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| 3. |
- Hatschek, T, et al.
(author)
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Individually tailored treatment with epirubicin and paclitaxel with or without capecitabine as first-line chemotherapy in metastatic breast cancer: a randomized multicenter trial
- 2012
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In: Breast Cancer Research and Treatment. - New York, USA : Springer Verlag (Germany). - 0167-6806 .- 1573-7217. ; 131:3, s. 939-947
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Journal article (peer-reviewed)abstract
- Anthracyclines and taxanes are active cytotoxic drugs in the treatment of early metastatic breast cancer. It is yet unclear whether addition of capecitabine to the combination of these drugs improves the treatment outcome. Patients with advanced breast cancer were randomized to first-line chemotherapy with a combination of epirubicin (Farmorubicin(A (R))) and paclitaxel (Taxol(A (R))) alone (ET) or in combination with capecitabine (Xeloda(A (R)), TEX). Starting doses for ET were epirubicin 75 mg/m(2) plus paclitaxel 175 mg/m(2), and for TEX epirubicin 75 mg/m(2), paclitaxel 155 mg/m(2), and capecitabine 825 mg/m(2) BID for 14 days. Subsequently, doses were tailored related to side effects. Primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), time to treatment failure (TTF), objective response (OR), safety and quality of life (QoL). 287 patients were randomized, 143 to ET and 144 to TEX. Median PFS was 10.8 months for patients treated with ET, and 12.4 months for those treated with TEX (HR 0.84, 95% CI 0.65-1.07, P = 0.16); median OS was 26.0 months for women in the ET versus 29.7 months in the TEX arm (HR 0.84, 95% CI 0.63-1.11, P = 0.22). OR was achieved in 44.8% (ET) and 54.2% (TEX), respectively (chi(2) 3.66, P = 0.16). TTF was significantly longer for patients treated with TEX, 6.0 months, versus 5.2 months following ET (HR 0.73, 95% CI 0.58-0.93, P = 0.009). Severe hematological side effects related to epirubicin and paclitaxel were evenly distributed between the treatment arms, mucositis, diarrhea, and Hand-Foot syndrome were significantly more frequent in the TEX arm. Toxicity-adjusted treatment with ET and TEX showed similar efficacy in terms of PFS, OS, and OR. In this trial with limited power, the addition of capecitabine to epirubicin and paclitaxel as first-line treatment did not translate into clinically relevant improvement of the outcome.
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| 4. |
- Bjohle, J, et al.
(author)
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Serum thymidine kinase activity compared with CA 15-3 in locally advanced and metastatic breast cancer within a randomized trial
- 2013
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In: Breast Cancer Research and Treatment. - : Springer Verlag (Germany). - 0167-6806 .- 1573-7217. ; 139:3, s. 751-758
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Journal article (peer-reviewed)abstract
- The primary objective was to estimate serum thymidine kinase 1 (TK1) activity, reflecting total body cell proliferation rate including cancer cell proliferation, in women with loco regional inoperable or metastatic breast cancer participating in a prospective and randomized study. Secondary objectives were to analyze TK1 in relation to progression-free survival (PFS), overall survival (OS), therapy response and other tumour characteristics, including CA 15-3, widely used as a standard serum marker for disease progression. TK1 and CA 15-3 were analysed in 198 serum samples collected prospectively from women included in the randomized TEX trial between December 2002 and June 2007. TK1 activity was determined by the ELISA based DiviTum (TM) assay, and CA 15-3 analyses was generated with the electrochemiluminescence immunoassay Cobas Elecsys CA 15-3 II. High pre-treatment TK1 activity predicted shorter PFS (10 vs. 15 months p = 0.02) and OS (21 vs. 38 months, p andlt; 0.0001), respectively. After adjustment for age, metastatic site and study treatment TK1 showed a trend as predictor of PFS (p = 0.059) and was an independent prognostic factor for OS, (HR 1.81, 95 % confidence interval (CI) 1.26-2.61, p = 0.001). There was a trend of shortened OS for women with high CA 15-3 (p = 0.054) in univariate analysis, but not after adjustment for the above mentioned covariates. Both TK1 (p = 0.0011) and CA 15-3 (p = 0.0004) predicted response to treatment. There were statistically different distributions of TK1 and CA 15-3 in relation to the site of metastases. TK1 activity measured by DiviTum (TM) predicted therapy response, PFS and OS in loco regional inoperable or disseminated breast cancer. These results suggest that this factor is a useful serum marker. In the present material, a prognostic value of CA 15-3 could not be proven.
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- Sodergren, M, et al.
(author)
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Associations between health-enhancing physical activity and country of birth among women
- 2010
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In: Journal of physical activity & health. - : Human Kinetics. - 1543-3080 .- 1543-5474. ; 7:5, s. 613-621
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Journal article (peer-reviewed)abstract
- The purpose of this study was to examine the association between total self-reported health-enhancing physical activity and country of birth among women living in Sweden.Methods:Women (age 18 to 65 years) born in Sweden, Finland, Chile, and Iraq were recruited for this cross-sectional study. Data were collected by means of a postal questionnaire including the International Physical Activity Questionnaire (IPAQ-long version). Self-reported physical activity data were converted to MET-minutes per week and analyzed as continuous or categorical scores. A total of 2649 women were included in the analyses. The association between physical activity and country of birth was explored using ordinal logistic regression assuming proportional odds.Results:The total physical activity differed significantly between the countries of birth (P < .001). Women from Finland had significant higher odds and women from Iraq had significantly lower odds for reporting higher levels of physical activity, compared with Swedish-born women.Conclusions:The direction of the associations between self-reported total health-enhancing physical activity varied by country of birth, which underlines the need to examine physical activity in each minority group separately.
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- Crump, C., et al.
(author)
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Sociodemographic, psychiatric and somatic risk factors for suicide: a Swedish national cohort study
- 2014
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In: Psychological Medicine. - 1469-8978. ; 44:2, s. 279-289
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Journal article (peer-reviewed)abstract
- Background More effective prevention of suicide requires a comprehensive understanding of sociodemographic, psychiatric and somatic risk factors. Previous studies have been limited by incomplete ascertainment of these factors. We conducted the first study of this issue using sociodemographic and out-patient and in-patient health data for a national population. Method We used data from a national cohort study of 7140589 Swedish adults followed for 8 years for suicide mortality (2001-2008). Sociodemographic factors were identified from national census data, and psychiatric and somatic disorders were identified from all out-patient and in-patient diagnoses nationwide. Results There were 8721 (0.12%) deaths from suicide during 2001-2008. All psychiatric disorders were strong risk factors for suicide among both women and men. Depression was the strongest risk factor, with a greater than 15-fold risk among women or men and even higher risks (up to 32-fold) within the first 3 months of diagnosis. Chronic obstructive pulmonary disease (COPD), cancer, spine disorders, asthma and stroke were significant risk factors among both women and men (1.4-2.1-fold risks) whereas diabetes and ischemic heart disease were modest risk factors only among men (1.2-1.4-fold risks). Sociodemographic risk factors included male sex, unmarried status or non-employment; and low education or income among men. Conclusions All psychiatric disorders, COPD, cancer, spine disorders, asthma, stroke, diabetes, ischemic heart disease and specific sociodemographic factors were independent risk factors for suicide during 8 years of follow-up. Effective prevention of suicide requires a multifaceted approach in both psychiatric and primary care settings, targeting mental disorders (especially depression), specific somatic disorders and indicators of social support.
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| 7. |
- Hemminki, Kari, et al.
(author)
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The epidemiology of Graves' disease: Evidence of a genetic and an environmental contribution.
- 2010
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In: Journal of Autoimmunity. - : Elsevier BV. - 0896-8411 .- 1095-9157. ; 34, s. 307-313
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Journal article (peer-reviewed)abstract
- Previous family and twin studies have indicated that Graves' disease has a heritable component. Family studies have also shown that some autoimmune disease cluster in families and genetic studies have been able to show shared susceptibility genes. In the present nation-wide study we describe familial risk for Graves' disease among parents and offspring, singleton siblings, twins and spouses with regard to age of onset, gender and number and type of affected family members. Additionally familial association of Graves' disease with any of 33 other autoimmune and related conditions was analyzed. The Swedish Multigeneration Register on 0-75-year-old subjects was linked to the Hospital Discharge Register from years 1987-2007. Standardized incidence ratios (SIRs) were calculated for individuals whose relatives were hospitalized for Graves' disease compared to those whose relatives were unaffected. The total number of hospitalized Graves' patients was 15,743. Offspring with an affected family member constituted 3.6% of all patients among offspring. The familial SIR was 5.04 for individuals whose sibling was affected but it increased to 310 when two or more siblings were affected; the SIR in twins was 16.45. Familial risks were higher for males than for females. The SIR was increased to 6.22 or 30.20 when parental age was limited to 50 or 20 years, respectively. Graves' disease associated with 19 other autoimmune and related conditions, including Addison's disease, type 1 diabetes mellitus, Hashimoto/hypothyroidism, pernicious anemia, polymyositis/dermatomyositis, myasthenia gravis, discoid lupus erythematosus and localized scleroderma. Remarkably, there was a high disease concordance of 2.75 between spouses. The clustering between spouses suggests environmental effects on Graves' disease which may contribute to the observed gender effects. The demonstrated high risks should be considered in clinical counseling and in prevention plans.
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| 8. |
- Fallah, M., et al.
(author)
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Hodgkin lymphoma after autoimmune diseases by age at diagnosis and histological subtype
- 2014
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In: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 25:7, s. 1397-1404
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Journal article (peer-reviewed)abstract
- Increased risk of Hodgkin lymphoma (HL) associated with personal history of several autoimmune diseases (ADs), such as rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, and immune thrombocytopenic purpura, are known. Whether there are other HL-related ADs and whether the increased risk of HL after ADs holds across sex, age, year of diagnosis, or HL histological subtype is unclear. We systematically analyzed the risk of HL in 878 161 Swedish patients diagnosed with 33 different ADs in 1964-2010. During similar to 10-year follow-up of ADs patients, 371 incident HL cases were diagnosed. Significantly increased overall standardized incidence ratio (SIR) for HL after ADs was 2.0 (95% confidence interval: 1.8-2.2); AD-specific SIRs: autoimmune hemolytic anemia 19.9 (7.2-43.6), sarcoidosis 10.3 (7.8-13.4), systemic lupus erythematosus 8.4 (5.2-12.9), immune thrombocytopenic purpura 7.0 (3.2-13.3), polyarteritis nodosa 6.6 (1.2-19.5), polymyositis/dermatomyositis 6.3 (2.0-14.9), Behcet's disease 5.6 (2.7-10.3), Sjogren's syndrome 5.0 (2.1-9.8), rheumatoid arthritis 3.2 (2.6-3.9), polymyalgia rheumatica 2.2 (1.4-3.5), and psoriasis 1.9 (1.3-2.6). Men with AD had slightly higher risk of HL (2.4, 2.0-2.7) compared with women (1.8, 1.5-2.0). Only 23% of ADs were diagnosed before age 35 years and the overall SIR for HL diagnosis before age 35 [1.4, (1.0-1.8)] was lower than that in older ages [35 a parts per thousand currency sign age < 50: 2.1 (1.6-2.7); age a parts per thousand yen 50: 2.2 (2.0-2.5)], except for sarcoidosis [age < 35: 19.3 (10.5-32.5); 35 a parts per thousand currency sign age < 50: 10.4 (5.7-17.5); age a parts per thousand yen 50: 8.4 (5.6-12.1)]. Risks of all classical HLs significantly increased after ADs: lymphocyte depletion 3.7 (1.5-7.6), lymphocyte-rich 3.7 (2.3-5.9), mixed cellularity 2.4 (1.8-3.2), and nodular sclerosis 1.7 (1.3-2.1). Several, but not all ADs (11/33), had a positive association with all classical histological subtypes of HL. Higher risks of classical HL after polyarteritis nodosa, polymyositis/dermatomyositis, Behcet's disease, Sjogren's syndrome, polymyalgia rheumatica, and psoriasis were novel findings of this study.
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| 9. |
- Hemminki, Kari, et al.
(author)
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Cancer of unknown primary (CUP): does cause of death and family history implicate hidden phenotypically changed primaries?
- 2012
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In: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 23:10, s. 2720-2724
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Journal article (peer-reviewed)abstract
- Cancer of unknown primary (CUP) is diagnosed at the metastatic stage. We aimed to identify hidden primary cancers in CUP patients by comparison with cancers in family members. We take use of the fact that the cause of death in CUP patients is often coded as the cancer in the organ of fatal metastasis. Forty-one thousand five hundred and twenty-three CUP patients were identified in the Swedish Family-Cancer Database, and relative risks (RRs) were calculated for cancer in offspring when family members were diagnosed with CUP and died of the cancer diagnosed in offspring. The RR for lung cancer in offspring was 1.85 when a family member was diagnosed with CUP and died of lung cancer. Significant familial associations were found for seven other cancers. Many familial associations were also significant when offspring CUP patients died of the cancer diagnosed in family members. The cause of death after CUP diagnosis frequently matched the cancer found in a family member, suggesting that the CUP had originated in that tissue. The metastasis had probably undergone a phenotypic change, complicating pathological tissue assignment. These novel data suggest that some CUP cases are phenotypically modified primary cancers rather than cancers of unknown primaries.
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| 10. |
- Hemminki, Kari, et al.
(author)
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Survival in cancer of unknown primary site: population-based analysis by site and histology
- 2012
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In: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 23:7, s. 1854-1863
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Journal article (peer-reviewed)abstract
- Cancer of unknown primary (CUP) is diagnosed at a metastatic stage, conferring an unfavorable prognosis. The natural history of the disease is poorly understood, which complicates diagnosis, treatment and follow-up. Population-based survival data are lacking regarding location and histology of metastases. From the Swedish Cancer Registry, 18 911 CUP patients were identified between years 1987 and 2008. Survival was analyzed by Kaplan-Meier survival curves and Cox regression. Adenocarcinoma accounted for 70% of all extranodal cases with a 12-month survival of 17% and the median survival of 3 months. Adenocarcinoma was also the most common histology (33.4%) when metastases were limited to lymph nodes, with a 12-month survival of 41% and median survival of 8 months. For extranodal metastases, the extremes in survival were small intestinal cancer with poor prognosis and mediastinal cancer with favorable prognosis. For nodal metastases, patients affected in the head and neck, axillary and inguinal regions had the best prognosis and those with abdominal and intrapelvic metastases the worst prognosis. The present data underline the importance of histology and location of metastasis in assisting clinical decision making: hazard ratios differed by a factor of five among extranodal and nodal metastases.
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| 11. |
- Riihimaeki, M., et al.
(author)
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Death causes in breast cancer patients
- 2012
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In: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 23:3, s. 604-604
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Journal article (peer-reviewed)abstract
- Background: Due to improved outcomes in breast cancer (BCa), the proportion of affected women dying of other causes has increased. Thus, a better survival of BCa requires knowledge of other causes of death. Materials and methods: Data on the population, cancers, and causes of death were gathered from the nationwide Swedish Family-Cancer Database, enrolling similar to 3.68 million Swedish women. A Cox regression model, comparing BCa patients against all other women, was applied. Cause-of-death-specific hazard ratios (HRs) were calculated for both underlying and multiple causes of death. Results: Among 641 000 deaths from 1987 to 2006, 48 000 were BCa patients. For underlying causes except BCa, the highest cause-specific HRs were found for diseases of pulmonary circulation {1.51 [95% confidence interval (CI) 1.36-1.68]}, suicide [1.39 (1.19-1.63)], and heart failure [1.29 (1.22-1.37)]. For specific multiple causes, the highest ratios were found for external causes [1.86 (1.80-1.91)] and gastrointestinal disease [1.68 (1.62-1.74)]. Conclusions: Diagnosis of BCa is associated with increased risks of dying of various causes, including external causes, heart failure, diseases of pulmonary circulation, and gastrointestinal disease. The study fulfills the gap in knowledge of death causes in BCa patients and suggests to draw more attention to comorbidities.
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