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Abstract 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.

Background: Although anthracycline-related cardiotoxicity is widely studied, only a limited number of echocardiographic studies have assessed cardiac function in breast cancer survivors (BCSs) beyond ten years from anthracycline treatment, and the knowledge of long-term cardiorespiratory fitness (CRF) in this population is scarce. This study aimed to compare CRF assessed as peak oxygen uptake (V̇O 2 ), cardiac morphology and function, and cardiovascular (CV) risk factors between long-term BCSs treated with anthracyclines and controls with no history of cancer., Methods: The CAUSE (Cardiovascular Survivors Exercise) trial included 140 BCSs recruited through the Cancer Registry of Norway, who were diagnosed with breast cancer stage II to III between 2008 and 2012 and had received treatment with epirubicin, and 69 similarly aged activity level-matched controls. All the participants underwent blood sampling, blood pressure measurements, echocardiography and cardiopulmonary exercise testing from October 2020 to August 2022., Results: BCSs were aged 59 ± 6 years and had received a cumulative dose of 357 (243 to 366) mg/m 2 of epirubicin on average 11 ± 1 years before inclusion. There was no difference between BCSs and controls with respect to peak V̇O 2 (27.6 ± 5.4 mL/kg/min vs. 27.1 ± 5.4 mL/kg/min, P = 0.25), 2D left ventricular ejection fraction (57 ± 3% vs. 57 ± 3%, P = 0.43), left ventricular global longitudinal strain (-20.5 ± 1.0% vs. -20.6 ± 1.0%, P = 0.46) or the proportion with N-terminal pro-brain natriuretic peptide ≥ 125 (22% vs. 20%, P = 0.93). The proportions with hypertension, dyslipidemia or diabetes did not differ between the groups., Conclusion: We found that CRF, cardiac function, and CV risk profile in BCSs examined a decade after treatment with anthracyclines were similar to that in women with no history of cancer., Trial Registration: clinicaltrials.gov (NCT04307407) https://clinicaltrials.gov/ct2/show/NCT04307407 ., Competing Interests: Declarations. Ethical approval: Written informed consent was given by all study participants. The study complies with the Declaration of Helsinki and was approved by the Regional Committees for Medical and Health Research Ethics (2019/1318) and the Data Protection Services for Research (865175). Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Breast cancer is the most commonly occurring form of cancer in pregnancy. Among women aged between 25 and 29 years, one in five cases of breast cancer will occur in pregnancy or during the first postnatal year. The prevalence is increasing, presumably because of the increase in maternal age at pregnancy. Interdisciplinary cooperation is needed to ensure a good outcome for both mother and child. The prognosis is good but depends on rapid diagnosis and optimal treatment. In this clinical review article, the most important aspects of breast cancer treatment during pregnancy are reviewed.

Purpose: A breast cancer (BC) diagnosis may negatively affect health-related quality of life (HRQoL). However, there are few comparisons of HRQoL at several time points for women with BC, and particular when subdivided into invasive and in situ tumors. The purpose of this study was to investigate various aspects of HRQoL in women recently diagnosed with invasive BC or ductal carcinoma in situ (in situ) compared to age-matched BC free controls in a population-wide sample recruited through the Cancer Registry of Norway., Methods: This cross-sectional study utilized HRQoL data collected in 2020-2022 from a digital survey including 4117 cases (3867 women with invasive BC and 430 with in situ) and 2911 controls. HRQoL was assessed ≥ 21 days after diagnosis, using EORTC QLQ-C30. This includes scores assessing global quality of life (gHRQoL) and HRQoL functions and symptoms. Multivariable regression analyses were used to compare HRQoL between cases and controls and to identify factors associated with gHRQoL and fatigue. Additionally, HRQoL 14 months after diagnosis was analyzed in 1989 of the included cases and in 1212 of the controls. Score differences of ≥ 10 points were considered clinically relevant and thus presented in the results., Results: Invasive BC cases had lower gHRQoL, role- and social functioning in addition to more fatigue than controls. In situ cases had lower role-and social functioning than controls. Invasive BC cases scored worse than in situ on all domains, but the differences were not considered clinically relevant. Physical activity was associated with better gHRQoL and less fatigue in invasive BC, in situ and controls. Both invasive BC and in situ cases improved their role- and social functioning scores from diagnosis to 14 months follow-up, however no improvement was seen for fatigue., Conclusion: Women with invasive BC and in situ reported lower role- and social functioning scores than controls right after diagnosis with improvements 14 months after diagnosis. Physical activity was associated with better gHRQoL and less fatigue and should, whenever possible, play a key role in the care for BC patients., (© 2024. The Author(s).)

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., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Little is known about how health-related quality of life (HRQoL) in breast cancer cases differed from that of controls during and after the COVID-19 pandemic. This study used data from an ongoing, nationwide HRQoL survey of 4279 newly diagnosed breast cancer cases and 2911 controls to investigate how breast cancer patients fared during different phases of the pandemic compared to controls. Responders during 2020-2022 were categorized into three COVID-19-related phases: the social restrictions phase, the high infection rate phase, and the post-pandemic phase. Across phases, breast cancer cases had significantly worse scores in most HRQoL domains compared to controls. Apart from slightly more insomnia in the high infection rate phase for both cases and controls, and better social functioning for young cases in the post-COVID-19 phase, the case-control differences in HRQoL remained consistent across phases. When the phases were assessed as one period, young women and those living with children <18 years of age fared the worst among breast cancer cases, while single women fared the worst among controls. In contrast, controls living with children <18 years of age exhibited better HRQoL than controls without children. In summary, women with breast cancer did not appear to fare differently than controls in terms of HRQoL across COVID-19 phases. However, breast cancer cases with young children fared worse in their HRQoL than other breast cancer cases.

Breast cancer is the most common cancer among women in Norway. Nine out of ten will become long-term survivors. Being cancer-free does not necessarily mean feeling healthy, and many experience troublesome late effects, such as fatigue, pain and fear of recurrence. General practitioners represent the most important medical support for the majority of these women. This clinical review article summarises up-to-date knowledge about late effects after breast cancer treatment. Non-pharmacological interventions can have a positive effect on many of the most common late effects.

Background: One-third or more of breast cancer survivors report stress and other psychological and physical complaints that can negatively impact their quality of life. Psychosocial stress management interventions, shown to mitigate the negative impact of these complaints, can now be delivered as accessible and convenient (for the patient and provider) eHealth interventions. In this randomized controlled trial (RCT), Coping After Breast Cancer (CABC), 2 modified versions of the stress management eHealth intervention program StressProffen were created: one with predominantly cognitive behavioral stress management content (StressProffen-cognitive behavioral therapy intervention [StressProffen-CBI]) and another with predominantly mindfulness-based stress management content (StressProffen-mindfulness-based intervention [StressProffen-MBI])., Objective: This study aims to investigate the effects in breast cancer survivors of using StressProffen-CBI and StressProffen-MBI compared with a control group (treatment as usual)., Methods: Women diagnosed with breast cancer (stage I-III, unequivocally human epidermal growth factor receptor 2-positive or estrogen receptor-negative tumors) or ductal carcinoma in situ (DCIS) aged 21-69 years who completed the Cancer Registry of Norway-initiated health survey on quality of life are invited to the CABC trial about 7 months after diagnosis. Women who give consent to participate are randomized (1:1:1) to either the StressProffen-CBI, StressProffen-MBI, or control group. Both StressProffen interventions consist of 10 modules of stress management content delivered through text, sound, video, and images. The primary outcome is between-group changes in perceived stress at 6 months, assessed with Cohen 10-item Perceived Stress Scale. The secondary outcomes comprise changes in quality of life, anxiety, depression, fatigue, sleep, neuropathy, coping, mindfulness, and work-related outcomes approximately 1, 2, and 3 years after diagnosis. Long-term effects of the interventions on work participation, comorbidities, relapse or new cancers, and mortality will be assessed using data from national health registries., Results: Recruitment is scheduled from January 2021 to May 2023. The goal is to recruit 430 participants (100 in each group). As of April 14 2023, 428 participants have been enrolled., Conclusions: The CABC trial is possibly the largest ongoing psychosocial eHealth RCT in patients with breast cancer. If 1 or both interventions prove to be effective in reducing stress and improving psychosocial and physical complains, the StressProffen eHealth interventions could be beneficial, inexpensive, and easily implementable tools for breast cancer survivors when coping with late effects after cancer and cancer treatments., Trial Registration: Clinicaltrials.gov NCT04480203; https://clinicaltrials.gov/ct2/show/NCT04480203., International Registered Report Identifier (irrid): DERR1-10.2196/47195., (©Karianne Svendsen, Lise Solberg Nes, Anders Meland, Ine Marie Larsson, Ylva M Gjelsvik, Elin Børøsund, Christine M Rygg, Tor Åge Myklebust, Kristin V Reinertsen, Cecilie E Kiserud, Helle Skjerven, Michael H Antoni, Trudie Chalder, Ingvil Mjaaland, Linda E Carlson, Hege R Eriksen, Giske Ursin. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 24.05.2023.)

Objective: Breast cancer and breast cancer-directed radiation therapy (RT) may increase the risk of late effects, such as hypothyroidism. We conducted a systematic review and meta-analysis to investigate the association between breast cancer, RT, and risk of hypothyroidism in breast cancer survivors., Methods: Through February 2022, we searched PubMed, EMBASE, and references of relevant articles, to identify papers on breast cancer and breast cancer-directed RT and subsequent risk of hypothyroidism. Articles were screened by title and abstract and reviewed for eligibility. We used a pre-formed data extraction sheet and identified key design elements that could potentially introduce bias. The main outcome was the confounder-adjusted relative risk (RR) of hypothyroidism in breast cancer survivors versus women without breast cancer, and in breast cancer survivors according to the receipt of RT to the supraclavicular lymph nodes. We used a random-effects model to calculate pooled RRs and associated 95% confidence intervals (95% CI)., Results: From 951 papers screened by title and abstract, 34 full-text papers were reviewed for eligibility. We included 20 studies published between 1985 and 2021-19 were cohort studies. Compared with women without breast cancer, the pooled RR of hypothyroidism in breast cancer survivors was 1.48 (95% CI: 1.17, 1.87), with highest risk associated with RT to the supraclavicular region (RR = 1.69, 95% CI: 1.16, 2.46). The most important limitations of the studies were small sample size yielding estimates with low precision, and lack of data on potential confounders., Conclusion: Breast cancer and radiation therapy to the supraclavicular lymph nodes is associated with an increased risk of hypothyroidism., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Anthracycline-based chemotherapy has been mainstay of adjuvant breast cancer therapy for decades. Although effective, anthracyclines place long-term breast cancer survivors at risk of late effects, such as reduced cardiorespiratory fitness and increased risk of cardiovascular disease. Previous research has shown beneficial effects of exercise training on cardiorespiratory fitness, but the effects of exercise on limiting factors for cardiorespiratory fitness, cardiovascular risk factors, and patient-reported outcomes in long-term survivors are less clear. Whether previous exposure to breast cancer therapy modulates the effects of exercise is also unknown., Objective: The primary aim of the CAUSE (Cardiovascular Survivors Exercise) trial is to examine the effect of aerobic exercise on cardiorespiratory fitness in anthracycline-treated long-term breast cancer survivors. Secondary aims are to examine effects of exercise training on limiting factors for cardiorespiratory fitness, cardiovascular risk factors, and patient-reported outcomes, and to compare baseline values and effects of exercise training between similar-aged women with and those without prior breast cancer. A third aim is to examine the 24-month postintervention effects of aerobic exercise on primary and secondary outcomes., Methods: The CAUSE trial is a 2-armed randomized controlled trial, where 140 long-term breast cancer survivors, 8-12 years post diagnosis, are assigned to a 5-month nonlinear aerobic exercise program with 3 weekly sessions or to standard care. Seventy similar-aged women with no history of cancer will undergo the same exercise program. Cardiorespiratory fitness measured as peak oxygen consumption (VO 2peak ), limiting factors for VO 2peak (eg, cardiac function, pulmonary function, hemoglobin mass, blood volume, and skeletal muscle characteristics), cardiovascular risk factors (eg, hypertension, diabetes, dyslipidemia, obesity, physical activity level, and smoking status), and patient-reported outcomes (eg, body image, fatigue, mental health, and health-related quality of life) will be assessed at baseline, post intervention, and 24 months post intervention., Results: A total of 209 patients were included from October 2020 to August 2022, and postintervention assessments were completed in January 2023. The 24-month follow-up will be completed in February 2025., Conclusions: The findings from the CAUSE trial will provide novel scientific understanding of the potential benefits of exercise training in long-term breast cancer survivors., Trial Registration: ClinicalTrials.gov NCT04307407; https://clinicaltrials.gov/ct2/show/NCT04307407., International Registered Report Identifier (irrid): DERR1-10.2196/45244., (©Tormod Skogstad Nilsen, Mali Sæter, Sebastian Imre Sarvari, Kristin Valborg Reinertsen, Sara Hassing Johansen, Elisabeth Rustad Edvardsen, Jostein Hallén, Elisabeth Edvardsen, May Grydeland, Cecilie Essholt Kiserud, Hanne Cathrine Lie, Paul André Solberg, Torbjørn Wisløff, Adam Philip Sharples, Truls Raastad, Kristina Hermann Haugaa, Lene Thorsen. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 15.03.2023.)

Neuroticism is a basic personality trait concerning negative feelings under stressful conditions. Our purpose was to examine the rate of high neuroticism and factors associated with high neuroticism in long-term (≥ 5 years) survivors of childhood, adolescent, and young adult cancer (CAYACSs). Norwegian CAYACSs aged 0-39 years when diagnosed and treated between 1985 and 2009 for cancer in childhood/adolescence (0-18 years), or as young adults (19-39 years) and alive in 2015 were mailed a questionnaire. Data from 1629 CAYACSs (481 children/adolescents and 1148 young adults) were analyzed. High neuroticism was found in 44% of survivors of childhood/adolescent cancers versus 34% in survivors of young adult cancer (p < 0.001). The rate of high neuroticism in female CAYACSs was 40% and in males 30% (p < 0.001). The corresponding difference between male survivor group was non-significant. In multivariable analysis, young age at survey, more adverse effects, poor self-rated health, female sex, chronic fatigue, and increased depression remained significantly associated with high neuroticism. Cancer treatment, comorbidity, and lifestyle were significant in bivariate analyses. Cancer at earlier age could increase the risk of high neuroticism among adult survivors. Screening for neuroticism could identify CAYACSs at risk for experiencing multiple health concerns and needing special follow-up attention., (© 2022. The Author(s).)

Background: A major depressive episode (MDE) is typically self-rated by screening forms identifying probable MDE (pMDE). This population-based cross-sectional questionnaire study examined the prevalence rates of pMDE identified by the PHQ-9 screener in long-term survivors of childhood and adolescence (CACSs) and young adult cancer (YACSs) and a normative sample (NORMs)., Methods: Data from 488 CACSs, 1202 YACSs, and 1453 NORMs were analyzed, and pMDE was defined both by cut-off ≥10 on the total PHQ-9 score and by an algorithm., Results: The prevalence rates of pMDE among CACSs were 21.5%, 16.6% in YACSs, and 9.2% among NORMs using the cut-off definition. With the algorithm, the prevalence rates of pMDE were 8.0% among CACSs, 8.1% among YACSs, and 3.9% among NORMs. Independent of definition, CACSs and YACSs had significantly increased prevalence rates of pMDE compared to NORMs. Psychosocial factors and self-rated health were significantly associated with both definitions of pMDE in multivariable analyses, while survivor groups, cancer types, and adverse events were not., Conclusion: Since pMDE has negative health consequences and is amenable to treatment, healthcare providers should be attentive and screen for pMDE in young cancer survivors. For PHQ-9, the preferred type of definition of pMDE should be determined.

Background: In breast cancer, immunohistochemistry (IHC) subtypes, together with grade and stage, are well-known independent predictors of breast cancer death. Given the immense changes in breast cancer treatment and survival over time, we used recent population-based data to test the combined influence of IHC subtypes, grade and stage on breast cancer death., Methods: We identified 24,137 women with invasive breast cancer aged 20 to 74 between 2005 and 2015 in the database of the Cancer Registry of Norway. Kaplan-Meier curves, mortality rates and adjusted hazard ratios for breast cancer death were estimated by IHC subtypes, grade, tumour size and nodal status during 13 years of follow-up., Results: Within all IHC subtypes, grade, tumour size and nodal status were independent predictors of breast cancer death. When combining all prognostic factors, the risk of death was 20- to 40-fold higher in the worst groups compared to the group with the smallest size, low grade and ER+PR+HER2- status. Among node-negative ER+HER2- tumours, larger size conferred a significantly increased breast cancer mortality. ER+PR-HER2- tumours of high grade and advanced stage showed particularly high breast cancer mortality similar to TNBC. When examining early versus late mortality, grade, size and nodal status explained most of the late (> 5 years) mortality among ER+ subtypes., Conclusions: There is a wide range of risks of dying from breast cancer, also across small breast tumours of low/intermediate grade, and among node-negative tumours. Thus, even with modern breast cancer treatment, stage, grade and molecular subtype (reflected by IHC subtypes) matter for prognosis.

Background: Breast cancer survivors (BCS) may have increased risk of hypothyroidism, but risk according to treatment modality is unclear. We estimated the incidence of hypothyroidism in women with breast cancer, and according to cancer treatment., Methods: Using nationwide registries, we identified all Danish women aged ≥ 35 years diagnosed with non-metastatic breast cancer (1996-2009). We matched up to five cancer-free women (controls) for each BCS. We excluded women with prevalent thyroid disease. Cancer treatment was chemotherapy with or without radiotherapy (RT) targeting the breast/chest wall only, or also the lymph nodes (RTn). We identified hypothyroidism using diagnostic codes, and/or levothyroxine prescriptions. We calculated the cumulative incidence, incidence rates (IR) per 1000 person-years, and used Cox regression to estimate hazard ratios (HR) and associated 95% confidence intervals (CIs) of hypothyroidism, adjusting for comorbidities., Results: We included 44,574 BCS and 203,306 matched controls with 2,631,488 person-years of follow-up. BCS had a slightly higher incidence of hypothyroidism than controls [5-year cumulative incidence, 1.8% (95%CI = 1.7-1.9) and 1.6% (95%CI = 1.5-1.6), respectively]. The overall IR was 4.45 (95%CI = 4.25-4.67) and 3.81 (95%CI = 3.73-3.90), corresponding to an adjusted HR = 1.17 (95%CI = 1.11-1.24). BCS who received RTn with chemotherapy (HR = 1.74, 95%CI = 1.50-2.02) or without chemotherapy (HR = 1.31, 95%CI = 1.14-1.51) had an elevated risk of hypothyroidism compared with matched controls and compared with BCS who underwent surgery alone [HR = 1.71, 95%CI = 1.45-2.01 and HR = 1.36, 95%CI = 1.17-1.58, respectively]., Conclusions: BCS have an excess risk of hypothyroidism compared with age-matched controls. BCS and those working in cancer survivorship settings ought to be aware that this risk is highest in women treated with radiation therapy to the lymph nodes and chemotherapy.

Background: Hypothyroidism may occur as a late effect of breast cancer-directed treatment, particularly after radiotherapy, but little is known whether hypothyroidism affects the prognosis after breast cancer. We investigated the association between hypothyroidism and breast cancer recurrence, and all-cause mortality., Methods: In this population-based cohort study, we used national medical registries to identify all Danish women 35 years or older diagnosed with stage I-III, operable breast cancer between 1996 and 2009. Hypothyroidism was defined as hospital diagnoses ascertained via diagnostic codes, or as prescriptions for levothyroxine. Two analytic models were used: (i) hypothyroidism present at the time of the breast cancer diagnosis (prevalent) and (ii) hypothyroidism diagnosed during follow-up as a time-varying exposure lagged by 1 year (incident). Breast cancer recurrence was defined as any local, regional, or distant recurrence or contralateral breast cancer. All-cause mortality included death from any cause in any setting. We used Cox regression models accounting for competing risks to compute adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer recurrence and all-cause mortality., Results: The study cohort included 35,463 women with breast cancer with 212,641 person-years of follow-up. At diagnosis, 1272 women had hypothyroidism and 859 women developed hypothyroidism during follow-up. In total, 5810 patients developed recurrent breast cancer. Neither prevalent nor incident hypothyroidism was associated with breast cancer recurrence (adjusted HR prevalent 1.01, 95% CI 0.87-1.19; adjusted HR incident 0.93, 95% CI 0.75-1.16, respectively). Furthermore, no differences were seen for all-cause mortality for prevalent or incident hypothyroidism (adjusted HR prevalent 1.02, 95% CI 0.92-1.14, and HR incident 1.08, 95% CI 0.95-1.23, respectively). Stratification by menopausal status, oestrogen receptor status, chemotherapy, or radiotherapy did not alter the estimates., Conclusions: Hypothyroidism present at diagnosis or during follow-up was not associated with breast cancer recurrence or all-cause mortality in women with breast cancer. Our findings provide reassurance to patients and their physicians that hypothyroidism is unlikely to impact on the clinical course of breast cancer or survival.

Pronounced fatigue including tiredness and lack of energy are common both during and after cancer treatment. Between 15–35 % of adult cancer survivors experience chronic fatigue. Chronic fatigue has a negative impact on affected individuals’ social, occupational and general functioning, and may lead to a considerably reduced quality of life.

Context: Chronic fatigue (CF) in breast cancer (BC) survivors is multifactorial and may be caused by immune activation triggered by BC or its treatment. In the Neoadjuvant Avastin in Breast Cancer study, BC patients received neoadjuvant chemotherapy (FEC100→taxane) ± bevacizumab, a monoclonal antibody with fatigue as a potential side effect., Objectives: To examine fatigue levels and prevalence of CF before and during chemotherapy and at follow-up, and their associations with C-reactive protein (CRP) and clinical variables., Methods: Eighty-four HER2-negative patients with cT2-4N0-3M0 BC responded to questionnaires and had CRP measured before treatment (T0), after FEC100 (T1), after taxanes before surgery (T2), and at two-year follow-up (T3)., Results: The prevalence of CF increased from 8% at T0 to 36% at T3, P < 0.0001. Fatigue levels peaked during chemotherapy from 12.0 at T0 to 20.0 at T2, and declined to 16.7 at T3, P < 0.001. Women with CF at T3 had higher fatigue levels at T0, T2, and T3 than those without CF (P ≤ 0.01). Psychological distress (P = 0.03) and pain (P = 0.04) at T3 were associated with CF at T3. Only psychological distress remained a significant predictor in multivariate analysis. CRP increased from T0 to T1 (P < 0.01) and declined to baseline values at T3, but changes were not associated with bevacizumab treatment. No association was found between bevacizumab or CRP, and fatigue levels or CF., Conclusion: Neither bevacizumab treatment nor low-grade systemic inflammation as measured by CRP was associated with the increased fatigue levels and raised prevalence of CF, observed during and after BC therapy. Increased fatigue levels at baseline and psychological distress at T3 were associated with CF at T3., (Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

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.

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.