n = 1), missing information on work ability score (n = 49), or work status (n = 31), the final sample comprised 926 BCSs within working age at survey (< 67 years). Mean age at survey was 56 years and 8 years (SD 0.7) had passed since diagnosis. Work ability had been reduced from 8.9 (SD 2.3) at diagnosis to 6.3 (SD 3.1). One in three BCSs reported poor work ability (WAS ≤ 5), and seven out of ten reported that their physical work ability had been reduced due to cancer. Social support from colleagues during cancer therapy was associated with excellent work ability, which was not observed for social support provided by supervisors or the general practitioner. Cognitive impairment and fatigue were inversely associated with work ability. None of the cancer-related variables, including treatment, were associated with work ability 8 years after diagnosis. CONCLUSION: In this population-based sample, one in three BCSs reported poor work ability 8 years after diagnosis. Collegial social support during cancer therapy appears to be a protective factor for sustained work ability, whilst survivors struggling with fatigue and cognitive impairments may represent a particularly vulnerable group for reduced work ability.

Work status changes and associated factors in a nationwide sample of Norwegian long-term breast cancer survivors.

PURPOSE: The study aims to describe work status at diagnosis and 8 years post-diagnosis in a nationwide sample of breast cancer survivors (BCSs), and investigate associated and self-reported factors of reduced work status. METHODS: Women aged 20-65 years when diagnosed with stage I-III breast cancer (BC) in 2011 or 2012 were invited to participate in a questionnaire study in 2019 (n = 2803), of whom 49% (n = 1361) responded. For this sub-study, we included 974 BCSs below the legal retirement age in Norway (< 67 years) at survey and with complete work status data. Reduced work status was defined as being in paid work at BC diagnosis and not working at time of survey. Logistic regression analyses were applied to identify factors associated with reduced work status. RESULTS: Of BCSs who were in paid work at diagnosis (n = 845), 63% maintained their work status to 8 years later. Reduced work status was associated with not living with children (OR .44, 95% CI .24-.82), age (OR 1.16, 95% CI 1.11-1.21), chemotherapy (OR 2.83, 95% CI 1.24-6.61), > 2 comorbid conditions (OR 2.27, 95% CI 1.16-4.32), cognitive function (OR .99, 95% CI .98-.99), fatigue (OR 1.02, 95% CI 1.01-1.03), and neuroticism (OR 1.57, 95% CI 1.00-2.46). BC and late effects were reported as reasons for reduced work status and disability. CONCLUSIONS: The majority of BCSs who were in paid work at diagnosis were working 8 years later. IMPLICATIONS FOR CANCER SURVIVORS: Our results suggest a need to focus on fatigue and reduced cognitive function among long-term BCSs, with the ultimate aim of improving work sustainability.

Dose distribution in the thyroid gland following radiation therapy of breast cancer--a retrospective study.

PURPOSE: To relate the development of post-treatment hypothyroidism with the dose distribution within the thyroid gland in breast cancer (BC) patients treated with loco-regional radiotherapy (RT). METHODS AND MATERIALS: In two groups of BC patients postoperatively irradiated by computer tomography (CT)-based RT, the individual dose distributions in the thyroid gland were compared with each other; Cases developed post-treatment hypothyroidism after multimodal treatment including 4-field RT technique. Matched patients in Controls remained free for hypothyroidism. Based on each patient's dose volume histogram (DVH) the volume percentages of the thyroid absorbing respectively 20, 30, 40 and 50 Gy were then estimated (V20, V30, V40 and V50) together with the individual mean thyroid dose over the whole gland (MeanTotGy). The mean and median thyroid dose for the included patients was about 30 Gy, subsequently the total volume of the thyroid gland (VolTotGy) and the absolute volumes (cm3) receiving respectively <30 Gy and ≥30 Gy were calculated (Vol<30 and Vol≥30) and analyzed. RESULTS: No statistically significant inter-group differences were found between V20, V30, V40 and V50Gy or the median of MeanTotGy. The median VolTotGy in Controls was 2.3 times above VolTotGy in Cases (ρ=0.003), with large inter-individual variations in both groups. The volume of the thyroid gland receiving<30 Gy in Controls was almost 2.5 times greater than the comparable figure in Cases. CONCLUSIONS: We concluded that in patients with small thyroid glands after loco-radiotherapy of BC, the risk of post-treatment hypothyroidism depends on the volume of the thyroid gland.

Alterations of gene expression in blood cells associated with chronic fatigue in breast cancer survivors.

Fatigue is one of the most frequent complaints among breast cancer survivors. However, mechanisms underlying persisting fatigue after end of treatment are poorly understood. To explore whether biological processes underlying persistent fatigue can affect gene expression of blood cells, genome-wide expression analyses were performed on whole blood samples from breast cancer survivors classified as chronic fatigued 2-6 years after diagnosis. Non-fatigued survivors served as controls. Several gene sets involved in plasma- and B-cell pathways differed between the chronic fatigued and the non-fatigued, suggesting that a dysregulation in these pathways is associated with chronic fatigue and that a B-cell-mediated inflammatory process might underlie fatigue. The chronic fatigued also had a higher level of leucocytes, lymphocytes and neutrophiles compared with the non-fatigued, thus further indicating that an activation of the immune system plays a role in the biology of chronic fatigue in breast cancer survivors.

[Living and dying alone. An epidemiological study of deaths outside institutions in Oslo in 1989]. / A leve og dø alene. En epidemiologisk undersøkelse av dødsfall utenfor institusjon i Oslo i 1989.

This study is based on data on autopsies performed at the Institute of Forensic Medicine, National Hospital, Oslo, in 1989. Solitary men and women were compared with non-solitary men and women with respect to causes of death and manner of death. Solitary men died more often from potentially curable diseases, especially pneumonia. These individuals had often suffered from chronic alcoholism and had lived in central Oslo. Among women there were no differences in the causes of death of solitary and non-solitary individuals.

Role of chloride/bicarbonate antiport in the control of cytosolic pH. Cell-line differences in activity and regulation of antiport.

Sodium-linked and sodium-independent HCO3-/Cl- antiport was measured under different conditions in a number of cell lines. Transport of HCO3- was estimated from its effect on intracellular pH (pHi) measured with the fluorescent probe 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein. The associated ion fluxes were estimated from the transport of 36Cl- and 22Na+. Na+-dependent and Na+-independent HCO3-/Cl- antiport were found in many, but not in all cell lines tested. The Na+-independent HCO3-/Cl- antiport was found to be highly pHi-dependent in a number of cell lines, whereas in others this was not the case. Some cell lines were found to have both Na+-dependent and Na+-independent HCO3-/Cl- antiport, whereas in others we could detect only one of these mechanisms. Na+/H+ antiport, which is quantitatively the most important H+-extruding mechanism, was found in all cell lines tested, but the activity varied strongly. Possible reasons for the qualitative and quantitative differences in antiport activity are discussed.