1. |
- Altena, Renske, et al.
(author)
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Evidence-based prediction and prevention of cardiovascular morbidity in adults treated for cancer
- 2021
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In: Cardio-Oncology. - : BMC. - 2057-3804. ; 7:1
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Research review (peer-reviewed)abstract
- Background Cancer treatment-related morbidity relevantly compromises health status in cancer survivors, and efforts to optimise health-related outcomes in this population are vital to maximising healthy survivorship. A pre-treatment assessment - and possibly preventive management strategies - of cancer patients at increased risk for cardiovascular disease (CVD) seems a rational approach in this regard. Definitive evidence for such strategies is largely lacking, thereby impeding the formulation of firm recommendations. Results The current scoping review aims to summarise and grade the evidence regarding strategies for prediction and prevention of CVD in adults in relation to oncological treatments. We conducted a scoping literature search for different strategies for primary prevention, such as medical and lifestyle interventions, as well as the use of predictive risk scores. We identified studies with moderate to good strength and up to now limited evidence to recommend primary preventive strategies in unselected patients treated with potentially cardiotoxic oncologic therapies. Conclusion Efforts to minimize the CVD burden in cancer survivors are needed to accomplish healthy survivorship. This can be done by means of robust models predictive for CVD events or application of interventions during or after oncological treatments. Up to now there is insufficient evidence to implement preventive strategies in an unselected group of patients treated with potential cardiotoxic oncological treatments. We conclude that randomised controlled trials are needed that evaluate medical and lifestyle interventions in groups at increased risk for complications, in order to be able to influence chronic illness risks, such as cardiovascular complications, for cancer survivors.
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2. |
- Brand, Judith S, et al.
(author)
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Chemotherapy, genetic susceptibility, and risk of venous thromboembolism in breast cancer patients
- 2016
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In: Clinical Cancer Research. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1078-0432. ; 22:21, s. 5249-5255
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Journal article (peer-reviewed)abstract
- Purpose: Venous thromboembolism (VTE) is highly heritable and a serious complication of cancer and its treatment. We examined the individual and joint effects of chemotherapy and genetic susceptibility on VTE risk in patients with breast cancer. Experimental design: A Swedish population-based study including 4,261 women diagnosed with primary invasive breast cancer between 2001 and 2008 in Stockholm, followed until 2012. Risk stratification by chemotherapy and genetic susceptibility [a polygenic risk score (PRS), including nine established VTE loci] was assessed using Kaplan-Meier and flexible parametric survival analyses, adjusting for patient, tumor, and treatment characteristics. Results: In total, 276 patients experienced a VTE event during a median follow-up of 7.6 years. Patients receiving chemotherapy [HR (95% CI) = 1.98; 1.40-2.80] and patients in the highest 5% of the PRS [HR (95% CI) = 1.90; 1.24-2.91] were at increased risk of developing VTE. Chemotherapy and PRS acted independently on VTE risk and the 1-year cumulative incidence in patients carrying both risk factors was 9.5% compared with 1.3% in patients not having these risk factors (P < 0.001). Stratified analyses by age showed that the risk-increasing effect of PRS was stronger in older patients (P interaction = 0.04), resulting in an excess risk among genetically susceptible patients receiving chemotherapy aged ≥ 60 years (1-year cumulative incidence = 25.0%). Conclusions: Risk stratification by chemotherapy and genetic susceptibility identifies patients with breast cancer at high VTE risk, who could potentially benefit from thromboprophylaxis. Our results further suggest that genetic testing is more informative in older patients with breast cancer.
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3. |
- Brand, Judith S, et al.
(author)
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Time-dependent risk and predictors of venous thromboembolism in breast cancer patients: a population-based cohort study
- 2016
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In: Cancer. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0008-543X .- 1097-0142.
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Journal article (peer-reviewed)abstract
- BACKGROUND: Venous thromboembolism (VTE) is a serious complication of cancer and its treatment. The current study assessed the risk and clinical predictors of VTE in breast cancer patients by time since diagnosis. METHODS: This Swedish population-based study included 8338 breast cancer patients diagnosed from 2001 to 2008 in the Stockholm-Gotland region with complete follow-up until 2012. Their incidence of VTE was compared with the incidence among 39,013 age-matched reference individuals from the general population. Cox and flexible parametric models were used to examine associations with patient, tumor, and treatment characteristics, accounting for time-dependent effects. RESULTS: Over a median follow-up of 7.2 years, 426 breast cancer patients experienced a VTE event (cumulative incidence, 5.1%). The VTE incidence was 3-fold increased (hazard ratio [HR], 3.28; 95% confidence interval [CI], 2.87-3.74) in comparison with the incidence in the general population and was highest 6 months after diagnosis (HR, 8.62; 95% CI, 6.56-11.33) with a sustained increase in risk thereafter (HR at 5 years, 2.19; 95% CI, 1.80-2.67). Independent predictors of VTE included the following: older age, being overweight, preexisting VTE, comorbid disease, tumor size > 40 mm, progesterone receptor (PR)-negative status, more than 4 affected lymph nodes, and receipt of chemo- and endocrine therapy. The impact of chemotherapy was limited to early-onset VTE, whereas comorbid disease and PR-negative status were more strongly associated with late-onset events. CONCLUSIONS: This study confirms the long-term risk of VTE in breast cancer patients and identifies a comprehensive set of clinical risk predictors. Temporal associations with patient, tumor, and treatment characteristics provide insight into the time-dependent etiology of VTE.
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4. |
- Garvin, Stina, et al.
(author)
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Differences in intra-tumoral macrophage infiltration and radiotherapy response among intrinsic subtypes in pT1-T2 breast cancers treated with breast-conserving surgery
- 2019
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In: Virchows Archiv. - : SPRINGER. - 0945-6317 .- 1432-2307. ; 475:2, s. 151-162
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Journal article (peer-reviewed)abstract
- Breast cancer (BC) intrinsic subtype classification is based on the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and proliferation marker Ki-67. The expression of these markers depends on both the genetic background of the cancer cells and the surrounding tumor microenvironment. In this study, we explore macrophage traits in cancer cells and intra-tumoral M2-macrophage infiltration (MI) in relation to intrinsic subtypes in non-metastatic invasive BC treated with breast conserving surgery, with and without postoperative radiotherapy (RT). Immunostaining of M2-macrophage-specific antigen CD163 in cancer cells and MI were evaluated, together with ER, PR, HER2, and Ki-67-expression in cancer cells. The tumors were classified into intrinsic subtypes according to the ESMO guidelines. The immunostaining of these markers, MI, and clinical data were analyzed in relation to ipsilateral local recurrence (ILR) as well as recurrence-free (RFS) and disease-free specific (DFS) survival. BC intrinsic subtypes are associated with T-stage, Nottingham Histologic Grade (NHG), and MI. Macrophage phenotype in cancer cells is significantly associated with NHG3-tumors. Significant differences in macrophage infiltration were observed among the intrinsic subtypes of pT1-T2 stage BC. Shorter RFS was observed in luminal B HER2neg tumors after RT, suggesting that this phenotype may be more resistant to irradiation. Ki-67-expression was significantly higher in NHG3 and CD163-positive tumors, as well as those with moderate and high MI. Cancer cell ER expression is inversely related to MI and thus might affect the clinical staging and assessment of BC.
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5. |
- He, Wei, et al.
(author)
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Concomitant Discontinuation of Cardiovascular Therapy and Adjuvant Hormone Therapy Among Patients With Breast Cancer
- 2023
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In: JAMA Network Open. - : AMER MEDICAL ASSOC. - 2574-3805. ; 6:7
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Journal article (peer-reviewed)abstract
- IMPORTANCE A large proportion of patients with breast cancer concomitantly use adjuvant hormone therapy and cardiovascular therapy. OBJECTIVE To examine the relative risk of discontinuing cardiovascular therapy during the periods before and after discontinuation of adjuvant hormone therapy. DESIGN, SETTING, AND PARTICIPANTS This population-based cohort study included all women aged 40 to 74 years in Stockholm, Sweden, who were diagnosed with breast cancer and concomitantly using adjuvant hormone therapy and cardiovascular therapy. Patients were enrolled from July 1, 2005, to August 31, 2020, with a median follow-up of 7.2 years. Data were analyzed from November 3, 2021, to May 12, 2022. EXPOSURE Discontinuation of adjuvant hormone therapy. MAIN OUTCOMES AND MEASURES The main outcome was discontinuation of cardiovascular therapy (cardiovascular drugs, statins, or aspirin) within 1 year before and after discontinuation of adjuvant hormone therapy. Incidence rate ratios with 95% CIs were estimated using Poisson regression. Furthermore, hazard ratios (HRs) with 95% CIs for cause-specific mortality were estimated using Cox proportional hazards regression models, comparing those who discontinued and continued adjuvant hormone therapy. RESULTS A total of 5493 patients with breast cancer who concomitantly used cardiovascular therapy were identified; 1811 who discontinued adjuvant hormone therapy were individually matched to 1 patient each who continued therapy by year of breast cancer diagnosis, age at diagnosis, and use of the same cardiovascular therapy. Most patients (4070 [74.1%]) were aged 60 years or older at diagnosis. At the time when patients discontinued adjuvant hormone therapy, 248 (12.2%) concomitantly discontinued their cardiovascular therapy. During follow-up, a higher discontinuation rate of cardiovascular therapy was also observed among those who discontinued adjuvant hormone therapy. Consistently, adjuvant hormone therapy discontinuation was associated with an increased risk of death not only due to breast cancer (HR, 1.43; 95 CI%, 1.01-2.01) but also cardiovascular disease (HR, 1.79; 95 CI%, 1.15-2.81). Stratifying the analyses on baseline type of adjuvant hormone therapy yielded consistent results. CONCLUSIONS AND RELEVANCE In this cohort study of data from population-based registers in Sweden, patients who discontinued adjuvant hormone therapy were also more likely to discontinue cardiovascular therapy, especially at the time when they discontinued adjuvant hormone therapy. These findings suggest that clinicians should shift from single- to multiple-disease focus to prevent discontinuation of therapies for other diseases among patients with breast cancer.
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6. |
- Hedayati, Elham, et al.
(author)
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Cognitive, psychosocial, somatic and treatment factors predicting return to work after breast cancer treatment
- 2013
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In: Scandinavian Journal of Caring Sciences. - : Wiley-Blackwell. - 0283-9318 .- 1471-6712. ; 27:2, s. 380-387
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Journal article (peer-reviewed)abstract
- Scand J Caring Sci; 2013; 27; 380387 Cognitive, psychosocial, somatic and treatment factors predicting return to work after breast cancer treatment Background: Breast cancer (BC) may affect the ability to work. In this study, we want to identify any associations between cognitive, psychosocial, somatic and treatment factors with time to return to work (RTW) among women treated for BC. Methods and participants: At eight (baseline) and 11(follow-up) months after BC diagnosis, women who had received adjuvant treatment for early BC at Stockholm South General Hospital completed the Headminder neuropsychological tests to obtain the Cognitive Stability Index (CSI), the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire and its Breast Cancer Module. At both time points, we compared the scores from women who had returned to work with those who had not. We also reviewed the medical certificates of women still on sick leave at 8, 11 and 18months after diagnosis to determine why they had not returned to work. Results: At baseline, 29 of 45 enroled women were working and 15 were not (one dropped out after baseline testing). The 14 women still not working 11months after BC diagnosis had more advanced BC (OR=3.64, 95% CI 2.017.31), lymph-node involvement (OR=18.80, 95% CI 5.3290.69) and Her 2-positive tumours (OR=10.42,95% CI 2.1965.32) than did working women. None of the scores for the four cognitive domains changed significantly at follow-up in either group. Comments on the medical certificates generally supported these findings. Independently of any adjuvant cancer therapy, overall quality of life improved and most women did RTW 18months after BC diagnosis. Conclusions: Chemotherapy is associated with longer periods of sick leave. Cognitive functions do not predict RTW. Independently of any adjuvant therapy, most women eventually RTW in a few months. The ability to predict RTW after BC treatment should help prepare higher-risk patients for delayed RTW and allow earlier interventions to restore their social relations and quality of life.
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7. |
- Hedayati, Elham, et al.
(author)
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Effects of adjuvant treatment on cognitive function in women with early breast cancer
- 2012
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In: European Journal of Oncology Nursing. - : Elsevier. - 1462-3889 .- 1532-2122. ; 16:3, s. 315-322
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Journal article (peer-reviewed)abstract
- Purpose: Whether adjuvant therapy impairs cognitive function in women with breast cancer (BC) is unclear. We determined the effects of adjuvant therapy on cognitive function in women with early BC. Methods: We consecutively and prospectively enrolled women aged 40-69 years who had a positive radiographic finding from the mammography screening program at Stockholm South General Hospital. All women completed the Headminder Web-based neuropsychological battery Cognitive Stability Index (CSI) for response speed, processing speed, memory, and attention before diagnosis (T1), after surgery and before adjuvant treatment (T2), 6 months after start of adjuvant treatment (T3), and after another 3 months of follow-up (T4). Women with BC were divided into those receiving chemotherapy, hormone therapy, or no adjuvant medical therapy. Women without a diagnosis of BC served as healthy controls. Results: Of the 146 women enrolled, 77 had BC of whom 18 received chemotherapy; 45, hormone therapy, and 14, no adjuvant medical therapy; 69 were healthy controls. Memory scores for women with BC were significantly lower than those for controls over time, even after controlling for age and education. Memory and response speed scores were lower after chemotherapy than before (P less than 0.01 for both). Processing speed and attention improved significantly over time in all groups, a result consistent with a practice effect. Conclusion: Our results indicate subtle changes related to time course and treatment. Especially, that chemotherapy may impair memory and response speed in women with BC, consistent with those reported by BC survivors after adjuvant medical treatment. (C) 2011 Elsevier Ltd. All rights reserved.
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8. |
- Hedayati, Elham, et al.
(author)
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The effects of breast cancer diagnosis and surgery on cognitive functions
- 2011
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In: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 50:7, s. 1027-1036
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Journal article (peer-reviewed)abstract
- Background. Women with breast cancer (BC) report cognitive impairment. Receiving a BC diagnosis may have a negative psychological impact. We sought to determine whether a diagnosis of BC and subsequent surgical treatment reduced cognitive function. Material and methods. We recruited women, who had a positive radiographic finding, consecutively from the mammography screening program at Stockholm South General Hospital. All subjects completed the Headminder Web-based neuropsychological battery Cognitive Stability Index (CSI) for response speed, processing speed, memory, and attention at enrolment (T1, Baseline). CSI was administered again, after BC was ruled out, or after sector resection or mastectomy, if BC was confirmed by cytology or biopsy (T2, Retest). Results and conclusion. Of the 148 women approached, 146 were enrolled; 69 were healthy and 77 had BC. Comparison between groups at baseline, according to independent t-test, showed significant differences in response speed and processing speed. Cognitive abilities did not decline in either group on any of the measured domains. Our results suggest that a diagnosis of BC and subsequent surgery is not associated with substantial cognitive decline at retest. However, the lack of improvement in attention at retest among BC patients may be suggestive of a decline.
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9. |
- Hedayati, Elham
(author)
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The effects of breast cancer treatment on cognitive functions
- 2012
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Doctoral thesis (other academic/artistic)abstract
- Aims: Women with breast cancer have reported difficulties with memory, attention, and concentration during or after adjuvant treatment. Whether these symptoms are side effects of treatment has not been established. The aim of this project was to determine the effects of early-stage breast cancer (BC) diagnosis and treatment on cognitive functions, quality of life, and psychological wellbeing. A secondary aim was to identify any associations between cognitive, psychosocial, somatic, and treatment factors and time to return to work (RTW) among women treated for early-stage BC. Methods: From the mammography screening program at Stockholm South General Hospital, we prospectively enrolled women aged 40 to 69 years who had a positive radiographic finding. All women completed the Headminder Web-based neuropsychological battery Cognitive Stability Index for response speed, processing speed, memory, and attention before diagnosis (T1), after surgery but before adjuvant treatment (T2), 6 months after starting adjuvant treatment (T3), and after another 3 months of follow-up (T4). Women with BC were divided into those receiving chemotherapy, hormone therapy, or no adjuvant medical therapy. Women eventually determined not to have BC served as healthy controls. At each test session, depression, anxiety, and quality of life were measured using the Swedish version of the Beck Depression Inventory, the Beck Anxiety Inventory, and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire and its BC supplementary measure. The secondary aim was addressed by comparing the above-mentioned scores from BC women who had returned to work with those who had not, at both T3 and T4. We also reviewed the medical certificates of women still on sick leave at 8, 11, and 18 months after diagnosis to determine why they had not returned to work. Results and Conclusion: Of the 146 women enrolled, 77 had BC, of whom 18 received chemotherapy; 45, hormone therapy, and 14, no adjuvant medical therapy; 69 were healthy controls. At baseline, only response speed and processing speed differed significantly between groups. Our results suggest that a diagnosis of BC and subsequent surgery are not associated with substantial cognitive decline. However, the lack of improvement in attention at retest among BC patients may suggest a decline. Further, our results indicate subtle cognitive changes related to time and treatment. Chemotherapy may impair memory and response speed in women with BC, a finding consistent with those reported for BC survivors after adjuvant medical treatment. Breast cancer surgery and adjuvant treatment, irrespectively of type, reduces quality of life and psychological wellbeing, mostly related to time course. Global quality of life health status improved to baseline after 11 months from diagnosis. However, poor body image and lower subjective cognitive functions were sustained and should be addressed in long-term survivors of breast cancer to improve overall quality of life. Chemotherapy is associated with longer periods of sick leave. Cognitive functioning, objectively measured, does not predict RTW. Independently of any adjuvant therapy, most women eventually return to work in a few months. The ability to predict RTW after BC treatment should help prepare higher-risk women for delayed RTW and allow earlier interventions to restore their social relations and quality of life.
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10. |
- Hübbert, Laila, et al.
(author)
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Long-term and real-life incidence of cancer therapy-related cardiovascular toxicity in patients with breast cancer: a Swedish cohort study
- 2023
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In: Frontiers in Oncology. - : FRONTIERS MEDIA SA. - 2234-943X. ; 44
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Journal article (peer-reviewed)abstract
- BackgroundThe administration of anticancer drugs in females with comorbidity increases the risk for cancer therapy-related cardiovascular toxicity (CTR-CVT), which in turn contributes to cardiovascular disease (CVD). Furthermore, a pathophysiological connection between cancer and cardiovascular disease may exist. ObjectiveTo assess the long-term risks and predictors of CTR-CVT, including clinical hypertension (HT), coronary artery disease (CAD), heart failure (HF), atrial fibrillation (AF), as well as all-cause mortality in women diagnosed with early breast cancer (BC) and eligible for adjuvant chemotherapy in Sweden. MethodsData were extracted from Swedish registers and medical records on 433 women, 18-60 years of age, diagnosed 1998-2002 with lymph node-positive BC, and considered for adjuvant chemotherapy. CTR-CVT was defined as HT, CAD, HF, or AF after the diagnosis of BC. Follow-up was from the date of BC diagnosis until November 30, 2021, or death. Prevalence of CTR-CVT and all-cause mortality were calculated. Hazard ratios (HR) were determined for factors associated with CTR-CVT. ResultsThe median age was 50 (interquartile range (IQR) 32) years. 910 CTR-CVT events were diagnosed in 311 women with a median of 19.3 (IQR 15,3) years follow-up. The proportions of CTR-CVT events were: HT 281 (64%); CAD 198 (46%); HF 206 (47%); and AF 225 (51%). The cumulative incidence of CTR-CVT was 71.8%, and 50% of all 433 patients developed CTR-CVT within 11.7 years of BC diagnosis (standard deviation (SD) 0.57, 95% confidence interval (CI) 10.6-12.9). Age was a risk factor for CTR-CVT. Anthracycline increased the risk for HF (p=0,001; HR 2,0; 95%CI 1,4-2,8), CAD (p= 0,002; HR 1,7; 95% CI 1,2-2,4), and AF (p=0,013; HR 1,5; 95% CI 1,0-2,0). At the end of the 24-year study period, 227 of the 433 women were alive, and the total cumulative mortality was 47,6%. ConclusionThe prevalence of CTR-CVT and all-cause mortality is high after BC diagnosis and treatment, particularly in older patients and those receiving anthracyclines. These findings and the onset of CTR-CVT support cardio-oncology guidelines recommending initial risk stratification and cardiovascular monitoring during treatment, followed by long-term annual screening for cardiovascular risk factors and CTR-CVT among BC survivors.
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11. |
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12. |
- Hägglund, Hanna L., et al.
(author)
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Poorer survival after out-of-hospital cardiac arrest among cancer patients : a population-based register study
- 2023
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In: European Heart Journal: Acute Cardiovascular Care. - 2048-8726 .- 2048-8734. ; 12:8, s. 495-503
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Journal article (peer-reviewed)abstract
- Aims: The association between cancer and survival after out-of-hospital cardiac arrest (OHCA) has not been thoroughly investigated. We aimed to address this knowledge gap using national, population-based registries. Methods and results: For this study, 30 163 patients with OHCA (≥18 years) were included from the Swedish Register of Cardiopulmonary Resuscitation. Through linkage to the National Patient Registry, 2894 patients (10%) with cancer diagnosed within 5 years prior to OHCA were identified. Differences in 30-day survival between patients with cancer and controls (defined as patients with OHCA without previous cancer diagnosis) were assessed related to cancer stage (locoregional vs. metastasized cancer) and cancer site (e.g. lung cancer, breast cancer, etc.) using logistic regression adjusted for prognostic factors. Long-term survival was presented as a Kaplan-Meier curve. For locoregional cancer, no statistically significant difference in return of spontaneous circulation (ROSC) was seen compared with controls, and metastasized disease was associated with a poorer chance of ROSC. Cancer was associated with a lower 30-day survival for all cancers [adjusted odds ratio (OR) 0.57, confidence interval (CI) 0.49-0.66], locoregional cancer (adjusted OR 0.68, CI 0.57-0.82), and metastasized cancer (adjusted OR 0.24, CI 0.14-0.40) compared with controls. A lower 30-day survival compared with controls was seen for lung, gynaecological and haematological cancers. Conclusion: Cancer is associated with poorer 30-day survival after OHCA. This study suggests that cancer site and disease stage are more relevant factors than cancer in general with regard to its effect on survival after OHCA.
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13. |
- Oda, Husam, et al.
(author)
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GATA-3 expression in breast cancer is related to intratumoral M2 macrophage infiltration and tumor differentiation
- 2023
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:3
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Journal article (peer-reviewed)abstract
- Accumulating evidence indicates that tumor-associated macrophages promote tumor progression and that high macrophage infiltration is correlated with advanced tumor stages and poor prognosis in breast cancer. GATA binding protein 3 (GATA-3) is a differentiation marker related to differentiated states in breast cancer. In this study, we explore how the extent of MI relates to GATA-3 expression, hormonal status, and the differentiation grade of breast cancer. To examine breast cancer in early development, we selected 83 patients that were treated with radical breast-conserving surgery (R0), without lymph node metastases (N0) or distant metastases (M0), with and without postoperative radiotherapy. Immunostaining of M2-macrophage-specific antigen CD163 was used to detect tumor-associated macrophages, and macrophage infiltration was estimated semi-quantitatively into no/low, moderate, and high infiltration. The macrophage infiltration was compared to GATA-3, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 expression in cancer cells. GATA-3 expression is associated with ER and PR expression but inversely correlated to macrophage infiltration and Nottingham histologic grade. High macrophage infiltration in advanced tumor grade was associated with low GATA-3 expression. The disease-free survival is inversely related to Nottingham histologic grade in patients having tumors with no/low macrophage infiltration, a difference that is not found in patients with moderate/high macrophage infiltration. These findings indicate that macrophage infiltration might impact the differentiation, malignant behavior, and prognosis of breast cancer, regardless of the morphological and hormonal states of the cancer cells in the primary tumor.
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14. |
- Papakonstantinou, Antroula, et al.
(author)
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Efficacy and safety of tailored and dose-dense adjuvant chemotherapy and trastuzumab for resected HER2-positive breast cancer : Results from the phase 3 PANTHER trial
- 2020
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In: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 126:6, s. 1175-1182
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Journal article (peer-reviewed)abstract
- Background: Dose-dense (DD) adjuvant chemotherapy improves outcomes in early breast cancer (BC). However, there are no phase 3 randomized data to inform on its combination with trastuzumab for patients with human epidermal growth factor receptor 2 (HER2)–positive disease. Methods: This was a protocol-predefined secondary analysis of the randomized phase 3 Pan-European Tailored Chemotherapy (PANTHER) trial. Women 65 years old or younger with node-positive or high-risk, node-negative BC were randomized 1:1 to either tailored (according to hematologic nadirs) and DD epirubicin and cyclophosphamide followed by docetaxel or standard 5-fluorouracil, epirubicin, and cyclophosphamide plus docetaxel every 3 weeks. Patients with HER2-positive disease received 1 year of adjuvant trastuzumab. The primary endpoint was BC relapse–free survival. In addition, HER2-positive patients and an equal number of HER2-negative patients matched for age, treatment group, and institution who were enrolled at Swedish sites were asked to participate in a predefined study of cardiac safety and underwent echocardiography or multigated acquisition scanning and electrocardiography at the baseline and at 4 and 6 years of follow-up. Results: There were 342 HER2-positive patients; 335 received at least 1 dose of trastuzumab, and 29 patients discontinued trastuzumab prematurely. Relapse-free survival was not statistically significantly in favor of the tailored and DD group (hazard ratio, 0.68; 95% confidence interval, 0.37-1.27; P =.231). Cardiac outcomes after 4 and 6 years of follow-up did not differ significantly between HER2-positive and HER2-negative patients or between the 2 treatment groups. Conclusions: The combination of DD chemotherapy and trastuzumab decreased the relative risk for relapse by 32% in comparison with standard treatment, a statistically nonsignificant difference. Its efficacy and safety merit further evaluation as part of both escalation and de-escalation strategies.
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15. |
- Stenmarker, Margaretha, et al.
(author)
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Morbidity and mortality among children, adolescents, and young adults with cancer over six decades : a Swedish population-based cohort study (the Rebuc study)
- 2024
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In: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 42
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Journal article (peer-reviewed)abstract
- Background Despite progress in managing cancer in children, adolescents, and young adults (CAYAs), persistent complications may impact their quality of life. This study covers the morbidity and mortality, among CAYAs, with the aim to investigate the influence of socioeconomic factors on outcomes. Methods This retrospective matched cohort study included the entire Swedish population of individuals under 25 with cancer 1958 - 2021. The population was identified from the Cancer Register, and controls were paired 1:5 based on age, sex, and residence. Multiple registers provided data on morbidity, mortality, and demographics. Findings This survey covering 63 years, identified 65,173 CAYAs and matched controls, a total of 378,108 individuals (74% females). CAYAs exhibited a 3.04 -times higher risk for subsequent cancer (Odds ratio (OR) 95% confidence interval (CI) 2.92 - 3.17, p < 0.0001), a 1.23 -times higher risk for cardiovascular disease (OR 95% CI 1.20 - 1.26, p < 0.0001), and a 1.41 -times higher risk for external affliction (OR 95% CI 1.34 - 1.49, p < 0.0001). CAYAs had a higher mortality hazard, and after adjusting for socioeconomic factors, males, individuals born outside Europe, and those with greater sick -leave had a higher association with mortality, while education and marriage showed a beneficial association. Interpretation The Rebuc study, showed an increased risk for serious complications among young cancer patients in Sweden. Patient -specific variables, demographics, and socioeconomic factors influenced mortality. These results underscore the impact of cancer on the health and lifespan of young individuals and the necessity for further research to address socioeconomic disparities in cancer care.
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16. |
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17. |
- Sundbom, Per, et al.
(author)
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Young Woman With Breast Cancer and Cardiotoxicity With Severe Heart Failure Treated With a HeartMate II (TM) for Nearly 6 Years Before Heart Transplantation
- 2014
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In: ASAIO journal (1992). - : Lippincott, Williams andamp; Wilkins. - 1058-2916 .- 1538-943X. ; 60:6, s. E3-E4
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Journal article (peer-reviewed)abstract
- Cardiotoxicity is a multifactorial problem, which has emerged with the improvement of cancer therapies and survival. Heart transplantation is relatively contraindicated in patients with breast cancer, until at least 5 years after complete remission. We present a case where a young woman who in 2001, at the age of 31, was diagnosed with breast cancer. She was considered cured, but 4 years later she suffered a relapse. During her second treatment, in 2006, she suffered from severe heart failure. She received a HeartMate II, as a long-term bridge to transplantation and 6 years later she was successfully transplanted. In this case report we discuss the use of mechanical circulatory support in cancer patients with drug-induced heart failure.
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18. |
- Thurell, Jacob, et al.
(author)
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Risk-adjusted benchmarking of long-term overall survival in patients with HER2-positive early-stage Breast cancer : A Swedish retrospective cohort study
- 2023
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In: Breast. - 0960-9776. ; 70, s. 18-24
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Journal article (peer-reviewed)abstract
- Aim: The main objective of the current study was to explore the value of risk-adjustment when comparing (i.e. benchmarking) long-term overall survival (OS) in breast cancer (BC) between Swedish regions. We performed risk-adjusted benchmarking of 5- and 10-year OS after HER2-positive early BC diagnosis between Sweden's two largest healthcare regions, constituting approximately a third of the total population in Sweden. Methods: All patients diagnosed with HER2-positive early-stage BC between 01-01–2009 and 31-12-2016 in healthcare regions Stockholm-Gotland and Skane were included in the study. Cox proportional hazards model was used for risk-adjustment. Unadjusted (i.e. crude) and adjusted 5- and 10-year OS was benchmarked between the two regions. Results: The crude 5-year OS was 90.3% in the Stockholm-Gotland region and 87.8% in the Skane region. The crude 10-year OS was 81.7% in the Stockholm-Gotland region and 77.3% in the Skane region. However, when adjusted for age, menopausal status and tumour biology, there was no significant OS disparity between the regions, neither at the 5-year nor 10-year follow-up. Conclusion: This study showed that risk-adjustment is relevant when benchmarking OS in BC, even when comparing regions from the same country that share the same national treatment guidelines. This is, to our knowledge, the first published risk-adjusted benchmarking of OS in HER2-positive BC.
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19. |
- Yang, Haomin, et al.
(author)
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Risk of heart disease following treatment for breast cancer - results from a population-based cohort study
- 2022
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In: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 11
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Journal article (peer-reviewed)abstract
- Background: There is a rising concern about treatment-associated cardiotoxicities in breast cancer patients. This study aimed to determine the time- and treatment-specific incidence of arrhythmia, heart failure, and ischemic heart disease in women diagnosed with breast cancer.Methods: A register-based matched cohort study was conducted including 8015 breast cancer patients diagnosed from 2001 to 2008 in the Stockholm-Gotland region and followed up until 2017. Time-dependent risks of arrhythmia, heart failure, and ischemic heart disease in breast cancer patients were assessed using flexible parametric models as compared to matched controls from general population. Treatment-specific effects were estimated in breast cancer patients using Cox model.Results: Time-dependent analyses revealed long-term increased risks of arrhythmia and heart failure following breast cancer diagnosis. Hazard ratios (HRs) within the first year of diagnosis were 2.14 (95% CI = 1.63-2.81) for arrhythmia and 2.71 (95% CI = 1.70-4.33) for heart failure. HR more than 10 years following diagnosis was 1.42 (95% CI = 1.21-1.67) for arrhythmia and 1.28 (95% CI = 1.03-1.59) for heart failure. The risk for ischemic heart disease was significantly increased only during the first year after diagnosis (HR = 1.45, 95% CI = 1.03-2.04). Trastuzumab and anthracyclines were associated with increased risk of heart failure. Aromatase inhibitors, but not tamoxifen, were associated with risk of ischemic heart disease. No increased risk of heart disease was identified following locoregional radiotherapy.Conclusions: Administration of systemic adjuvant therapies appears to be associated with increased risks of heart disease. The risk estimates observed in this study may aid adjuvant therapy decision-making and patient counseling in oncology practices.
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