| 1. |
- Duffy, SW, et al.
(författare)
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The relative contributions of screen-detected in situ and invasive breast carcinomas in reducing mortality from the disease
- 2003
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Ingår i: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 39:12, s. 1755-1760
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to quantify the benefits of detecting ductal carcinoma in situ (DCIS) and of downwards stage-shifting within invasive tumours in mammographic screening. Using data from the Swedish Two-County Trial of breast cancer screening, we examined the 20-year death rates from invasive tumours of stage II or worse, invasive tumours of stage I and DCIS. We then used these rates and their respective incidences in invited (active study population, ASP) and control (passive study population, PSP) arms of the trial, to estimate the numbers of deaths avoided by downward stage-shifting the larger stage II or worse tumours to stage I and the stage I cancers to DCIS. We also studied the association between the mortality reduction achieved and the proportion of DCIS cases detected in the randomised trials of breast cancer screening. In the Swedish Two County Trial, 141 breast cancer deaths were avoided in the ASP compared with the PSP at approximately 20 years of follow-up. Of these, 65% (91/141) were avoided as a result of stage-shifting from invasive stage II or worse to invasive stage I, and 5% (7/141) as a result of stage-shifting from invasive stage I to DCIS. If we assumed that 10% of stage II or worse tumours avoided were shifted not to stage I, but to DCIS, the estimated number of deaths prevented by shifting from invasive disease to in situ was 17, which is 12% of all deaths prevented. When the results of all the randomised trials of breast cancer screening were reviewed, there was no clear association between the percentage of DCIS cases diagnosed and the observed mortality reduction. We conclude that compared with downward stage-shifting of invasive tumours, detection of DCIS plays a small part in saving lives from breast cancer. Treatment decisions in DCIS, as in invasive carcinoma, should take full account of histopathological, clinical and radiological attributes of the tumour. ⌐ 2003 Elsevier Ltd. All rights reserved.
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| 2. |
- Evertsson, Sofia, 1972-, et al.
(författare)
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APC I1307K and E1317Q variants are rare or do not occur in Swedish colorectal cancer patients
- 2001
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Ingår i: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 37:4, s. 499-502
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Tidskriftsartikel (refereegranskat)abstract
- Recently, a germ line mutation of the APC gene, I1307K, was discovered in a subset of Ashkenazi jews. The mutation involves an amino acid exchange and creates a tract consisting of eight contiguous adenosine residues believed to cause hypermutability in this region. Another germ line missense variant, E1317Q, not restricted to a certain ethnic population, could functionally alter the protein. These APC variants have been linked with increased colorectal cancer risk in several studies. However, they have not yet been investigated in Swedish colorectal cancer patients. Thus, our aim was to investigate the prevalence of I1307K and E1317Q in Swedish colorectal cancer patients in order to determine if these genetic variants are important predisposing factors to colorectal cancer in this population. To this end, sequence analysis was carried out of the APC gene in order to identify any I1307K and E1317Q variants in 106 unselected cases and 88 hereditary/familial colorectal cancer cases including 22 cases of hereditary non-polyposis colorectal cancer (HNPCC) fulfilling the Amsterdam criteria. Out of a total of 194 cases examined, we did not find any variants. It seems that these alterations are rare or absent in the Swedish population.
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| 3. |
- Fredriksson, I, et al.
(författare)
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Local recurrence in the breast after conservative surgery - A study of prognosis and prognostic factors in 391 women
- 2002
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Ingår i: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 38:14, s. 1860-1870
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Tidskriftsartikel (refereegranskat)abstract
- In a population-based cohort of 6613 women with invasive breast cancer, who had breast-conserving surgery between 1981 and 1990, 391 recurrences in the operated breast were identified. The main aim of this study was to examine the prognosis and prognostic factors in different subgroups of local recurrences, characterised by the time to recurrence, location of recurrence and previously given radiotherapy. The median follow-up for women who had a local recurrence was 7.9 years. The life-table estimates for breast cancer-specific survival in women with local recurrences were 84.5% (standard error (S.E.) 1.8) at 5 years and 70.9% (S.E. 2.7) at 10 years. The risk of breast cancer death was highest among women who had an early (=2 years) recurrence in the same quadrant as the primary tumour, with a breast cancer-specific survival of 67.9% (S.E. 4.8) at 5 years and 56.0% (S.E. 5.9) at 10 years. There was a statistically significant difference in the probability of breast cancer-specific survival, as measured from the recurrence, between women who initially did or did not receive radiotherapy (P=0.0123). However, when measured from primary treatment, there was no significant difference, indicating that the difference in prognosis could be due to a lead-time bias. Independent prognostic factors for breast cancer-specific survival in women with local recurrences were time to local recurrence and the Nottingham Prognostic Index (NPI). ⌐ 2002 Elsevier Science Ltd. All rights reserved.
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| 4. |
- Fredriksson, I, et al.
(författare)
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Time trends in the results of breast conservation in 4694 women
- 2001
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Ingår i: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 37:12, s. 1537-1544
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Tidskriftsartikel (refereegranskat)abstract
- In a population-based cohort of 4694 women with invasive breast cancer, operated upon with breast conserving surgery (BCS) in 1981-1990 and followed through to 1997, we studied how this technique had been adopted into clinical practice, especially with reference to the use of radiotherapy (RT). Our main aim was to see whether there was a drift in the risk of local recurrence and breast cancer death over time. During the 30 151 person-years of observation in the cohort, there were 582 local recurrences, 456 breast cancer deaths and 438 deaths due to other causes. Postoperative RT was given to 70.2%, but usage increased over the period. The women not receiving RT were mostly elderly, but also in women <70 years, 20.4% did not receive RT. The risk for local recurrence after RT were 7.6 and 17.8% at 5 and 10 years, respectively. Without RT, more than 30% had a local recurrence at 10 years. Thus, the choice not to irradiate failed to target women at a low risk. In a multivariate Cox analysis taking tumour size, nodal status, age at operation and RT into account, there was a trend for a higher risk of local recurrence in the later time period, relative hazard 1.5 (95% confidence interval (CI) 1.0-2.1). Corrected survival was 93.3 and 85.2% at 5 and 10 years, respectively. ⌐ 2001 Elsevier Science Ltd. All rights reserved.
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| 5. |
- Gentile, Massimiliano, et al.
(författare)
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p53 and survival in early onset breast cancer : analysis of gene mutations, loss of heterozygosity and protein accumulation
- 1999
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Ingår i: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 35:8, s. 1202-1207
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Tidskriftsartikel (refereegranskat)abstract
- The p53 protein has proven to be central in tumorigenesis by its cell cycle regulatory properties and both gene mutations and protein accumulation have been associated with poor prognosis in breast cancer. The present study was undertaken to investigate the prognostic significance of gene mutations, p53 protein accumulation and of loss of heterozygosity (LOH) at the TP53 locus in young (age <37 years) breast cancer patients. In total, gene mutations were found in 21 of the 123 patients (17%), LOH in 20 of the 47 informative cases (43%) and protein accumulation in 47 of the 102 available cases (46%). Log rank analysis revealed no significant association between survival and TP53 mutations (in general), p53 protein accumulation or LOH. However, missense mutations localised to the zinc binding domain were significantly (P=0.0007) associated with poorer prognosis. As indicated in this as well as other studies, p53 protein accumulation is frequently found in young breast cancer patients, but this protein overexpression appears to be of minor significance for survival. Nevertheless, the present report also suggests that specific mutations contribute substantially to tumour aggressiveness.
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| 6. |
- Marchand, M, et al.
(författare)
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Immunisation of metastatic cancer patients with MAGE-3 protein combined with adjuvant SBAS-2 : A clinical report
- 2003
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Ingår i: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 39:1, s. 70-77
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Tidskriftsartikel (refereegranskat)abstract
- Fifty-seven patients with MAGE-3-positive measurable metastatic cancer, most of them with melanoma, were vaccinated with escalating doses of a recombinant MAGE-3 protein combined with a fixed dose of the immunological adjuvant SBAS-2, which contained MPL and QS21. The immunisation schedule included 4 intramuscular (i.m.) injections at 3-week intervals. Patients whose tumour stabilised or regressed after 4 vaccinations received 2 additional vaccinations at 6-week intervals. The vaccine was generally well tolerated. Among the 33 melanoma patients who were evaluable for tumour response, we observed 2 partial responses, 2 mixed responses and 1 stabilisation. Time to progression in these 5 patients varied from 4 to 29 months. In addition, a partial response lasting 10 months was observed in 1 of the 3 metastatic bladder cancer patients included. None of the tumour responses described above involved visceral metastases. Immunological responses to the vaccine will be reported separately. ⌐ 2002 Elsevier Science Ltd. All rights reserved.
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| 7. |
- Morales, MM, et al.
(författare)
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Viral infection, atopy and mycosis fungoides : A European multicentre case-control study
- 2003
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Ingår i: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 39:4, s. 511-516
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Tidskriftsartikel (refereegranskat)abstract
- Mycosis fungoides (MF) is a rare disease with an unknown aetiology, although it has been suggested that infections may play a role. The present study investigates whether infections, atopic disorders and some other diseases are risk indicators for MF. A European multicentre case-control study involving seven rare cancers, including MF, was conducted from 1995 to 1998. Patients between 35 and 69 years of age diagnosed with MF (n=140) were recruited, and the diagnoses were verified by a reference pathologist, who classified 83 cases as definitive and 35 cases as possible, 22 cases were not accepted. Of the 118 accepted cases, 104 patients were interviewed (including 76 definitive cases and 28 possible cases). These 76 definitive cases were used for this study. A common set of controls to serve all case groups were interviewed, representing a total of 4574 controls. The latter included 1008 colon cancer patients and 3566 subjects selected from population registers. Information on infections, skin pathology and clinical history 5 years before the diagnosis of MF was used to estimate odds ratios (ORs) derived from logistic regression-modelling, which included gender, age and country. The highest ORs for MF were found in patients who reported a history of psoriasis 5 years before MF was diagnosed (OR 7.2, 95% CI: 3.6-14.5). Urticaria had an OR of 1.4 (95% CI: 0.6-3.6). Infections and atopic diseases were not closely associated with MF. Some diseases correlate to MF. Whether this has a causal background or reflects early diagnostic uncertainty is not known.
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| 8. |
- Vikingsson, Svante, et al.
(författare)
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Rapid Method to Measure Thioguanine Incorporation Into DNA
- 2011
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Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 47:Supplement 1, s. S650-S650
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: The thiopurine drugs, 6-mercaptopurine, azathioprine, and thioguanine, are used in the treatment of acute lymphoblastic leukaemia (ALL). During treatment the thioguanine nucleotides formed are incorporated into the DNA, causing apoptosis due to the cells inability to repair the resulting damage. This mechanism is believed to be important for the effects of thiopurine drugs. We have developed a novel method for the determination of thioguanine incorporation into DNA which is both faster and cheaper than earlier methods.Monitoring the effects of thiopurine treatment by measuring thiopurine metabolites in erythrocytes has proven to be elusive due to the lack of good correlation between measured concentrations and thiopurine effects. If the incorporation is the main mechanism of thiopurine action, a reliable method capable of measuring the incorporation in an ordinary blood sample, such as the method we have developed, should provide a significantly better correlation with treatment effect.Material and Methods: Briefly, DNA extracted from buffy coat is degraded using nuclease P1 and alkaline phosphatase to produce free nucleosides which are purified by filtration. Thioguanosine and thymidine are separated and detected using an LC-MS/MS system and the ratio between the bases provides a measurement of the extent of thioguanine incorporation in DNA. The method has been successfully applied to cell culture samples as well as samples from patients treated orally with thiopurines.Results: In 8 inflammatory bowel disease patients treated with azathioprine the measured incorporation ranged from 2.2 to 8.4 thioguanine bases for every 10 000 thymidine bases (median 5.2). This is in agreement with earlier reports on incorporation in childhood leukemia patients.Conclusions: With the presented method it is possible to determine the incorporation of thioguanine into DNA during thiopurine treatment in a cost effective manner, but further research is needed to determine if there is a place for this type of methods in the monitoring of thiopurine treatment.An ongoing study aims to compare the incorporation to treatment effects as well as conventional measurements of erythrocyte metabolite levels. By this study we hope to determine if incorporation is a more reliable measurement to predict treatment effect and if the erythrocyte metabolite levels correlate with the incorporation.
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| 9. |
- Yen, MA, et al.
(författare)
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Quantifying the potential problem of overdiagnosis of ductal carcinoma in situ in breast cancer screening
- 2003
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Ingår i: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 39:12, s. 1746-1754
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Tidskriftsartikel (refereegranskat)abstract
- The relevance of detection of ductal carcinoma in situ (DCIS) in a breast cancer screening programme, and the extent of overdiagnosis of non-progressive lesions, remains controversial. It was the purpose of this paper to estimate the incidence of non-progressive, 'overdiagnosed' DCIS. We defined non-progressive DCIS (DCIS0) as DCIS which could not have progressed to invasive disease if left untreated. Progressive DCIS (DCIS1) was defined as DCIS which has the propensity to progress to invasive disease. We fitted a Markov process model of the incidence of progressive and non-progressive DCIS, the transition of the former to preclinical invasive disease and the subsequent progression to clinical symptomatic cancer. We used data from the Swedish Two-County Trial and from service screening programmes in the UK, Netherlands, Australia and the USA to estimate the incidence of progressive and non-progressive DCIS, and the detection rates of each at the first and subsequent screening. Average incidence of non-progressive DCIS was 1.11 per 100 000 per year. Average incidence of progressive DCIS was 2.1 per 1000 per year. At prevalence screen, 37% of DCIS cases were estimated to be non-progressive. A woman attending prevalence screen has a 19 times greater chance of having a progressive DCIS or an invasive tumour diagnosed than of having a non-progressive DCIS diagnosed. At incidence screen, only 4% of DCIS cases were estimated to be non-progressive. A woman attending an incidence screen has a 166 times higher probability of having a progressive DCIS or invasive lesion diagnosed than of having a non-progressive DCIS diagnosed. There is an element of overdiagnosis of DCIS in breast cancer screening, but the phenomenon is small in both relative and absolute terms. ⌐ 2003 Elsevier Ltd. All rights reserved.
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| 10. |
- Zhang, Hong, et al.
(författare)
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K-ras mutations in colorectal adenocarcinomas and neighbouring transitional mucosa.
- 1998
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Ingår i: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 34:13, s. 2053-2057
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Tidskriftsartikel (refereegranskat)abstract
- The K-ras gene in codons 12 and 13 was investigated using allele-specific polymerase chain reaction in matched normal mucosa (n = 106), transitional mucosa (n = 69) and tumours (n = 149) from 149 patients with colorectal adenocarcinomas. K-ras mutations in codon 12 were detected in 41/149 (28%) of tumours and 4/69 (6%) of transitional mucosa samples, but not in the normal mucosa. Further, mutation rates were increased in younger patients (P = 0.001) and in mucinous carcinomas (50%) compared with well differentiated (17%), moderately differentiated (26%) or poorly differentiated (24%) tumours. Our findings indicate that mucinous carcinoma may represent a distinct genetic entity.
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