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C Blomqvist

Publications and source records attributed to C Blomqvist.

At least 73 records · Page 4Linked to original sources

Recurrent gains of 1q, 8 and 12 in the Ewing family of tumours by comparative genomic hybridization.

Comparative genomic hybridization (CGH) was used to detect copy number changes of DNA sequences in the Ewing family of tumours (ET). We analysed 20 samples from 17 patients. Fifteen tumours (75%) showed copy number changes. Gains of DNA sequences were much more frequent than losses, the majority of the gains affecting whole chromosomes or whole chromosome arms. Recurrent findings included copy number increases for chromosomes 8 (seven out of 20 samples; 35%), 1q (five samples; 25%) and 12 (five samples; 25%). The minimal common regions of these gains were the whole chromosomes 8 and 12, and 1q21-22. High-level amplifications affected 8q13-24, 1q and 1q21-22, each once. Southern blot analysis of the specimen with high-level amplification at 1q21-22 showed an amplification of FLG and SPRR3, both mapped to this region. All cases with a gain of chromosome 12 simultaneously showed a gain of chromosome 8. Comparison of CGH findings with cytogenetic analysis of the same tumours and previous cytogenetic reports of ET showed, in general, concordant results. In conclusion, our findings confirm that secondary changes, which may have prognostic significance in ET, are trisomy 8, trisomy 12 and a gain of DNA sequences in 1q.

Adolescent↗

Predictive value of c-erbB-2, p53, cathepsin-D and histology of the primary tumour in metastatic breast cancer.

The value of various prognostic factors in breast cancer patients has been determined in a number of studies. Few reports have been published on the dependence of treatment outcome on histological and immunohistochemical characteristics in the primary tumour in patients with metastatic disease. We studied the incidence and prognostic value of histological and molecular abnormalities in the primary tumour of patients who had developed metastatic breast cancer. Eligible patients received a fluorouracil, epirubicin and cyclophosphamide (FEC) regimen either once a week or once every 4 weeks. Adequate specimens for various analyses were available from 127 patients. Median follow-up time of the patients ranged from 15 to 101 months. In this study, the histological grade of the malignancy best predicted response to chemotherapy (P < 0.0005). Most of the responses were observed in patients with grade 1 tumours; in this group, time to progression was delayed. C-erb B-2 gene amplification and oncoprotein expression had no predictive value. Neither p53 nor cathepsin-D predicted treatment outcome after chemotherapy. None of the factors had an effect on overall survival. Among breast cancer patients who received anthracycline-containing chemotherapy, response to treatment correlated with histological grade. In patients with histological grade 1 breast cancer, the time to progression was longest. However, overall survival was not affected by histological grade nor the other parameters tested. In addition to histological grade, other prognostic factors that are not included in this study need to be identified to determine which patients with metastatic breast cancer would benefit from cytotoxic treatment.

Antineoplastic Combined Chemotherapy Protocols↗

Haematological toxicity: a marker of adjuvant chemotherapy efficacy in stage II and III breast cancer.

Two hundred and eleven patients with node-positive stage II and III breast cancer were treated with eight cycles of adjuvant chemotherapy comprising cyclophosphamide, doxorubicin and oral ftorafur (CAFt), with and without tamoxifen. All patients had undergone radical surgery, and 148 patients were treated with post-operative radiotherapy in two randomized studies. The impact of haematological toxicity of CAFt on distant disease-free (DDFS) and overall survival (OS) was recorded. Dose intensity of all given cycles (DI), dose intensity of the two initial cycles (DI2) and total dose (TD) were calculated separately for all chemotherapy drugs and were correlated with DDFS and OS. Patients with a lower leucocyte nadir during the chemotherapy had significantly better DDFS and OS (P = 0.01 and 0.04 respectively). Dose intensity of the two first cycles also correlated significantly with DDFS (P = 0.05) in univariate but not in multivariate analysis, while the leucocyte nadir retained its prognostic value. These results indicate that the leucocyte nadir during the adjuvant chemotherapy is a biological marker of chemotherapy efficacy; this presents the possibility of establishing an optimal dose intensity for each patient. The initial dose intensity of adjuvant chemotherapy also seems to be important in assuring the optimal effect of adjuvant chemotherapy.

Antineoplastic Agents↗

Breast cancer risk estimation in families with history of breast cancer.

Among 288 breast cancer patients (118 with bilateral disease and 165 with diagnosis before 40 years of age), we identified 26 families with a history of breast cancer, including a minimum of three first- or second-degree relatives. Complete pedigrees with verified malignancy data from the Finnish cancer registry were constructed for 22 families. The median age at breast cancer diagnosis of the young probands (< 40 years of age) was 35 years and of bilateral probands was 54 years. The relatives of the young probands were diagnosed with breast cancer at a younger age (median age 54 years) than the relatives of the older (bilateral) probands (median age 60 years). Standard life-table methods were used to compare the risk of breast cancer in the family members with that of the general population. Among the relatives of the young probands, the increased breast cancer risk occurred in the early post-menopausal period, whereas the risk estimate for the relatives of the bilateral probands closely followed that of the general population. In both groups, however, those family members reaching the age of 80 years had a cumulative probability of over 50% of developing breast cancer. The standard life-table method proved useful when assessing the age-specific risk for familial breast cancer, taking into account numerous family members as well as their age at disease onset. This kind of analysis can be performed in populations for which reliable cancer registry data are available. It provides a useful tool for selecting individuals for imaging and mutation screening, counselling and experimental chemoprevention programmes.

Adult↗

Dementia and driving: an attempt at consensus.

The number of older drivers in Sweden will be rapidly increasing during the next decades. A possible relationship exists between the increased relative crash risk of older drivers and the prevalence of age-related diseases such as dementia. However, a clear-cut policy for evaluating driving competence in demented persons is still lacking. In recognition of this fact, the Swedish National Road Administration invited a group of researchers to formulate a consensus on the issue of driving and dementia. This consensus document is aimed at providing primary care physicians with practical advice concerning the assessment of cognitive status in relation to driving. Suggestions are based on a review of existing research and discuss the use of general and driving-specific sources of information available to the physician. Consensus was reached on the statement that a diagnosis of moderate to severe dementia precludes driving and that certain individuals with mild dementia should be considered for a specialized assessment of their driving competence.

Aged↗

Chemical castration induced by adjuvant cyclophosphamide, methotrexate, and fluorouracil chemotherapy causes rapid bone loss that is reduced by clodronate: a randomized study in premenopausal breast cancer patients.

PURPOSE: In the majority of premenopausal breast cancer patients, an adjuvant chemotherapy-induced early menopause occurs, which is known to be a strong predictor of osteoporosis. We present data on the effect of adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) therapy on bone mineral density (BMD) and the efficacy of clodronate on the prevention of bone loss in 148 premenopausal breast cancer patients without skeletal metastases. MATERIALS AND METHODS: Patients were randomized to receive oral clodronate 1,600 mg/d or to a control group. In addition, patients were treated with six cycles of CMF therapy. BMD of the lumbar spine and femoral neck was measured by dual-energy x-ray absorptiometry (DEXA) before therapy and at 1 and 2 years. RESULTS: Changes in the BMD of lumbar spine and femoral neck were -5.9% and -2.0% without clodronate and -2.2% and +0.9% with clodronate at 2 years (P = .0005 and .017, respectively). Patients who developed amenorrhea after chemotherapy had a rapid bone loss, which was significantly reduced by clodronate. In controls, bone loss was 9.5% in the lumbar spine and 4.6% in the femoral neck, while in the clodronate group, bone loss was 5.9% and 0.4%, respectively, at 2 years. Patients with preserved menstruation had only marginal changes in BMD. CONCLUSION: Chemotherapy-induced ovarian failure causes rapid bone loss in premenopausal breast cancer patients. Women older than 40 years are at particularly high risk. Clodronate significantly reduces this bone loss.

Administration, Oral↗

Treatment-related factors predisposing to chronic pain in patients with breast cancer--a multivariate approach.

A study was carried out to assess the factors predisposing to chronic post-treatment pain in the breast area and in the ipsilateral arm in patients treated for breast cancer using two multivariate models. In the study 509 patients with non-metastasized breast cancer who were treated during 1988-1994 completed the questionnaire about pain in the operated breast and in the ipsilateral arm 10-58 months after surgery. The factors included in the analysis were: age, type of operation, size of the tumour, number of lymph nodes removed, involvement of lymph nodes, complications of surgery, intensity of the acute postoperative pain remembered by the patient, number of doses of analgesics, number of months from surgery, adjuvant radiotherapy, chemotherapy and endocrine treatment. The most important factors included in the models of chronic pain were: intensity of the acute postoperative pain, the type of operation, involvement of regional lymph nodes and radiotherapy.

Adult↗

Comparative genomic hybridization of malignant fibrous histiocytoma reveals a novel prognostic marker.

DNA sequence copy number changes were studied by comparative genomic hybridization (CGH) along all chromosomes in 58 samples of malignant fibrous histiocytoma (MFH). The material consisted of 43 primary tumors (9 of myxoid and 34 of storiform-pleomorphic subtype), 13 local recurrences (2 myxoid and 11 storiform-pleomorphic), and 2 metastases (1 myxoid and 1 storiform-pleomorphic). Genetic aberrations, with a mean of 5.5 changes per sample (range, 0 to 22), were detected in 47 of 58 samples (81%). The minimal common regions of the most frequent gains were 1p31 (33%), 9q31 (29%), 5p14-pter (26%), 7q32 (24%), and 7p15-pter (22%). High-level amplifications were detected in 16 of the 58 samples (28%). High-level amplification of 13q31-qter was seen in four tumors (7%); other high-level amplifications were more sporadic. Losses of DNA sequences were less frequent than gains. The minimal common regions of the most common losses were 13q21 (21%) and 13q22 (21%). Statistically significant correlation was found between gain of 7q32 and the rates of worse metastasis-free survival (P = 0.01) and overall survival (P = 0.004). The gain of 7q32 retained its prognostic significance also in a multivariate analysis with tumor size and grade. Gain of 1p31 was associated with a trend to decreased overall survival. Gains of 5p14-pter and 9q31 and losses of 13q21 and/or 13q22 did not have any prognostic value; neither did the total number of aberrations, total number of gains, or total number of losses per sample.

Adult↗

Expression of tenascin in invasion border of early breast cancer correlates with higher risk of distant metastasis.

Tenascin (Tn) is an extracellular matrix glycoprotein transiently expressed in epithelial-mesenchymal interaction areas during embryogenesis. Tn is expressed in a limited manner in adult tissues but emerges during wound healing and tumorigenesis. We have studied Tn expression by immunohistochemistry in 137 small node-negative breast cancers treated with breast-conserving surgery and post-operative radiotherapy during 1985-1989. None of the patients had undergone any adjuvant hormonal therapy or chemotherapy. Stromal Tn expression itself could not predict distant metastasis. However, Tn staining in the area of the invasion border seemed to be a strong predictor of distant metastasis, with an estimated 5-year metastasis-free survival (MFS) of 85% in Tn-positive cases compared to 98% in Tn-negative ones. The prognostic impact of Tn in the invasion border on MFS was stronger than that of tumour size and grade. This staining appears to be a useful adjunct for the estimation of breast-cancer metastasis.

Breast Neoplasms↗

Gains and losses of DNA sequences in liposarcomas evaluated by comparative genomic hybridization.

Comparative genomic hybridization (CGH) was used to detect and map the regions of gain, high-level amplification, and loss of DNA sequences in 14 liposarcomas. Thirteen tumors showed DNA sequence copy number changes of one or more genomic regions (mean, six aberrations/tumor; range, 0-17). These aberrations were observed in almost every chromosome but some chromosomal regions were affected more often than others. DNA sequence gains were more frequent than losses. The most common gain was seen at 12q14-21 (50% of tumors). Other frequent gains (29%) were of 1q21-24, 8cen-q21.2, 19q, and 20q. High-level amplification was observed in six (43%) tumors and included as minimal common segments bands 12q15, 1q22, and 1q24. In five (36%) tumors, sequences at 1q21-24 and 1q32 were found to be gained simultaneously with 12q14-21, which means that in 71% of the tumors with gain at 12q, an increase of DNA sequence copy number at 1q was also observed. The most common losses of DNA sequences (21%) occurred from regions 9p21-pter and 13q21-qter. Most of the aforementioned regions have not previously been reported to be altered in liposarcomas. The detection of a novel recurring amplicon at 1q21-24 with high-level amplification at 1q22 and frequent simultaneous DNA sequence gain at 12q14-21 (high-level amplification at 12q15) suggests that genes linked to both these regions may play a significant role in the development and progression of liposarcomas.

Adult↗

Cytogenetic study of extraskeletal mesenchymal chondrosarcoma. A case report.

Extraskeletal mesenchymal chondrosarcoma (EMC) is a rare and highly malignant type of chondrosarcoma of soft tissue origin. We performed a cytogenetic study on a patient with EMC. Cytogenetic analysis revealed the tumor karyotype: 48-49,XX, t(4;9)(q23;q22), add(10)(q?26), +16, ?del(19)(p13), +1-2mar[cp12] / 48-50,idem, t(1;20)(q21;q13), +mar[cp6] / 46,XX [7].

Adult↗

A randomised trial comparing two doses of the new selective aromatase inhibitor anastrozole (Arimidex) with megestrol acetate in postmenopausal patients with advanced breast cancer.

The aim of this study was to compare the efficacy and tolerability of the new aromatase inhibitor 'ARIMIDEX' (anastrozole) with megestrol acetate in the treatment of advanced breast cancer in postmenopausal women. Anastrozole is a new potent and highly selective non-steroidal aromatase inhibitor. We conducted a prospective randomised trial comparing two doses of anastrozole (1 and 10 mg orally once daily) with megestrol acetate (40 mg orally four times daily) in postmenopausal patients with advanced breast cancer who progressed after prior tamoxifen therapy. All patients were analysed for efficacy as randomised (intention to treat) and for tolerability as per treatment received. Of the 378 patients who entered the study, 135 were randomised to anastrozole 1 mg, 118 to anastrozole 10 mg, and 125 patients to megestrol acetate. After a median follow-up of 192 days, response rate which included complete response, partial response and patients who had disease stabilisation for 6 months or more was 34% for anastrozole 1 mg, 33.9% for anastrozole 10 mg and 32.8% for megestrol acetate. There were no statistically significant differences between either dose of anastrozole and megestrol acetate in terms of objective response rate, time to objective progression of disease or time to treatment failure. The three treatments were generally well tolerated, but more patients on megestrol acetate reported weight gain, oedema and dyspnoea as adverse events while more patients on anastrozole reported gastro-intestinal disorders, usually in the form of mild transient nausea. Patients on anastrozole did not report higher incidences of oestrogen withdrawal symptoms. Anastrozole is an effective and well tolerated treatment for postmenopausal patients with advanced breast cancer. The higher 10 mg dose did not result in additional clinical benefit, but was well tolerated reflecting the good therapeutic margin with anastrozole. Based on this data, anastrozole 1 mg should be the recommended therapeutic dose.

Adult↗

The importance of a multidisciplinary group in the treatment of soft tissue sarcomas.

In 1987, a multidisciplinary soft tissue sarcoma (STS) group was established and a treatment protocol was set up. By 1993, there were 193 patients with a diagnosis of STS of the superficial trunk or extremities. 134 patients were referred with primary (stage M0) tumours and treated with curative or palliative intention. Nine amputations were performed. 94 (70%) patients were treated with wide or compartment surgery (n = 62) or marginal surgery combined with postoperative radiotherapy (n = 32). According to the protocol, these patients had received adequate treatment. 18 patients have recurred locally (13%) (median follow-up: 36 months). 12 were salvaged. 33 had metastases. The estimated 3-year survival, local control and disease-free survival rates are 79, 87 and 69%, respectively. These results compare favourably with previously published results from this hospital and from a nationwide study. The improved results emphasise the importance of a multidisciplinary STS group.

Adolescent↗

Type I and type III collagen metabolites in adult osteosarcoma patients.

Three biochemical markers of collagen metabolism were measured in 39 osteosarcoma patients. The pretreatment values did not predict outcome, and the markers showed no consistent change upon development of metastases. Both the age of the patients and the multimodality therapy affected the collagen metabolites. These findings emphasise the need for cautious interpretation of tumour-associated markers.

Adolescent↗

Markers of type I collagen degradation and synthesis in the monitoring of treatment response in bone metastases from breast carcinoma.

Thirty-six patients with bone metastases included in a trial of supportive calcitonin on the treatment response to systemic therapy were monitored by conventional radiography, conventional indicators of bone metabolism [alkaline phosphatase (AP), osteocalcin (gla), urinary hydroxyproline excretion (OHP), urinary calcium (uCa), serum calcium (sCa)] and collagen metabolites (ICTP, the pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen; PICP, the carboxy-terminal propeptide of type I procollagen; and PIIINP the amino-terminal propeptide of type III procollagen). All patients had been on the same systemic treatment for at least 3 months at the start of the trial. There was a positive correlation between the concentrations of ICTP and PICP at baseline (Spearman's rank-order correlation coefficient rs = 0.62). Both ICTP and PICP showed statistically significant correlations to the other markers of bone metabolism (except sCa and uCa) as well as to the number of bone metastases on bone scans. Reduction in ICTP correlated significantly with the treatment response at three months (rs = - 0.57). while PICP showed a borderline negative correlation to therapy response (rs = - 0.37). Of all the biochemical parameters studied the changes in ICTP showed the best correlation with the treatment response. PICP and ICTP changes in patients with progressive disease differed significantly from those in patients with responding and stable metastases, whereas no difference was found between responders and stable patients.

Antineoplastic Agents↗

Prophylactic filgrastim (G-CSF) during mitomycin-C, mitoxantrone, and methotrexate (MMM) treatment for metastatic breast cancer. A randomized study.

Patients with metastatic breast cancer were randomly assigned to receive as second-line chemotherapy either MMM (mitomycin 8 mg/m2 day 1; mitoxantrone 8 mg/m2 days 1 and 22; methotrexate 35 mg/m2 days 1 and 22) alone or in combination with filgrastim (5 micrograms/kg s.c. days 4-17, 24-37). The courses were repeated every 42 days for a maximum of six courses. Thirty-one patients are evaluable for safety and efficacy. The 16 patients in the filgrastim arm received a total of 42 cycles compared with 34 cycles in the 15 control patients. Tumor responses were few in both patient groups (one partial response in the filgrastim group and two partial responses in control group). Nevertheless, a difference in survival was seen (filgrastim median 10.7 months, control median 6.5 months; p = 0.02 log rank). The treatment was well tolerated. Doses were reduced six times in the filgrastim arm and eleven times in the control arm. Grade IV neutropenia was seen in four patients in the filgrastim arm and in twelve patients in the control arm. The observed survival benefit needs to be confirmed in a larger patient group.

Adult↗