| 1. |
- Nordenskjöld, Bo, 1940-, et al.
(författare)
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Coronary heart disease mortality after 5 years of adjuvant tamoxifen therapy: results from a randomized trial
- 2005
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Ingår i: J Natl Cancer Inst. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 97:21, s. 1609-10
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Tidskriftsartikel (refereegranskat)abstract
- From January 1, 1983, through December 31, 1992, a total of 4610 patients entered a randomized trial that compared mortality among patients receiving 2 years of adjuvant tamoxifen therapy with that in patients receiving 5 years of adjuvant tamoxifen therapy, 4175 of whom were recurrence free after 2 years of tamoxifen therapy. Among the 2046 patients randomly assigned to the 5-year group all-cause mortality, breast cancer-specific mortality, and the incidence of contralateral breast cancer were reduced, compared with those among 2129 patients randomized in the 2-year group, but the incidence of endometrial cancer was increased. In addition, mortality from coronary heart disease was statistically significantly reduced in the 5-year group, compared with that in the 2-year group (hazard ratio = 0.67, 95% confidence interval = 0.47 to 0.94; P = .022 [two-sided Wald test]). Ten years after surgery, 2.1% of the patients in the 5-year group and 3.5% of those in the 2-year group had died from coronary heart disease. No statistically significant increases in mortality from other heart diseases, cerebrovascular diseases, or other vascular diseases were observed.
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| 2. |
- Ahlberg, Karin, 1965, et al.
(författare)
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Fatigue, psychological distress, coping and quality of life in patients with uterine cancer.
- 2004
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Ingår i: Journal of advanced nursing. - 0309-2402. ; 45:2, s. 205-13
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cancer-related fatigue (CRF) is a subjectively experienced symptom that is multidimensional and multifactorial. Patients with cancer have identified fatigue as one of the major troubling symptoms and the primary cause of distress in their lives. AIMS: The major aim of the study was to examine how patients diagnosed with uterine cancer describe their experience of fatigue, psychological distress, coping resources and quality of life. A secondary aim was to describe the relationship between selected variables. METHOD: A descriptive and correlational design was used and the study was conducted at a university hospital in Sweden. The study population consisted of women, diagnosed with uterine cancer, who where scheduled to receive curative external radiation therapy. Sixty women participated in the study and data were collected through self-report instruments. Demographic and clinical data were extracted from patient records. The data were collected during year 2000-2002. The Conceptual Model of Symptom Management was used as a framework to guide the study. FINDINGS: Patients experienced a low grade of fatigue and psychological distress, but their functional status and global quality of life was high. Significant correlations were found between general fatigue and anxiety and also between general fatigue and depression. There was a significant negative correlation between general fatigue and coping resources. Depression explained 44% of the variance in general fatigue. CONCLUSIONS: The findings provide knowledge about predictors of CRF in women with uterine cancer, and can serve as a basis for future longitudinal studies in which different prophylactic strategies against therapy-related fatigue are prospectively studied.
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| 3. |
- Bergman, Annika, et al.
(författare)
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Genome-wide linkage scan for breast cancer susceptibility loci in Swedish hereditary non-BRCA1/2 families : Suggestive linkage to 10q23.32-q25.3
- 2007
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Ingår i: Genes, Chromosomes and Cancer. - : John Wiley & Sons. - 1045-2257 .- 1098-2264. ; 46:3, s. 302-309
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Tidskriftsartikel (refereegranskat)abstract
- The two breast cancer genes BRCA1 and BRCA2 were identified more than 10 years ago and, depending on population, mutations in these genes are responsible for a varying percentage of familial breast cancer. In more than half the families, the increased risk of breast cancer cannot be explained by mutations in these genes, and the goal of this study was to locate novel susceptibility genes. One of the main difficulties in identifying the cause of hereditary non-BRCA1/BRCA2 breast cancer is genetic heterogeneity, possibly due to multiple, incompletely penetrant susceptibility genes, along with ethnic and geographic differences. In this study, one large family and 13 small to medium-sized families with multiple cases of breast cancer were analyzed by genome-wide linkage analysis. The genome scan was performed by genotype analysis of 10,000 SNP markers on microarrays. The strongest evidence of linkage (HLOD 2.34) was obtained on chromosome region 10q23.32-q25.3. A further two regions were identified, with LOD scores above 2.10 on 12q14-q21 and 19p13.3-q12. In a subset of families of western Swedish origin, two regions generated LOD scores exceeding 1.8: 10q23.32-q25.3 and 19q13.12-q13.32. The large family in the study exceeded LOD 1.5 in three regions: 10q23.32-q25.3, 19q13.12-q13.32, and 17p13. Our results indicate that one or more of the suggested regions may harbor genes that are involved in the development of breast cancer.
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| 4. |
- Bergman, Annika, et al.
(författare)
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The western Swedish BRCA1 founder mutation 3171ins5; a 3.7 cM conserved haplotype of today is a reminiscence of a 1500-year-old mutation
- 2001
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Ingår i: European Journal of Human Genetics. - : Nature Publishing Group. - 1018-4813 .- 1476-5438. ; 9:10, s. 787-793
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Tidskriftsartikel (refereegranskat)abstract
- The most recurrent BRCA1/BRCA2 mutation in Sweden is the BRCA1 mutation 3171ins5. In the western part of Sweden this mutation accounts for as much as 77% of identified mutations in these two genes. Our aim was to analyse in detail the haplotype and founder effects of the 3171ins5 and furthermore attempt to estimate the time of origin of the mutation. In the study we included eighteen apparently unrelated families with hereditary breast and/or ovarian cancer. At least one individual in each family had previously tested positive for the 3171ins5 mutation. Polymorphic microsatellite markers were used for the haplotype analyses. The markers were located within or flanking the BRCA1 gene spanning a region of 17.3 cΜ. We found several different haplotypes both for disease alleles and for the normal alleles. However, a conserved haplotype of 3.7 cΜ was observed in the 3171ins5 carriers spanning over four markers located within or very close to the BRCA1 gene. As this haplotype was not present in any of the normal controls it is highly likely that this is a mutation identical by descent, i.e. a true founder. The results from the haplotype analyses were used to estimate the age of the mutation. Estimations based on the Pexcess and linkage disequilibrium gives a first appearance of the mutation sometime around the 6th century, approximately 50 generations ago.
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| 5. |
- Einbeigi, Zakaria, 1962, et al.
(författare)
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Clustering of individuals with both breast and ovarian cancer--a possible indicator of BRCA founder mutations.
- 2002
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Ingår i: Acta oncologica (Stockholm, Sweden). - 0284-186X. ; 41:2, s. 153-7
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Tidskriftsartikel (refereegranskat)abstract
- In a cohort of 60436 women with a diagnosis of invasive breast carcinoma and known to reside in Sweden in 1960, 321 had a subsequent diagnosis of ovarian carcinoma. Assuming no correlation between the two cancers, one would expect that 191 women would develop ovarian cancer (standardized incidence ratio (SIR) 1.7; 95% confidence interval 1.5-1.9). Women with breast cancer before 40 years of age were at highest risk for developing ovarian cancer (SIR 4.5). Between 40 and 49 years of age, the SIR was 1.9, and at 50 years of age or older, the SIR was 1.3. Most of the excess in ovarian cancer occurred in southern Sweden. The geographic distribution of these cases coincided with the distribution of families with known BRCA1 and BRCA2 gene mutations. These results suggest that genetic factors account for the excess in ovarian cancer that occurs in breast cancer patients and that geographic clustering of patients who have both breast and ovarian cancer may indicate the presence of a BRCA founder mutation.
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| 6. |
- Einbeigi, Zakaria, 1962, et al.
(författare)
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Occurrence of both breast and ovarian cancer in a woman is a marker for the BRCA gene mutations: a population-based study from western Sweden.
- 2007
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Ingår i: Familial cancer. - : Springer Science and Business Media LLC. - 1389-9600 .- 1573-7292. ; 6:1, s. 35-41
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Tidskriftsartikel (refereegranskat)abstract
- AIM: This study aimed to analyze whether the occurrence of both breast and ovarian cancer in a woman serves as a marker for BRCA gene mutations. MATERIAL AND METHODS: This population-based study included 256 women in western Sweden who developed both invasive breast and ovarian tumors between 1958 and 1999. Archival paraffin tissue blocks of their tumors were retrieved for DNA-extraction to analyze the founder mutation, BRCA1 c.3171_3175dup (c.3171ins5), which is most common in this geographic area and four other common Scandinavian BRCA1 gene mutations and one BRCA2 mutation. Together, account these mutations for approximately 75% of the BRCA1/2 gene mutations in the clinical unit. RESULTS: Ninteen percent (95% confidence interval (CI) 14-24%) of the women carried one of the analyzed BRCA1 gene mutations but none of the women were positive for the analyzed BRCA2 mutation. One-third of the women with both tumors before age 60 were mutation carriers. BRCA1 c.3171_3175dup (c.3171ins5) constituted 84% of all identified mutations. Although the majority of breast cancers were invasive ductal and atypical medullary types, a variety of other breast malignancies were seen among mutation carriers. Serous ovarian carcinomas predominated among ovarian tumors. A variety of other ovarian tumors, including three granulosa-theca cell tumors, were also observed among mutation carriers. CONCLUSIONS: The occurrence of both breast and ovarian cancer in a woman is associated with a high likelihood of a constitutional BRCA1 mutation. These women and their families might therefore be considered for mutation screening after appropriate genetic counselling.
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| 7. |
- Emdin, Stefan, et al.
(författare)
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SweDCIS: Radiotherapy after sector resection for ductal carcinoma in situ of the breast. Results of a randomised trial in a population offered mammography screening.
- 2006
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Ingår i: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 45:5, s. 536-43
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Tidskriftsartikel (refereegranskat)abstract
- We studied the effect of postoperative radiotherapy (RT) after breast sector resection for ductal carcinoma in situ (DCIS). The study protocol stipulated radical surgery but microscopically clear margins were not mandatory. We randomised 1,046 operated women to postoperative RT or control between 1987 and 1999. The primary endpoint was ipsilateral local recurrence. Secondary endpoints were contralateral breast cancer, distant metastasis and death. After a median follow-up of 5.2 years (range 0.1-13.8) there were 44 recurrences in the RT group corresponding to a cumulative incidence of 0.07 (95% confidence interval (CI) 0.05-0.10). In the control group there were 117 recurrences giving a cumulative incidence of 0.22 (95% CI 0.18-0.26) giving an overall hazard ratio of 0.33 (95% CI 0.24-0.47, p < 0.0001). Twenty two percent of the patients had microscopically unknown or involved margins. We found no evidence for different effects of RT on the relative risk of invasive or in situ recurrence. Secondary endpoints did not differ. Women undergoing sector resection for DCIS under conditions of population based screening mammography benefit from postoperative RT to the breast. Seven patients needed RT-treatment to prevent one recurrence.
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| 8. |
- Giobbie-Hurder, Anita, et al.
(författare)
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Design, conduct, and analyses of Breast International Group (BIG) 1-98: a randomized, double-blind, phase-III study comparing letrozole and tamoxifen as adjuvant endocrine therapy for postmenopausal women with receptor-positive, early breast cancer.
- 2009
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Ingår i: Clinical trials (London, England). - : SAGE Publications. - 1740-7745 .- 1740-7753. ; 6:3, s. 272-87
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Aromatase inhibitors provide superior disease control when compared with tamoxifen as adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer. PURPOSE: To present the design, history, and analytic challenges of the Breast International Group (BIG) 1-98 trial: an international, multicenter, randomized, double-blind, phase-III study comparing the aromatase inhibitor letrozole with tamoxifen in this clinical setting. METHODS: From 1998-2003, BIG 1-98 enrolled 8028 women to receive monotherapy with either tamoxifen or letrozole for 5 years, or sequential therapy of 2 years of one agent followed by 3 years of the other. Randomization to one of four treatment groups permitted two complementary analyses to be conducted several years apart. The first, reported in 2005, provided a head-to-head comparison of letrozole versus tamoxifen. Statistical power was increased by an enriched design, which included patients who were assigned sequential treatments until the time of the treatment switch. The second, reported in late 2008, used a conditional landmark approach to test the hypothesis that switching endocrine agents at approximately 2 years from randomization for patients who are disease-free is superior to continuing with the original agent. RESULTS: The 2005 analysis showed the superiority of letrozole compared with tamoxifen. The patients who were assigned tamoxifen alone were unblinded and offered the opportunity to switch to letrozole. Results from other trials increased the clinical relevance about whether or not to start treatment with letrozole or tamoxifen, and analysis plans were expanded to evaluate sequential versus single-agent strategies from randomization. LIMITATIONS: Due to the unblinding of patients assigned tamoxifen alone, analysis of updated data will require ascertainment of the influence of selective crossover from tamoxifen to letrozole. CONCLUSIONS: BIG 1-98 is an example of an enriched design, involving complementary analyses addressing different questions several years apart, and subject to evolving analytic plans influenced by new data that emerge over time.
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| 9. |
- Glimelius, Bengt, et al.
(författare)
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A systematic overview of radiation therapy effects in rectal cancer.
- 2003
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Ingår i: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 42, s. 476-
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Tidskriftsartikel (refereegranskat)abstract
- A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for rectal cancer is based on data from 42 randomized trials and 3 meta-analyses. Moreover, data from 36 prospective studies, 7 retrospective studies and 17 other articles were used. A total of 131 scientific articles are included, involving 25 351 patients. The results were compared with those of a similar overview from 1996 including 15 042 patients. The conclusions reached can be summarized thus: The results after rectal cancer surgery have improved during the past decade. It is likely that local failure rates after 5 years of follow-up at hospitals adopting the TME-concept (TME = total mesorectal excision) have decreased from about 28% to 10-15%. Preoperative radiotherapy at biological effective doses above 30 Gy decreases the relative risk of a local failure by more than half (50-70%). Postoperative radiotherapy decreases the risk by 30-40% at doses that generally are higher than those used preoperatively. There is strong evidence that preoperative radiotherapy is more effective than postoperative. There is moderate evidence that preoperative radiotherapy significantly decreases the local failure rate (from 8% to 2% after 2 years) also with TME. There is strong evidence that preoperative radiotherapy improves survival (by about 10%). There is no evidence that postoperative radiotherapy improves survival. There is some indication that survival is prolonged when postoperative radiotherapy is combined with concomitant chemotherapy. Preoperative radiotherapy at adequate doses can be given with low acute toxicity. Higher, and unacceptable acute toxicity has been seen in some preoperative radiotherapy trials using suboptimal techniques. Postoperative radiotherapy can also be given with acceptable acute toxicity. The long-term consequences of radiotherapy appear to be limited with adequate radiation techniques, although they have been less extensively studied. Longer follow-up periods are needed before firm conclusions can be drawn. Peroperative radiotherapy, preferably preoperative since it is more effective, is routinely recommended for most patients with rectal cancer since it can substantially decrease the risk of a local failure and increases survival. In a primarily non-resectable tumour, preoperative radiotherapy can cause tumour regression allowing subsequent radical surgery. This therapy is routinely indicated. Whether radiochemotherapy is more efficient than radiotherapy alone is not clear, since the results of four small randomized trials are partly conflicting. Preoperative radiotherapy, frequently combined with chemotherapy, has been used to increase the chances of sphincter-preserving surgery in low-lying tumours. The literature is inconclusive with respect to how frequently this occurs. Radiotherapy frequently produces symptom relief in patients with rectal cancer not amendable to surgery.
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| 10. |
- Holmberg, Erik, 1951, et al.
(författare)
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Dose-response relationship for parathyroid adenoma after exposure to ionizing radiation in infancy.
- 2002
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Ingår i: Radiation research. - 0033-7587. ; 158:4, s. 418-23
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Tidskriftsartikel (refereegranskat)abstract
- Several authors have suggested that there is an excess risk of hyperparathyroidism, adenomas or hyperplasia after exposure to ionizing radiation. There is still, however, some uncertainty about this association, because these diseases are often asymptomatic and escape clinical detection if not specially searched for. This study is based on a pooled Swedish cohort of 27,925 persons with skin hemangiomas. The majority received radiation treatment in infancy between 1920 and 1965 in Stockholm and Gothenburg. The mean age at treatment was 6 months and the median thyroid dose was 0.20 Gy (range 0-28.5 Gy). Record linkage with the Swedish Cancer Register for the period 1958-1997 gave 43 cases of parathyroid adenoma in the cohort. Analyses of excess relative risk (ERR) models were performed using Poisson regression methods. Clinical records were scrutinized to determine if the childhood radiation exposure was known (biased cases) at the time of diagnosis. Seven of the cases of parathyroid adenoma were classified as biased cases. The standardized incidence ratio (SIR) was 2.10 (95% confidence interval 1.52-2.82) when all cases were included and 1.76 (95% CI 1.23-2.43) with the biased cases excluded. A linear dose-response model with stratification for sex fitted the data best. The ERR per gray was 3.84 (95% CI 1.56-8.99) with all cases and 1.56 (95% CI 0.36-4.45) with the biased cases excluded. There was a significant difference in the ERR per gray between the two subcohorts, probably because of different diagnostic activity in the regions. Our findings confirm that there is a dose-response relationship for radiation-induced parathyroid adenomas.
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