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Biomedical subjects

C Blomqvist

Publications and source records attributed to C Blomqvist.

At least 55 records · Page 3Linked to original sources

Post-mastectomy radiotherapy in pT3N0M0 breast cancer: is it needed?

BACKGROUND AND PURPOSE: It is not been established whether breast cancer patients who have a primary tumor 5 cm or larger but no axillary nodal or distant metastases at the time of the diagnosis (pT3N0M0) benefit from post-operative radiation therapy after mastectomy. MATERIAL AND METHODS: We identified 81 patients with T3N0M0 breast cancer out of the total of 4190 breast cancer patients treated in one university radiotherapy department from 1987 to 1994 from the department patient registry, and examined the clinical records and histopathological slides. RESULTS: Only 38 of the 81 patients had true pT3N0M0 breast cancer after the review (0.9% of the 4190 new breast cancer patients registered in the department from 1987 to 1994). Three (60%) of the five patients who were not treated with post-operative radiation therapy developed locoregional recurrence of breast cancer as compared with only three (9%) of the 33 patients who were given post-operative radiotherapy during a median follow-up of 58 months (P = 0.0003). Patients who were given post-operative radiotherapy had a better distant disease-free survival rate (P = 0.04) and overall survival rate (P = 0.03) than the ones who were not treated with radiation therapy after surgery. Of the 29 patients who had chest wall irradiation only, one had in-field recurrence at the surgical scar, one both at the scar and the unirradiated axilla, and only one (3%) solely in the axilla. CONCLUSIONS: Patients with true pT3N0M0 breast cancer are rare. The results suggest that women with pT3N0M0 breast cancer benefit from post-operative radiotherapy, but the value of irradiating the dissected ipsilateral axilla remains unsettled.

Adult↗

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↗

Cathepsin-D, urokinase plasminogen activator and type-1 plasminogen activator inhibitor in early breast cancer: an immunohistochemical study of prognostic value and relations to tenascin-C and other factors.

Cytosolic determinations of cathepsin-D (cath-D), urokinase plasminogen activator (uPA) and its specific inhibitor PAI-1 have shown an association with adverse prognosis in breast cancer. Our aim was to study the distribution of these markers in small axillary node-negative breast carcinomas using immunohistochemistry and relate the semiquantitative results to known prognostic factors, the expression of tenascin-C (Tn-C) in invasion border of the tumour and prognosis. All the 158 women (159 tumours) were treated with breast conserving surgery and postoperative radiotherapy. Cytoplasmic immunoreactivity for cath-D was seen in carcinoma cells in 47% and in stromal cells in 44%. Nearly all tumours expressed uPA and PAI-1, which were categorized to cytoplasmic expression in carcinoma cells and diffuse stromal expression and quantified -/+/++/ and further dichotomized for purposes of analysis. Expression of uPA and PAI-1 in stromal fibroblasts was recorded as -/+. Cytoplasmic and stromal cell cath-D contents were associated with grade, proliferation, Tn-C expression in the tumour invasion border and the development of distant metastasis. In multivariate analysis stromal cath-D proved to be an independent prognostic factor for metastasis. Stromal expression of uPA was associated with an increased risk of local recurrence; otherwise high levels of uPA did not associate with other prognostic factors nor with prognosis. Fibroblastic expression of PAI-1 showed an association with both local and distant disease recurrence. However, no consistent association between the immunohistochemically quantified uPA and PAI-1 and prognosis was found. In conclusion, immunohistochemical determination of cath-D seems to be a viable method to predict a higher risk of metastasis but not local recurrence in small axillary node-negative breast carcinomas.

Biomarkers↗

Leucocyte nadir as a marker for chemotherapy efficacy in node-positive breast cancer treated with adjuvant CMF.

The purpose of this study was to examine the association between the leucocyte nadir and prognosis in breast cancer patients receiving adjuvant chemotherapy consisting of cyclophosphamide, methotrexate and fluorouracil (CMF). Three hundred and sixty-eight patients with node-positive breast cancer without distant metastases were treated with six cycles of adjuvant CMF. Some patients (n = 60) also received tamoxifen. All patients underwent surgery and received radiotherapy to the axillary and supraclavicular lymph nodes and the chest wall. The effect of leucopenia caused by CMF on distant disease-free survival (DDFS) and overall survival (OS) was assessed. A low leucocyte nadir during the chemotherapy was associated with a long DDFS in univariate analysis when tested as a continuous variable (the relative risk (RR) 1.3, 95% confidence interval (CI) 1.04-1.06, P = 0.02). Similarly, when the leucocyte nadir count was divided into tertiles, the patients who had the highest nadir values during the six-cycle treatment had worst outcome (RR 1.6, 95% CI 1.07-2.5, P = 0.02). However, in a multivariate analysis only the number of affected lymph nodes, tumour size, progesterone receptor status, surgical procedure, age and adjuvant tamoxifen therapy retained prognostic significance, whereas the leucocyte nadir count did not. A low leucocyte nadir during the adjuvant CMF chemotherapy is associated with favourable DDFS and it may be a useful biological marker for chemotherapy efficacy.

Adult↗

Chronic post-treatment symptoms in patients with breast cancer operated in different surgical units.

AIMS: This study was designed to find out whether women operated in high volume surgical units have less chronic symptoms than women operated in smaller volume units. METHODS: A questionnaire was sent to 265 consecutive women treated at the Department of Oncology, Helsinki University Central Hospital, from January to June 1996. Of the patients, 129 were operated in hospitals experienced in breast cancer surgery (high volume units = HVU) and 92 patients in district hospitals with less experience in breast surgery (low volume units = LVU). RESULTS: Chronic symptoms were less common in HVU than in LVU: chronic pain (56 vs. 43%, P<0.05) or strange sensations (45 vs. 26%, P<0.01) in the ipsilateral arm or phantom sensations in the removed breast (66 vs. 26%, P<0.001). The risk factors included in the multivariate model for chronic pain in the breast area were: intensity of acute post-operative pain, radiotherapy and depression and for the chronic arm pain: low volume unit and depression. CONCLUSIONS: More careful surgical technique seems to reduce the risk of chronic pain following treatment of breast cancer. Chronic pain is associated with more intense post-operative pain and depression.

Adult↗

FEC mobilized stem cells for high-dose therapy in breast cancer patients. SB6 9401 Study Group.

The feasibility of mobilizing peripheral blood stem cells (PBSC) using anthracycline containing polychemotherapy and G-CSF on the first 50 patients randomized to the high-dose arm in the adjuvant SBG 9401 is investigated. The patients were treated with standard FEC (5-fluorouracil 600 mg/m2, epirubicin 60 mg/m2, cyclophosphamide 600 mg/m2) for two courses followed by a modified third FEC course with a C dose of 1200 mg/m2 supported with subcutaneous G-CSF (filgrastim) at 5 mg/kg followed by harvest around day 11. The mean yield of CD34+ cells per patient was 10.6x10(6)/kg (range 2.6-29.1). The side effects after the third course were low and only one patient developed an uncomplicated granulopenic fever. Our data indicated a correlation between number of transfused CD34+ cells and days to neutrophil and platelet recovery. In conclusion, the modified FEC regimen followed by G-CSF is a feasible method for PBSC mobilization in the adjuvant setting.

Antigens, CD34↗

Chemotherapy in Ewing's sarcoma. The Scandinavian Sarcoma Group experience.

During the past 15 years the Scandinavian Sarcoma Group has treated 140 patients with Ewing's sarcoma. Two protocols have been used. SSG IV included 52 patients between 1984 and 1990 and SSG IX, 88 patients since 1990. After 5 years of treatment, local recurrences occurred in 19% of the patients (M0 + M1) in the SSG IV group and 10% in the SSG IX group. Distant metastases developed in 57% of the M0-patients in the SSG IV group and in 33% in the SSG IX group. Tumor-related survival (overall) of M0-patients was 49% in SSG IV and 70% in SSG IX, and the metastasis-free survival rate 45% and 58%, respectively. Patients having a localized extremity tumor had a survival rate of 90% (SSG IX). In both treatment groups, good responders to chemotherapy had a better survival rate than poor ones (SSG IV, p < 0.02, GI-II vs. G II-IV and SSG IX, p < 0.003, GI-III vs. G IV). In conclusions local control and survival rates were better with SSG IX than SSG IV.

Adolescent↗

Aminoterminal propeptide of type I procollagen (PINP) correlates to bone loss and predicts the efficacy of antiresorptive therapy in pre- and post-menopausal non-metastatic breast cancer patients.

The aim of this study was to determine the correlation between changes in collagen metabolites (ICTP, mature cross-linked carboxy-terminal telopeptide of type I collagen; PINP, the amino-terminal propeptide of type I procollagen) and bone mineral density (BMD) in 206 pre- and post-menopausal breast cancer patients with non-metastatic disease. All patients received adjuvant cancer treatment--premenopausal patients chemotherapy and post-menopausal patients anti-oestrogens. In addition, the patients were also randomized to receive oral clodronate 1600 mg daily for 3 years. BMD was measured at baseline and at 1 and 2 years, the collagen metabolites at baseline and at 1 year. There was a highly significant negative correlation between the changes in PINP and BMD in lumbar spine and femoral neck from baseline to 12 months in all patients (r(s) = -0.68, P < 0.0001, and -0.45, P < 0.0001, respectively), and in pre- and post-menopausal patients separately. The changes in PINP levels at 12 months predict further changes in BMD at 24 months (r = -0.70, P < 0.0001, and -0.51, P < 0.0001, respectively). ICTP and BMD changes correlated significantly only in lumbar spine of premenopausal patients who developed rapid bone loss due to chemotherapy-induced amenorrhoea (r(s) = -0.34, P = 0.0003). The PINP levels at 12 months were significantly lower in the clodronate group than in the control group (P < 0.0001). Our results indicate that PINP is a sensitive marker of bone turnover rate. Changes in PINP levels significantly predicted changes in BMD and correlated with the antiresorptive efficacy of clodronate treatment.

Bone Density↗

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↗

Tenascin-C expression in invasion border of early breast cancer: a predictor of local and distant recurrence.

We have recently demonstrated an association between distant metastasis and the expression of the extracellular matrix glycoprotein tenascin-C (Tn-C) in the invasion border of small axillary node-negative breast carcinomas. Our purpose was to assess the relationship between the expression of Tn-C in the tumour invasion border and several histopathological and biological variables and to compare their usefulness in predicting local and distant disease recurrences. The original patient group consisted of 143 women with axillary node-negative breast cancer (one bilateral) treated with breast-conserving surgery and post-operative radiotherapy, and followed for a median of 8 years. Because of the small number of recurrences an additional group of 15 similarly treated women with recurrent breast cancer was also studied. The size of the tumour, its histology, including a possible intraductal component, and grade were re-evaluated. The expression of erbB-2, p53, Ki-67 and Tn-C was evaluated by immunohistochemistry. Ploidy and S-phase fraction (SPF) were assessed by flow cytometry. The only statistically significant prognostic factor for local recurrence was Tn-C expression in the invasion border. For metastasis Ki-67 positivity, tumour size and Tn-C expression in the invasion border were statistically significant, but Ki-67 positivity was the only independent prognostic factor. Tn-C expression in the invasion border was associated with a higher proliferation rate measured by Ki-67 and SPF, which is consistent with the suggested growth-promoting activity of Tn-C. Tn-C may be a useful marker in selecting patients for adjuvant therapies to reduce the rate of both local and distant cancer recurrences.

Adult↗

Biweekly dose escalation in curative accelerated hyperfractionation for advanced head and neck cancer: a feasibility study.

PURPOSE: To study the feasibility of a dose-escalated accelerated hyperfractionation schedule for patients with advanced head and neck cancer. MATERIALS AND METHODS: Twenty-nine previously untreated patients with advanced squamous cell carcinoma were treated with the following biweekly dose-escalated accelerated hyperfraction schedule: during the first 2 weeks 1.2 Gy twice a daily (bid) up to 24 Gy, thereafter during the next following 2 weeks 1.4 Gy bid to 28 Gy in 20 fractions, and thereafter 22.4 Gy in 1.6 Gy bid fractions during 1 1/2 weeks. Thus, the the total dose was 74.4 Gy in 54 fractions given in 5 1/2 weeks. RESULTS: The planned total dose was given within the planned time to 19 (66%) patients. For seven patients the treatment time was prolonged with 1 to 6 days because of department closure for holidays or machine-down days, and in three cases the treatment time was prolonged more than 8 weeks. When the tumor responses were evaluated at 3 months after given radiotherapy, 27 (93%) patients showed complete tumor clearance, 1 patient had a recidual focus, and 1 patient showed progressive disease. The ultimate 1-, 2-, and 3-year local control rates were: 87, 71, and 60%. Four patients had a salvage laryngectomy. The 1-, 2-, and 3-year survival rates for all patients were as follows: 96, 81, and 73%. All patients developed confluent mucositis, 15 patients were hospitalized for nutritional support, and 11 patients had moist desquamation. However, all acute reactions healed completely, and no serious late complications were observed. CONCLUSIONS: This is a safe and effective treatment schedule for patients with advanced head and neck cancer.

Adult↗

Complexity of 12q13-22 amplicon in liposarcoma: microsatellite repeat analysis.

The 12q13-22 amplicon from four liposacroma specimens evaluated by comparative genomic hybridization was studied analyzing 55 microsatellite markers by PCR. All four specimens were informative in at least 34 loci; an amplification or allelic imbalance was identified with four to 17 markers. The amplicons were discontinuous; there were non-amplified marker loci between the amplified marker loci. These findings indicate the presence of separate amplicons in the 12q13-22 region. Evidence of the concomitant gain of one allele and loss of the other allele was found with several markers in one tumor and with one marker in two tumor specimens. Southern blotting showed amplification of CDK4 and MDM2 in all four specimens.

Alleles↗

Overrepresentation of 1q21-23 and 12q13-21 in lipoma-like liposarcomas but not in benign lipomas: a comparative genomic hybridization study.

Twenty lipomatous tumors, including eight lipoma-like liposarcomas and 12 benign lipomas, were analyzed using comparative genomic hybridization (CGH). DNA sequence copy number changes detected in five lipoma-like liposarcomas (mean, 1.1 aberrations/tumor; range, 0-2) consisted of gains of 12q13-21 (five tumors) and 1q21-23 (four tumors). Two of the tumors showed high-level amplification at 12q14-21 and one tumor at 1q21-22. No copy number changes were found in lipomas. Overrepresentation of 1q and 12q sequences was a recurrent finding in lipoma-like liposarcomas but not in lipomas. Thus, CGH may help in the differential diagnosis of low-grade or borderline adipose neoplasms.

Adult↗

The outcome of advanced soft tissue sarcoma patients with complete tumour regression after either chemotherapy alone or chemotherapy plus surgery. The Scandinavian Sarcoma Group experience.

The intensified induction regimens used and the potential use of high-dose consolidation chemotherapy (CT) in advanced soft tissue sarcomas (STS) has focused interest on the outcome of those patients who can achieve complete remission (CR) by current therapy. The files from four institutions with a special interest in STS were studied. 38 adult patients with advanced STS who were converted disease-free by either CT alone (n = 14) or CT followed by surgery (n = 24) were found. The median follow-up time was 29 months. The median disease-free survival (DFS) was 18 months and the estimated 2-year DFS 34%. The median disease-specific survival (DSS) was 40 months and the estimated 2-year DSS 78%. For patients who achieved CR by CT alone, and for patients who were converted to CR by surgery, the corresponding DFS figures were 23 months (estimated 2 year DFS 48%) and 10 months (26%) (P = 0.07), respectively. The histological response to CT significantly predicted outcome in patients subjected to surgery (DFS P value 0.004, DSS P value 0.02). Patients who achieved CR by surgery shortly after having achieved a clinical partial response (PR with early surgery) did better than those who where converted to CR by surgery after protracted CT following a clinical PR (PR with late surgery) (DFS P value 0.02, DSS P value 0.1). Our results confirm that CT alone can induce prolonged DFS in rare patients with advanced STS. In patients subjected to surgery, a good histological response indicates improved outcome.

Adolescent↗

Clodronate improves bone mineral density in post-menopausal breast cancer patients treated with adjuvant antioestrogens.

The effect of clodronate on bone mineral density (BMD) was studied in 121 post-menopausal breast cancer women without skeletal metastases. In addition, two antioestrogens, tamoxifen and toremifene, were compared in their action on bone mineral density. Patients were randomized to have an adjuvant antioestrogen treatment either 20 mg of tamoxifen or 60 mg of toremifene daily for 3 years. In addition all patients were randomized to have 1600 mg of oral clodronate daily or to act as control subjects. BMD of the lumbar spine and femoral neck were measured by dual-energy radiographic absorptiometry before therapy and at 1 and 2 years. At 2 years, clodronate with antioestrogens markedly increased BMD in the lumbar spine and femoral neck by 2.9% and 3.7% (P = 0.001 and 0.006 respectively). There were no significant changes in BMD in the patients given antioestrogens only. No significant differences were found between tamoxifen and toremifene on bone mineral density. Clodronate with antioestrogens significantly increased bone mass in the lumbar spine and femoral neck. Both antioestrogens, tamoxifen and toremifene, similarly prevented bone loss in the lumbar spine and femoral neck.

Analysis of Variance↗