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Biomedical subjects

H T Mouridsen

Publications and source records attributed to H T Mouridsen.

At least 19 recordsLinked to original sources
PubMed1998

Doxorubicin vs epirubicin, report of a second-line randomized phase II/III study in advanced breast cancer. EORTC Breast Cancer Cooperative Group.

The EORTC Breast Cancer Cooperative Group carried out a randomized trial to compare doxorubicin with epirubicin as second-line chemotherapy in patients with metastatic breast cancer. Two hundred and fifty-nine patients with at least one site of metastatic disease entered this trial, of whom 232 patients were eligible. Treatment consisted of doxorubicin 75 mg m(-2) or epirubicin 90 mg m(-2) i.v. every 3 weeks. The overall response rates for doxorubicin and epirubicin were 36% and 28% respectively (P = 0.173). The median time to progression was 23 weeks for doxorubicin and 19 weeks for epirubicin (P = 0.063) and the median duration of response was 40 weeks for doxorubicin and 32 weeks for epirubicin (P = 0.059). The median survival was 47 weeks for doxorubicin and 44 weeks for epirubicin (P = 0.196). Leucocyte count on retreatment day (P = 0.011) and platelet nadir (P = 0.031) were significantly lower in the doxorubicin-treated group. Also mucositis (P < 0.001), diarrhoea (P = 0.005) and haemorrhage (P = 0.048) were significantly worse in the doxorubicin arm. Nine patients on doxorubicin and two patients on epirubicin experienced congestive heart failure (CHF). At the dose levels used in this study, no statistical differences in response rate and survival were found between the two treatment arms. Treatment with doxorubicin tended to result in a slightly longer duration of response and time to progression but doxorubicin was more toxic than epirubicin.

Adult↗
PubMed1997

Time since childbirth and prognosis in primary breast cancer: population based study.

OBJECTIVE: To investigate whether time since birth of last child was of prognostic importance in women with primary breast cancer. DESIGN: Retrospective cohort study based on a population based database of breast cancer diagnoses with detailed information on tumour characteristics, treatment regimens, reproductive factors, and vital status. SETTING: Denmark. SUBJECTS: 5652 women with primary breast cancer aged 45 years or less at the time of diagnosis. MAIN OUTCOME MEASURES: 5 and 10 year survival; relative risk of dying. RESULTS: Women diagnosed in the first 2 years after last childbirth had a crude 5 year survival of 58.7% and 10 year survival of 46.1% compared with 78.4% and 66.0% for women whose last childbirth was more than 2 years before their diagnosis. After adjustment for age, reproductive factors, and stage of disease (tumour size, axillary nodal status, and histological grading), a diagnosis sooner than 2 years since last childbirth was significantly associated with a poor survival (relative risk 1.58, 95% confidence interval 1.24 to 2.02) compared with women who gave birth more than 5 years previously. Further analyses showed that the effect was not modified by age at diagnosis, tumour size, and nodal status. CONCLUSIONS: A diagnosis of breast cancer less than 2 years after having given birth is associated with a particularly poor survival irrespective of the stage of disease at debut. Therefore, a recent pregnancy should be regarded as a negative prognostic factor and should be considered in counselling these patients and in the decisions regarding adjuvant treatment.

Adult↗
PubMed1997

Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial.

BACKGROUND: Irradiation after mastectomy can reduce locoregional recurrences in women with breast cancer, but whether it prolongs survival remains controversial. We conducted a randomized trial of radiotherapy after mastectomy in high-risk premenopausal women, all of whom also received adjuvant systemic chemotherapy with cyclophosphamide, methotrexate, and fluorouracil (CMF). METHODS: A total of 1708 women who had undergone mastectomy for pathological stage II or III breast cancer were randomly assigned to receive eight cycles of CMF plus irradiation of the chest wall and regional lymph nodes (852 women) or nine cycles of CMF alone (856 women). The median length of follow-up was 114 months. The end points were locoregional recurrence, distant metastases, disease-free survival, and overall survival. RESULTS: The frequency of locoregional recurrence alone or with distant metastases was 9 percent among the women who received radiotherapy plus CMF and 32 percent among those who received CMF alone (P<0.001). The probability of survival free of disease after 10 years was 48 percent among the women assigned to radiotherapy plus CMF and 34 percent among those treated only with CMF (P<0.001). Overall survival at 10 years was 54 percent among those given radiotherapy and CMF and 45 percent among those who received CMF alone (P<0.001). Multivariate analysis demonstrated that irradiation after mastectomy significantly improved disease-free survival and overall survival, irrespective of tumor size, the number of positive nodes, or the histopathological grade. CONCLUSIONS: The addition of postoperative irradiation to mastectomy and adjuvant chemotherapy reduces locoregional recurrences and prolongs survival in high-risk premenopausal women with breast cancer.

Adult↗
PubMed1997

Should women be advised against pregnancy after breast-cancer treatment?

BACKGROUND: Oestrogen is an established growth factor in breast cancer. There has, therefore, been much discussion about whether women should be advised against becoming pregnant after breast-cancer treatment because of a possible negative prognostic effect from the high oestrogen concentrations associated with pregnancy. METHODS: We studied 5725 women with primary breast cancer. Information on these women was obtained from the Danish Breast Cancer Cooperative Group. Since 1977 this group has collected population-based data on tumour characteristics, treatment regimens, and follow-up status of Danish women with breast cancer. Details of reproductive history were obtained from The Danish Civil Registration System, the National Birth Registry, and the National induced Abortion registry. We estimated the relative risk of death among women who became pregnant after breast-cancer treatment compared with women who had not become pregnant. FINDINGS: 5725 women with primary breast cancer aged 45 years of younger at the time of diagnosis were followed up for 35,067 patient-years. Among these, 173 women became pregnant after treatment of breast cancer. Women who had a full-term pregnancy after breast-cancer treatment had a non-significantly reduced risk of death (relative risk 0.55 [95% CI 0.28-1.06]) compared with women who had had no full-term pregnancy after adjustment for age at diagnosis, stage of disease (tumour size, axillary nodal status, and histological grading), and reproductive history before diagnosis. The effect was also not significantly modified by age at diagnosis, tumour size, nodal status, or reproductive history before diagnosis of breast cancer. Neither miscarriages nor induced abortions after breast-cancer treatment influenced the prognosis. INTERPRETATION: We found no evidence that a pregnancy after breast-cancer treatment increased the risk of a poor outcome.

Abortion, Induced↗
PubMed1997

Quality control of end results in a Danish adjuvant breast cancer multi-center study.

In a Danish multi-center study, quality control was performed on off-study data for high-risk breast cancer patients included in protocols of adjuvant therapy. In the two protocols 4455 patients were randomized and 2477 were registered off-study. Data from these patients were validated by reviewing the patients' records. Incorrect data were observed in 16.2% of the cases who went off-study due to recurrence, other malignant disease or death. In 258 of 2133 patients unidentical locations were demonstrated. Of these, 104 showed a time difference also. A major difference in site of recurrence was found in 107 patients (5.0%), 43 of whom were upstaged from local to a distant recurrence and 64 were downstaged. A time difference of more than 30 days was found in 192 patients (9.0%) and in 17 the difference exceeded 366 days. A time difference only was found in 88 patients (4%). The major parameter in the statistical analysis of the two protocols, i.e. recurrence-free survival, was not significantly influenced by the validation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Molecular cytogenetic analysis of a nontumorigenic human breast epithelial cell line that eventually turns tumorigenic: validation of an analytical approach combining karyotyping, comparative genomic hybridization, chromosome painting, and single-locus fluorescence in situ hybridization.

The immortalized, nontumorigenic human breast epithelial cell line HMT-3522 has been used as a model for premalignant and, eventually, malignant development. During cultivation, the karyotype evolution was followed. At an early stage, a very long constant phase showed a near-diploid karyotype, with only five marker chromosomes. DNA from this phase was used for comparative genomic hybridization (CGH) analysis, confirming a previously known MYC amplification, and the integration sites were subsequently determined by single-locus fluorescence in situ hybridization (FISH). Furthermore, gains of 5q22-qter and 20q11-qter and deletion of most of chromosome 6 (6p23-qter) were detected by CGH. Because of uncertainty about some of the indicated changes, including a deletion of Ip35-pter, the CGH findings were investigated more closely by chromosome painting, leading to a revision of the karyotype: 45,XX,del(I)(p35),-6,dup(8)(pter-->qter::qter-->q24),der(12) t(6;12)(p23; p13),der(14)t(5;14)(q22;q32.3),der(17)t(8;17;20)(17pter-->17q25 ::8qter--> 8q23::8q24-->8qter::8q24-->8qter:: 8q23-->8q24.1::20q11-->20qter). Some karyotypic changes were confirmed by CGH; others had to be revised; and, in the Ip35 region, classical cytogenetics seems superior to CGH. However, CGH revealed a karyotypically unsuspected dup(20q) that might be of special relevance to breast tumor initiation or progression. Our study confirms that CGH is supplementary to current technologies, e.g., karyotyping and Southern analysis, but cannot replace them. In addition, our cell line turned out to be an excellent model for comparison among the different methods. The results imply that future cytogenetic analyses of complex karyotypes should be based on a combination of karyotyping, CGH, and FISH.

Breast↗
PubMed1996

[Mammographic screening in the municipality of Copenhagen. Results of the first screening round].

The aim of the study was to evaluate the results from the prevalence round of the mammography screening programme in the Municipality of Copenhagen. All women who by 1 April 1991 were 50-69 years old, and who lived in the Municipality of Copenhagen, were during the period 1 April 1991-24 April 1993 offered a mammography. Those with suspect findings were recalled for further examination and possible biopsy. Women with breast cancer were offered treatment according to the standard national protocols (DBCCG). The participation rate was 71% (30,416/43,087). Among these 2043 (6.7%) were re-examined and 592 (1.9%) underwent surgical biopsy. Breast cancer was revealed in 359 (1.2%) women, of whom 88% had an invasive breast cancer. Prevalence of breast cancer increased significantly with increasing age. The positive predictive value for breast cancer among those re-examined was 18% and for those who had a surgical biopsy 61%. Among women with an invasive breast cancer 41% had a tumour of 10 mm or less, 80% had negative lymph node status and 56% had breast conserving surgery. During the following 12 months 14 women with a normal mammogram at the screening round developed breast cancer giving a sensitivity of 96%. It is concluded that the first mammography screening in Denmark showed the highest breast cancer prevalence published so far. A possible explanation could be a high sensitivity of the screening method, indicated by a relatively high frequency of small cancers. The screening programme was fully comparable with international standards.

Aged↗
PubMed1996

[Treatment of primary breast cancer. Consequences of mammographic screening in the municipality of Copenhagen].

In order to analyse changes in the pattern of primary treatment of breast cancer after introduction of mammography screening in the Copenhagen municipal area every second year, retrospective analyses of data from the Danish Breast Cancer Cooperative Group were performed. Newly diagnosed patients with breast cancer of the age of 50-69 years from the Copenhagen municipal area (1040 patients) were compared to a similar group of patients from the rest of Denmark (7353 patients). Parameters such as tumour size, lymph node status, grade of anaplasia, frequency of breast preserving surgery and adjuvant treatment were analysed. Introduction of mammography screening resulted in almost a doubling of newly diagnosed patients with invasive breast cancer during the prevalence phase, and a significant increase in the number of patients with tumour size < or = 1 cm without metastases to the axillary nodes. The frequency of breast preserving surgery increased from 5 to 45% in the municipality of Copenhagen compared to 6 to 19% in the rest of the country. Ratio between low-risk versus high-risk patients increased from 1.0 before screening to 2.7 in the following prevalence phase and 2.5 in the first year of the subsequent incidence phase, while the ratio in the rest of Denmark was the same throughout the whole study period. It can be concluded that the introduction of mammography screening resulted in significant changes in the treatment pattern of patients with primary breast cancer.

Aged↗
PubMed1996

Femoral fractures in postmenopausal breast cancer patients treated with adjuvant tamoxifen.

The anti-estrogen tamoxifen is the prevalent endocrine treatment in postmenopausal breast cancer patients. However, nothing is known about the long-term effects of the drug on the skeleton as assessed by the occurrence of fractures. We investigated the occurrence of fractures of the femur in patients from a Danish Breast Cancer Cooperative Group (DBCG) trial initiated in 1977 by a linkage of data from the Danish National Registry of Patients with data from the DBCG registry. 1716 postmenopausal women with high-risk breast cancer were randomized to local radiotherapy with or without tamoxifen, 30 mg daily for 1 year. Fifty-one patients in the control group had one femoral fracture and 64 tamoxifen treated patients had one femoral fracture. Eleven patients in the control group had one trochanteric fracture compared to 27 patients in the tamoxifen group (logrank = 5.28. P = 0.022; hazard ratio = 2.12, 95% CL 1.12, 4.01). The results could not be explained by a longer survival in the tamoxifen group nor by bone metastases with pathological fractures. In conclusion, our study suggests that tamoxifen does not seem to offer protection against fractures in old age and may even increase the risk of fractures at particular sites. This hypothesis needs to be disproved or confirmed in other trials.

Aged↗
PubMed1996

Dose-response relationship of epirubicin in the treatment of postmenopausal patients with metastatic breast cancer: a randomized study of epirubicin at four different dose levels performed by the Danish Breast Cancer Cooperative Group.

PURPOSE: To test for possible correlations between dose of single-drug epirubicin and efficacy/toxicity in postmenopausal women with metastatic breast cancer. The study also included analysis of a correlation between pharmacokinetic and pharmacodynamic parameters. PATIENTS AND METHODS: Two hundred eighty-seven women were randomized to receive either 40, 60, 90, or 135 mg/m2 of epirubicin intravenously (IV) every 3 weeks. Treatment consisted of first-line cytotoxic therapy for metastatic disease. In patients with early progressive disease after either 40 or 60 mg/m2, dose escalation to 135 mg/m2 was performed. A full pharmacokinetic analysis was performed in 78 patients. RESULTS: Among 263 eligible patients, an increase in response rate and time to progression was found with an increase in dose from 40 to 90 mg/m2, while no increase in efficacy was found from 90 to 135 mg/m2. Multivariate analysis, using the Cox proportional hazards model with time to progression as the end point, confirmed that epirubicin dose more than 60 mg/m2 was an independent prognostic covariate. Furthermore, a significant association was established between randomized dose and both hematologic and nonhematologic toxicity. No association between pharmacokinetic parameters and efficacy parameters was demonstrated. On the other hand, a significant correlation between pharmacokinetic parameters and both hematologic and nonhematologic toxicity was found. CONCLUSION: An increase in dose of epirubicin from 40 to 90 mg/m2 is accompanied by increased efficacy. Further increases in dose do not yield increased efficacy. A positive correlation between epirubicin dose and toxicity, as well as a correlation between pharmacokinetic parameters and toxicity, was also established.

Adult↗
PubMed1995

[Menstrual cycle and surgery of breast cancer. Point of time for the surgery of primary breast cancer in connection with menstrual cycle is without prognostic significance].

From 1977 to 1989 6488 patients under fifty years with primary breast cancer were registered in the nationwide Danish Breast Cancer Cooperative Group (DBCG). Among these information on last menstrual period prior to surgery was available in 1635 cases which constitute the study group of the present analysis. The group was representative of the total group with regard to prognostic factors and survival. In the study group time of surgery in relation to last menstrual period was found to have no influence on five- and ten year survival.

Adult↗
PubMed1995

[Significance for prognosis of delayed diagnosis and treatment of breast cancer].

In a study of 7608 patients with primary breast cancer the effect of patient's and doctor's delay on survival was examined. The delay was arbitrarily divided into the following intervals: Short (0-14 days), intermediate (15-60 days) and long (> 60 days). The delay had significant influence on survival. A long patient's delay was associated with an unfavourable outcome, as compared with a short delay. On the contrary, the prognosis was better for patients with a long doctor's delay compared to that of a short doctor's delay. Overall, when corrected for age, the prognostic value of delay in terms of mortality increased by 24% for a long patient's delay compared to a short one, and by 13% for a short doctor's delay compared to a long one. This suggests that all causes of delay should be kept at a minimum.

Adult↗
PubMed1995

Medullary carcinoma of the breast. Prevalence and prognostic importance of classical risk factors in breast cancer.

In an earlier study of 235 breast cancers with medullary features, we concluded from a multivariate Cox regression analysis that only four histopathological features contained significantly positive prognostic information. In the present study, continuing our work on the same population base, we used these histological characteristics (predominantly syncytial growth pattern, no tubular component, diffuse stromal infiltration with mononuclear cells and sparse necrosis (< 25%), as diagnostic criteria for medullary carcinoma of the breast (MC). We found a significantly better prognosis for patients with MC than those with non-medullary carcinoma (NMC) or infiltrating ductal carcinoma (IDC). All tumours in the MC group were grade II or III (96% grade III). A significantly different distribution of general risk factors such as lymph node status, invasion, steroid receptor status, and menopausal status, was found between the group of MC and the control group of IDC grades II + III. Further, general risk factors, which are found to be of major prognostic importance in IDC, had little prognostic impact in MC. We found MC to be biologically unique, and patients with MC have a better than average prognosis compared to that of IDC. We propose a new histological definition of MC, but stress that prospective studies have to be performed.

Breast Neoplasms↗