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J Sjöström

Publications and source records attributed to J Sjöström.

17 recordsLinked to original sources
PubMed2005

Cyclin A as a marker for prognosis and chemotherapy response in advanced breast cancer.

We wanted to study cyclin A as a marker for prognosis and chemotherapy response. A total of 283 women with metastatic breast cancer were initially enrolled in a randomised multicentre trial comparing docetaxel to sequential methotrexate-fluorouracil (MF) in advanced breast cancer after anthracycline failure. Paraffin-embedded blocks of the primary tumour were available for 96 patients (34%). The proportion of cells expressing cyclin A was determined by immunohistochemistry using a mouse monoclonal antibody to human cyclin A. Response evaluation was performed according to WHO recommendations. The median cyclin A positivity of tumour cells was 14.5% (range 1.2-45.0). Cyclin A correlated statistically significantly to all other tested proliferation markers (mitotic count, histological grade and Ki-67). A high cyclin A correlated significantly to a shorter time to first relapse, risk ratio (RR) 1.94 (95% CI 1.24-3.03) and survival from diagnosis, RR 2.49 (95% CI 1.45-4.29), cutoff point for high/low proliferation group 10.5%. Cyclin A did not correlate to chemotherapy response or survival after anthracycline, docetaxel or MF therapy. Of all tumour biological factors tested (mitotic count, histological grade and Ki-67), cyclin A seemed to have the strongest prognostic value. Cyclin A is a good marker for tumour proliferation and prognosis in breast cancer. In the present study, cyclin A did not predict chemotherapy response.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

HER2 expression in breast cancer primary tumours and corresponding metastases. Original data and literature review.

The aim of this study was to evaluate whether the HER2 expression in breast cancer is retained in metastases. The HER2 expression in primary tumours and the corresponding lymph node metastases were evaluated in parallel samples from 47 patients. The HercepTest was used for immunohistochemical analyses of HER2 overexpression in all cases. CISH/FISH was used for analysis of gene amplification in some cases. HER2 overexpression (HER2-scores 2+ or 3+) was found in 55% of both the primary tumours and of the lymph node metastases. There were only small changes in the HER2-scores; six from 1+ to 0 and one from 3+ to 2+ when the metastases were compared to the corresponding primary tumours. However, there were no cases with drastic changes in HER2 expression between the primary tumours and the corresponding lymph node metastases. The literature was reviewed for similar investigations, and it is concluded that breast cancer lymph node metastases generally overexpress HER2 to the same extent as the corresponding primary tumours. This also seems to be the case when distant metastases are considered. It has been noted that not all patients with HER2 overexpression respond to HER2-targeted Trastuzumab treatment. The stability in HER2 expression is encouraging for efforts to develop complementary forms of therapy, for example, therapy with radionuclide-labelled Trastuzumab.

Breast Neoplasms↗
PubMed2003

Prognostic value of quality of life scores for time to progression (TTP) and overall survival time (OS) in advanced breast cancer.

The purpose of the study was to investigate whether baseline quality of life (QoL) and changes in QoL scores from baseline are prognostic for time to progression (TTP) and/or overall survival (OS) in patients with advanced breast cancer receiving docetaxel (T) or sequential methotrexate and 5-fluorouracil (MF). QoL was assessed at baseline and before each treatment using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30). Survival curves and probabilities were estimated using the Kaplan-Meier technique. The Cox proportional hazards regression model was used for both the univariate and multivariate analyses to explore relationships between baseline QoL variables and TTP, as well as OS. In the univariate analysis, more severe pain and fatigue at baseline were predictive for a shorter OS; global QoL, physical functioning and appetite loss had a borderline significance (P=0.0130 for global QoL; P=0.0256 for physical functioning: P=0.0149 for appetite loss). World Health Organization (WHO) performance status was significantly predictive for OS. In the multivariate analysis, more severe pain at baseline was predictive for a shorter OS. In contrast, baseline QoL had no prognostic value for the duration of TTP. QoL change scores from baseline QoL predicted neither OS nor TTP. Our findings suggest that while QoL measurements are important in evaluating patients' QoL, they have no great importance in predicting primary clinical endpoints such as TTP or OS in advanced breast cancer patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Tumour microvessel density as predictor of chemotherapy response in breast cancer patients.

The aim of this study was to evaluate the predictive value of intratumoural microvessel density in breast cancer. We studied immunohistochemically primary tumours of 104 patients with metastasised breast cancer who took part in a randomised multicentre trial comparing docetaxel to sequential methotrexate and 5-fluorouracil. Vessels were highlighted with factor VIII staining and counted microscopically. Microvessel density was compared with clinical response to chemotherapy and patient survival. The microvessel density of the primary tumour was not significantly associated with patient's response to chemotherapy, time to progression or overall survival in the whole patient population or in the docetaxel or methotrexate and 5-fluorouracil groups. However, disease-free survival was longer in patients with low microvessel density (P=0.01). These findings suggest that microvessel density of the primary tumour cannot be used as a predictive marker for chemotherapy response in advanced breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

C-erbB-2 expression does not predict response to docetaxel or sequential methotrexate and 5-fluorouracil in advanced breast cancer.

Breast cancer patients with c-erbB-2-positive tumours seem to benefit from anthracycline-based adjuvant chemotherapy. The predictive value of c-erbB-2 for taxane sensitivity is not yet clear. The purpose of this study was to assess whether c-erbB-2 expression is associated with clinical sensitivity to docetaxel (T) or sequential methotrexate and 5-fluorouracil (MF). A total of 283 patients with metastatic breast cancer were initially enrolled in a randomised multicentre trial comparing docetaxel with sequential MF in advanced breast cancer. Paraffin-embedded blocks of the primary tumour were available for 131 patients (46%). c-erbB-2 status was determined by immunohistochemistry using a polyclonal antibody to the c-erbB-2 protein. C-erbB-2 expression was scored in a semi-quantitative fashion using a 0 to 3+ scale. Staining scores 2+ or greater were considered positive. Response evaluation was performed according to World Health Organization (WHO) recommendations. Overall 54 (42%) patients had c-erbB-2-positive tumours. There was no association between treatment outcome and c-erbB-2 overexpression. The overall response rates (RR) (n=128) among c-erbB-2-negative and -positive patients were 35 and 44%, respectively (P=0.359). In the MF arm (n=62), the RR was somewhat higher in the c-erbB-2 overexpressors (33% versus 18%, P=0.18). In the docetaxel arm the RRs were very similar, regardless of the c-erbB-2 expression (53% versus 53%). While several studies have suggested a prognostic and putative predictive significance of c-erbB-2 overexpression in early breast cancer, the significance of c-erbB-2 expression as a predictive factor for response to various cytotoxic treatments in advanced breast cancer is still controversial. In this study, c-erbB-2 expression could not predict response to either MF or T. Thus, tumours over-expressing c-erbB-2 are not uniformly more sensitive to taxanes and c-erbB-2 expression cannot yet be applied clinically as a predictive factor for response in advanced breast cancer.

Adolescent↗
PubMed2001

Timing of quality of life (QoL) assessments as a source of error in oncological trials.

AIM OF THE STUDY: To produce an empirical estimate of the nature and magnitude of the error produced by incorrect timing quality of life (QoL) measurements in patients receiving chemotherapy. DESIGN: In a multicentre trial, 283 patients were randomized to receive either docetaxel (T) or sequential methotrexate and 5-fluorouracil (MF). The QoL was assessed at baseline and before each treatment using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). The study design was retrospective. Data were analysed using t-tests. RESULTS: Erroneous timing affected the QoL findings in both treatment arms. At baseline, there were statistically significant differences in the MF group on the nausea/vomiting scale, with ill-timed assessment showing more symptoms, and in the T group on the physical functioning scale with ill-timed assessments indicating better QoL. The mean scores of correct vs. incorrect timings over the first 14 cycles showed statistically significant differences on several scales. In the MF group, ill-timed assessments indicated significantly worse physical functioning and global QoL, and significantly more of the following symptoms: fatigue, nausea/vomiting, insomnia, appetite loss, and constipation. In the T group, ill-timed assessment showed better physical functioning, less dyspnoea and more insomnia than correctly timed assessments. The reasons for erroneous timing were not always detectable retrospectively. However, in some cases the MF group, being in standard treatment, seemed to have followed a clinical routine not involving the active participation of the study nurse responsible, whereas patients in the experimental T group were more consistently taken care of by the study nurses. CONCLUSIONS: Incorrect timing of QoL assessments in oncological trials jeopardises both the reliability of the QoL findings within treatment and the validity of QoL outcome comparisons between treatments. This issue should be emphasized in the planning of both the study design and clinical routines.

Activities of Daily Living↗
PubMed2001

Serum tumour markers CA 15-3, TPA, TPS, hCGbeta and TATI in the monitoring of chemotherapy response in metastatic breast cancer.

The clinical utility of CA 15-3, polypeptide specific antigen (TPS), tissue polypeptide antigen (TPA), human chorionic gonadotropin (hCGbeta) and tumour-associated trypsin inhibitor (TATI) as indicators of chemotherapy response was assessed in advanced breast cancer. Serum was prospectively collected in one center before treatment (after the first course of chemotherapy) and at response evaluation from 57 patients taking part in a multicentre randomized trial comparing docetaxel with sequential methotrexate and 5-fluorouracil in the treatment of advanced breast cancer. The pretreatment levels of the serum markers were not predictors of the later response to treatment. Changes in the TPS level showed the strongest association with clinical response after the first course of chemotherapy and CA 15-3 at the best response evaluation. However, distinct mismatches occurred with every marker. The most problematic error was an increase in marker levels in patients with clinical responses, which might have caused interruption of therapy. This occurred in 8% and 17% of patients after the first course of chemotherapy and in 4% and 17% of patients at the best response evaluation with CA 15-3 and TPS, respectively. Moreover, after the first course of chemotherapy only 39% and 33% of the patients with progressive disease could be identified on the basis of increasing levels of CA 15-3 and TPS. respectively. Later, at clinical disease progression, TPA and TPS were found to be better indicators of disease progression than CA 15-3. In conclusion, changes in CA 15-3 or TPS levels usually correlate with clinical response, but owing to distinct discordances, they should not be used as sole indicators of response to chemotherapy in advanced breast cancer.

Adult↗
PubMed2000

Quality of life in patients with metastatic breast cancer receiving either docetaxel or sequential methotrexate and 5-fluorouracil. A multicentre randomised phase III trial by the Scandinavian breast group.

The purpose of this study was to evaluate the effects of two alternative chemotherapy regimes on the quality of life (QoL) of patients with advanced breast cancer. In a multicentre trial, 283 patients were randomised to receive either docetaxel (T) or sequential methotrexate and 5-fluorouracil (MF). QoL was assessed at baseline and before each treatment using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30). Initial compliance in the QoL study was 96% and the overall compliance 82%. QoL data were available for 245 patients (T 130 and 115 MF). Both treatment groups showed some improvement in emotional functioning during treatment, with a significant difference favouring the MF group at treatment cycles 5 and 6. In the T group, the scores on the other functional scales remained stable throughout the first six cycles. There were significant differences favouring the MF group on the social functioning scale at treatment cycle 6 and on the Global QoL scale at treatment cycles 5 and 6. On most symptom and single-item scales there were no statistically significant differences between the groups. However, at baseline, the T patients reported more appetite loss, at treatment cycles 2-4, the MF patients reported more nausea/vomiting, and at treatment cycle 6, the T patients reported more symptoms of fatigue, dyspnoea and insomnia. There were no statistically significant differences between the groups in the mean change scores of the functional and symptom scales. Interindividual variance was, however, larger in the T group. Differences in QoL between the two treatment groups were minor. Hence, given the expectancy of comparable QoL outcomes, the choice of treatment should be made on the basis of the expected clinical effect.

Algorithms↗
PubMed2000

Influence of TNT transformation on microbial community structure in four different lake microcosms.

After World War II, large amounts of obsolete ammunition were dumped in various lakes in Sweden. Trinitrotoluene, TNT, was one of the main components of the dumped explosives. In this study, four different lake microcosms originating from lakes where relatively large amounts of ammunition were dumped were used to mimic the effect of TNT release on the natural microbial community. Increased microbial growth was found in lake microcosms amended with TNT. However, negligible mineralization of TNT was detected, suggesting that TNT was not utilized as a carbon source, but as a nitrogen source. Random amplified polymorphic DNA (RAPD) analysis indicated that the TNT induced no significant differences in microbial community composition and therefore, no major changes in natural selection, despite the increased microbial growth in the presence of the compound. More than 95% of the added TNT bound irreversibly to the sediments, possibly as a result of microbial transformation to reactive metabolites that subsequently bound covalently to components of the sediment. The results, taken together, suggest that no permanent change in the microbial ecology occurred as a result of the TNT amendment. This was probably due partly to the transient exposure of the microbial communities to the TNT before it became irreversibly bound to the sediment, and partly to the fact that TNT was not a primary growth substrate that strongly affects natural selection.

Bacteria↗
PubMed2000

Newly diagnosed latent autoimmune diabetes in adults (LADA) is associated with low level glutamate decarboxylase (GAD65) and IA-2 autoantibodies. Diabetes Incidence Study in Sweden (DISS).

A quantitative assay with microSepharose was used to determine GAD65Ab and IA-2Ab levels in 771 population-based patients diagnosed with diabetes mellitus at 15 to 34 years of age, and in 828 matched controls. Among the patients, 587 (76%) were classified with type I, 108 (14%) with type II, and 76 (10%) with unclassifiable diabetes. The levels above normal demonstrated a prevalence of GAD65Ab in 66% of type I diabetes, 50% of type II diabetes and 54% of unclassifiable patients and for IA-2Ab in 40%, 17% and 21%, respectively. Among the autoantibody-positive sera, the LADA patients had a lower GAD65Ab index (median 0.19, p < 0.0001) and IA-2Ab index (median 0.28, p < 0.0001) than the type I patients (median 0.37 and 0.66). Patients with unclassifiable diabetes had a GAD65Ab (median 0.43) or IA-2Ab (median 0.63) index which was not different from the type I diabetes patients. Our data demonstrate that young adult new-onset LADA patients have low level GAD65Ab and IA-2Ab. The low-level autoantibodies may signify a less aggressive beta-cell autoimmunity, which may explain why these patients are often classified with type II or non-insulin-dependent diabetes.

Adolescent↗
PubMed2000

Predictive value of p53, mdm-2, p21, and mib-1 for chemotherapy response in advanced breast cancer.

p53 is a transcription factor that participates in cell cycle checkpoint processes and apoptosis. The protein product of the murine double minute gene 2 (mdm-2) plays a central role in the regulation of p53. In response to DNA-damaging agents, the wild-type p53-activated fragment 1 (WAF1 also known as p21) is an important downstream effector in the p53-specific growth arrest pathway. In breast cancer patients, it is unclear whether measuring p53, mdm-2, or p21 expression provides information on how patients will respond to chemotherapy. Mib-1 monoclonal antibody recognizes the proliferation-related antigen Ki-67. High tumor proliferation has previously been associated with response to chemotherapy. p53, mdm-2, p21, and mib-1 expression were assessed by immunohistochemical methods in primary tumors derived from 134 patients who took part in a randomized multicenter trial comparing docetaxel to sequential methotrexate and 5-fluorouracil (MF) in advanced breast cancer. Low mib-1 staining correlated with negative p53 staining (P = 0.001), and mdm-2 and p21 stainings correlated positively with each other (P < 0.001). p53, mdm-2, p21, and mib-1 expression were not significantly associated with response to chemotherapy, time to progression, or overall survival in the whole patient population or in the docetaxel group. However, in the MF group, a low mib expression (<25%) and a high mdm-2 expression (> or =10%) predicted a better response (P = 0.014 and P = 0.046, respectively) to treatment and a longer time to progression in both univariate and multivariate analyses. p53 staining status was not associated with response to treatment in either group. Interestingly, tumors with both negative mdm-2 and p21 expression, irrespective of p53 status, had a high response rate to docetaxel but no response to MF. Although highly preliminary, the findings suggest that different tumor biological factors may predict response to different chemotherapy regimens with distinct mechanisms of action. The results of our phenotype analysis also indicate that it is more likely that a panel of tumor biological factors instead of only one single factor may be needed for better prediction of chemotherapy response.

Adolescent↗
PubMed1999

Docetaxel compared with sequential methotrexate and 5-fluorouracil in patients with advanced breast cancer after anthracycline failure: a randomised phase III study with crossover on progression by the Scandinavian Breast Group.

The aim of this study was to compare the efficacy and tolerability of docetaxel to methotrexate and 5-fluorouracil in advanced breast cancer after anthracycline failure. A randomised multicentre trial was conducted in 283 patients with advanced breast cancer who had failed previous anthracycline treatment. Docetaxel at a dose of 100 mg/m2 every 3 weeks (n = 143) was compared with sequential methotrexate and 5-fluorouracil (MF; n = 139) given at day 1 and 8 every 3 weeks at dosages of 200 mg/ m2 and 600 mg/m2, respectively. After progression, crossover to the alternative treatment group was recommended. There was a significantly higher overall response rate in the docetaxel 42% (CR 8% + PR 34%) than in the MF arm 21% (CR 3% + PR 18%) (P < 0.001). The median time to progression (TTP) was 6.3 months in the docetaxel arm and 3.0 months in the MF arm (P < 0.001). Docetaxel also had a significantly higher response rate of 27% following crossover compared with MF (12%). Significantly more side-effects (leucopenia, infections, neuropathy, oedema, asthenia, skin, nail changes, alopecia) were seen in the docetaxel than in the MF group. However, grade 3 and 4 side-effects were infrequent with both drugs, with the exception of fatigue, alopecia and infections. Median overall survival (OS) including crossover phase was 10.4 months in the docetaxel and 11.1 months in the MF arm (P = 0.79). Based on the response rate and the primary endpoint of TTP, docetaxel is superior to sequential methotrexate and 5-fluorouracil in advanced breast cancer after anthracycline failure.

Adult↗
PubMed1998

A multivariate analysis of tumour biological factors predicting response to cytotoxic treatment in advanced breast cancer.

The study was designed to identify factors that could predict response to chemotherapy in breast cancer. A total of 173 patients with measurable or evaluable metastatic breast cancer were enrolled in a randomized trial between November 1987 and January 1991 to receive a monthly dose of 5-fluorouracil (500 mg m(-2)), epirubicin (60 mg m(-2)) and cyclophosphamide (500 mg m(-2)) either administered in four weekly doses or in an every-4-week dose as first-line cytotoxic treatment. In 103 evaluable patients we performed a multivariate analysis of the tumour biological factors, i.e. histological grade, oestrogen receptor (ER), progesterone receptor (PR), S-phase fraction (SPF), ploidy, p53, c-erbB-2, Bcl-2 and Bax expression, which showed significance in the univariate analysis according to treatment response, time to progression (TTP) or overall survival (OS). In the univariate analysis only SPF, grade and the proapoptotic protein Bax correlated with the response to cytotoxic treatment. In the multivariate analysis SPF had the strongest correlation, followed by grade and Bax. In the univariate analysis grade, PR, Bax and Bcl-2 correlated significantly with TTP, whereas in the multivariate analysis only PR showed a statistically significant correlation. In the univariate analysis PR and Bax correlated with OS and both retained its significance in the multivariate analysis. The factors that correlated significantly with the response to cytotoxic treatment in the univariate analysis, i.e. grade, SPF and Bax, seemed to predict independently the response to treatment in the multivariate analysis also. TTP and OS could be predicted partly by the same factors, although the association was quite weak. More studies and new tumour biological factors are needed to identify the group of breast cancer patients who get the most benefit from chemotherapy.

Analysis of Variance↗