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Biomedical subjects

Bent Ejlertsen

Publications and source records attributed to Bent Ejlertsen.

11 recordsLinked to original sources

Similar efficacy for ovarian ablation compared with cyclophosphamide, methotrexate, and fluorouracil: from a randomized comparison of premenopausal patients with node-positive, hormone receptor-positive breast cancer.

PURPOSE: To compare the efficacy of ovarian ablation versus chemotherapy in early breast cancer patients with hormone receptor-positive disease. PATIENTS AND METHODS: We conducted an open, randomized, multicenter trial including premenopausal breast cancer patients with hormone receptor-positive tumors and either axillary lymph node metastases or tumors with a size of 5 cm or more. Patients were randomly assigned to ovarian ablation by irradiation or to nine courses of chemotherapy with intravenous cyclophosphamide, methotrexate, and fluorouracil (CMF) administered every 3 weeks. RESULTS: Between 1990 and May 1998, 762 patients were randomly assigned, and the present analysis is based on 358 first events. After a median follow-up time of 8.5 years, the unadjusted hazard ratio for disease-free survival in the ovarian ablation group compared with the CMF group was 0.99 (95% CI, 0.81 to 1.22). After a median follow-up time of 10.5 years, overall survival (OS) was similar in the two groups, with a hazard ratio of 1.11 (95% CI, 0.88 to 1.42) for the ovarian ablation group compared with the CMF group. CONCLUSION: In this study, ablation of ovarian function in premenopausal women with hormone receptor-positive breast cancer had a similar effect to CMF on disease-free and OS. No significant interactions were demonstrated between treatment modality and hormone receptor content, age, or any of the well-known prognostic factors.

Adult↗

Semi-quantitative scoring of potentially predictive markers for endocrine treatment of breast cancer: a comparison between whole sections and tissue microarrays.

AIM: To assess whether immunohistochemically stained tissue microarrays (TMA) of 2 mm cores from paraffin embedded tumour tissue may replace whole sections in semi-quantitative evaluation of selected potential markers for endocrine treatment. METHODS: Whole sections and 2 mm cores on TMA were used for immunohistochemical staining of potential markers for endocrine treatment. The Allred scoring system was used for the markers with nuclear localisation: the oestrogen receptor, the progesterone receptor, p27 and the oestrogen receptor co-regulator amplified in breast cancer 1 (AIB1). The Allred scoring system was also used for the non-nuclear markers Bcl-2, pS2 and cyclooxygenase 2 (COX-2); the membrane receptors HER-2, insulin-like growth factor I receptor (IGF-IR) and epidermal growth factor receptor were quantified according to the guidelines for the Herceptest. RESULTS: The data and statistical analyses showed that the semi-quantitative evaluation of oestrogen receptor, progesterone receptor, AIB1, COX-2, HER-2 and IGF-IR on TMA blocks was comparable with analysis on whole sections. CONCLUSIONS: This study shows that semi-quantitative scoring of 2 mm cores on TMA is feasible for several potential markers for endocrine therapy. Considering the small size of many breast tumours, the speed and cost-effectiveness of immunohistochemistry on TMA compared with whole sections, and the importance of the expression level of the proteins, semi-quantitative scoring on TMA has great potential in both retrospective and prospective studies aiming at improving the prediction of response to endocrine treatment.

Antineoplastic Agents, Hormonal↗

[Inherited breast and ovarian cancers].

Most breast and ovarian cancers are sporadic, but approximately 5% are the result of inherited predisposition. Patients and their families may, through genetic risk assessment, be classified as subject to hereditary breast and/or ovarian cancers with an autosomal dominant inheritance. Mutations in the BRCA1 and BRCA2 genes have been identified in most breast and ovarian cancer families, although other genes may be involved. National guidelines for clinical intervention in the cases of high-risk individuals have been established.

Breast Neoplasms↗

retrospective analysis of topoisomerase IIa amplifications and deletions as predictive markers in primary breast cancer patients randomly assigned to cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide, epirubicin, and fluorouracil: Danish Breast Cancer Cooperative Group.

PURPOSE: The aim of the study was to evaluate the predictive value of HER2 and topoisomerase IIalpha gene (TOP2A) for the efficacy of epirubicin in the adjuvant setting of breast cancer patients. PATIENTS AND METHODS: In the Danish Breast Cancer Cooperative Group trial 89D, 980 pre- and postmenopausal primary patients were randomly allocated to either CMF (cyclophosphamide, methotrexate, and fluorouracil; n = 500) or CEF (cyclophosphamide, epirubicin, and fluorouracil; n = 480) times 9, between January 1990 and November 1999. Tumor tissue was retrospectively identified from 805 patients and was analyzed for HER2-positivity and for TOP2A-amplifications and deletions. RESULTS: HER2-positivity was found in 33% of the 805 investigated tumors and was not a predictive marker for epirubicin sensitivity. TOP2A changes were identified in 23% of the 773 investigated tumors: 12% had TOP2A amplifications and 11% had TOP2A deletions. We found that patients with TOP2A amplification had an increased recurrence-free (RFS; hazard ratio [HR], 0.43; 95% CI, 0.24 to 0.78) and overall survival (OS; HR, 0.57; 95% CI, 0.29 to 1.13), respectively if treated with CEF compared with CMF, and that patients with TOP2A deletions had an almost identical hazard ratio (RFS: HR, 0.63; 95% CI, 0.36 to 1.11; OS: HR, 0.56; 95% CI, 0.30 to 1.04). This is in contrast to patients with a normal TOP2A genotype for whom similar outcome was observed in both treatment arms (RFS: HR, 0.90; 95% CI, 0.70 to 1.17; OS: HR, 0.88; 95% CI, 0.66 to 1.17). CONCLUSION: TOP2A amplification-and possibly deletion-seems to be predictive markers for the effect of adjuvant epirubicin containing therapy in primary breast cancer, but a final conclusion has to await a confirmative study or a meta-analysis.

Antigens, Neoplasm↗

Aromatase inhibitors in the treatment of early and advanced breast cancer.

The third generation aromatase inhibitors anastrozole, exemestane, and letrozole have been compared with tamoxifen and other endocrine therapies in several studies in early and advanced breast cancer. These studies are reviewed in this report. Based on the available evidence, the panel recommends that adjuvant treatment with tamoxifen for 5 years should no longer be considered as the sole standard but that a third-generation aromatase inhibitor should be used either alone or in a sequence with tamoxifen in the adjuvant treatment of postmenopausal women with hormone-receptor-positive breast cancer. Third generation aromatase inhibitors may be considered as the first line therapy of hormone-receptor-positive advanced breast cancer in postmenopausal women, and they may also be used for preoperative therapy of breast cancer.

Adult↗

Phase III study of intravenous vinorelbine in combination with epirubicin versus epirubicin alone in patients with advanced breast cancer: a Scandinavian Breast Group Trial (SBG9403).

PURPOSE: To determine whether the addition of intravenous (IV) vinorelbine to epirubicin increased the progression-free survival in first-line treatment of metastatic breast cancer. PATIENTS AND METHODS: A total of 387 patients were randomly assigned to receive IV epirubicin 90 mg/m(2) on day 1 and vinorelbine 25 mg/m(2) on days 1 and 8, or epirubicin 90 mg/m(2) IV on day 1. Both regimens were given every 3 weeks for a maximum of 1 year but discontinued prematurely in the event of progressive disease or severe toxicity. In addition, epirubicin was discontinued at a cumulative dose of 1000 mg/m(2) (950 mg/m(2) from June 1999). Prior anthracycline-based adjuvant chemotherapy and prior chemotherapy for metastatic breast cancer was not allowed. Reported results were all based on intent-to-treat analyses. RESULTS: Overall response rates to vinorelbine and epirubicin, and epirubicin alone, were 50% and 42%, respectively (P =.15). The complete response rate was significantly superior in the combination arm (17% v 10%; P =.048) as was median duration of progression-free survival (10.1 months v 8.2 months; P =.019). Median survival was similar in the two arms (19.1 months v 18.0 months; P =.50). Leukopenia related complications, stomatitis, and peripheral neuropathy were more common in the combination arm. The incidences of cardiotoxicity and constipation were similar in both arms. CONCLUSION: Addition of vinorelbine to epirubicin conferred a significant advantage in terms of complete response rate and progression-free survival, but not in terms of survival.

Adolescent↗

Amplification of HER2 and TOP2A and deletion of TOP2A genes in breast cancer investigated by new FISH probes.

New strategies for improving treatment of patients with breast carcinoma have focused on the HER2 oncoprotein with regard to response to traditional therapy regimes and the effect of a new drug specifically directed against the protein. Furthermore, the status of the topoisomerase IIalpha (TOP2A) gene has been suggested as a predictive marker of anthracycline treatment. In this study of 120 tumours, immunohistochemically detected HER2 overexpression with HercepTest has been compared to the HER2 gene amplification investigated with a new HER2 probe for fluorescence in situ hybridization (FISH). In addition, the HercepTest was evaluated as a screening tool for choosing cases for FISH investigation of TOP2A gene aberrations. The HercepTest score 3+ identified HER2 gene amplification in 27 of 30 amplified tumours (sensitivity of 0.90) with a false-negative rate of 0.10 and a false-positive rate of 0.06. TOP2A gene amplification or deletion was found in 20 cases. Sixteen (80%) of these carcinomas were in the HercepTest 3+ group, but four tumours had alterations in the TOP2A gene with normal HER2 status. Traditionally, in the FISH technique the result has been based on counting 60 cells. However, we found that a much less time-consuming method of counting 60 signals gave equally good results.

Adult↗

[Breast cancer].

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Breast Neoplasms↗