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Biomedical subjects

C Rose

Publications and source records attributed to C Rose.

At least 19 recordsLinked to original sources
PubMed1992

Adjuvant radiotherapy and risk of contralateral breast cancer.

BACKGROUND: The risk of contralateral breast cancer is increased twofold to fivefold for breast cancer patients. A registry-based cohort study in Denmark suggested that radiation treatment of the first breast cancer might increase the risk for contralateral breast cancer among 10-year survivors. PURPOSE: Our goal was to assess the role of radiation in the development of contralateral breast cancer. METHODS: A nested case-control study was conducted in a cohort of 56,540 women in Denmark diagnosed with invasive breast cancer from 1943 through 1978. Case patients were 529 women who developed contralateral breast cancer 8 or more years after first diagnosis. Controls were women with breast cancer who did not develop contralateral breast cancer. One control was matched to each case patient on the basis of age, calendar year of initial breast cancer diagnosis, and survival time. Radiation dose to the contralateral breast was estimated for each patient on the basis of radiation measurements and abstracted treatment information. The anatomical position of each breast cancer was also abstracted from medical records. RESULTS: Radiotherapy had been administered to 82.4% of case patients and controls, and the mean radiation dose to the contralateral breast was estimated to be 2.51 Gy. Radiotherapy did not increase the overall risk of contralateral breast cancer (relative risk = 1.04; 95% confidence interval = 0.74-1.46), and there was no evidence that risk varied with radiation dose, time since exposure, or age at exposure. The second tumors in case patients were evenly distributed in the medial, lateral, and central portions of the breast, a finding that argues against a causal role of radiotherapy in tumorigenesis. CONCLUSIONS: The majority of women in our series were perimenopausal or postmenopausal (53% total versus 38% premenopausal and 9% of unknown status) and received radiotherapy at an age when the breast tissue appears least susceptible to the carcinogenic effects of radiation. Based on a dose of 2.51 Gy and estimates of radiation risk from other studies, a relative risk of only 1.18 would have been expected for a population of women exposed at an average age of 51 years. Thus, our data provide additional evidence that there is little if any risk of radiation-induced breast cancer associated with exposure of breast tissue to low-dose radiation (e.g., from mammographic x rays or adjuvant radiotherapy) in later life.

Adult↗
PubMed1992

Factors influencing women to undergo screening mammography.

Despite the fact that mammography is a valuable tool for early detection of breast cancer, the majority of age-eligible American women do not avail themselves of screening mammography. To better understand why women do or do not undergo mammography and to further develop guidelines for promoting breast cancer screening, the authors investigated what impact personal factors, attitudes, and health-related behaviors have on compliance with screening mammography by surveying 521 women for information related to health behavior, health concerns, sense of well-being, satisfaction with health care, and knowledge about breast cancer. Women who underwent mammography were more likely to have a regular physician, to practice breast self-examination, to be less concerned over the cost of mammography, to be generally satisfied with their health care, to believe they have a greater sense of control over their health, and to be more knowledgeable about mammography and breast cancer. Age, health behavior, sense of well-being, locus of control, and breast cancer experience helped differentiate between women who had undergone mammography and those who had not.

Adult↗
PubMed1992

Cytotoxic treatment of metastatic breast cancer. Which drugs and drug combinations to use?

Although the optimal efficacy of cytotoxic therapy plateaued in the 1970s, no consensus yet exists regarding which cytotoxic combination to offer as first-line therapy for metastatic breast cancer. Comparison of a combination of CAF/CEF with other cytotoxic combinations reveals that an anthracycline-containing regimen not only increases response rate, but also improves time to progression and survival. Regarding appropriate duration of cytotoxic therapy, randomized trials indicate that therapy in excess of 6 months is beneficial. Although the main objective of cytotoxic therapy in patients with metastatic disease is to palliate symptoms at the least toxic cost, the finding that adjuvant cytotoxic therapy improves survival provides a clinical and ethical rational for continued research into new drugs and combinations in the hope that new strategies can be employed not only against metastatic breast cancer but may be applied with benefit also in the adjuvant situation.

Antineoplastic Agents↗
PubMed1992

Weekly oral idarubicin in advanced prostatic cancer. A phase II study.

Twenty-five patients with advanced prostatic cancer progressing after one course of endocrine treatment entered a phase II study of weekly administration of 30 mg Idarubicin orally. Twenty-two patients were evaluable for response and partial response (PR) was noted in 2 patients and stable disease (NC) in 10 patients. Median survival was 31 weeks and median time to progression was 14 weeks. Twenty-three patients were eligible in a score system combining analgetic consumption and pain reduction measured on a Visual Analogue Scale (VAS) and 30% achieved a subjective response. Fifteen patients fulfilled treatment with the planned dose and 10 patients had dose reduction to a median of 23.8 mg Idarubicin. Haematological toxicity was greater than or equal to grade 3 (WHO) in 20% of the patients. Non-haematological toxicity was dominated by nausea/vomiting with 48% grade 3 (WHO). In conclusion, Idarubicin seems of limited value in the treatment of patients refractory to first line endocrine treatment.

Administration, Oral↗
PubMed1992

Danish randomized trial comparing breast conservation therapy with mastectomy: six years of life-table analysis. Danish Breast Cancer Cooperative Group.

The Danish Breast Cancer Cooperative Group (DBCG) conducted a randomized trial comparing breast conservation with mastectomy in patients with invasive mammary carcinoma. From January 1983 to March 1989, the trial accrued a total of 1153 women. Of this number, 905 patients (79%) were randomly assigned to one of the two treatment options, whereas 248 patients (21%) did not accept randomization. Of the randomly assigned patients, 90% received the surgical option to which they had been originally assigned. In the breast conservation arm the tumor was excised with the intention of obtaining free margins determined at gross examination, and radiotherapy was subsequently administered to residual breast tissue. The axilla was dissected in all instances. Patient and tumor characteristics were similar in the two randomization arms. The median follow-up time was 40 months. At 6 years of life-table analysis the probability of recurrence-free survival was 70% in the breast conservation arm against 66% in the mastectomy arm. Survival figures were 79% against 82%, respectively.

Breast Neoplasms↗
PubMed1991

[Adjuvant endocrine treatment of postmenopausal patients with breast cancer with high risk of recurrence. 5. Results from the DBCG (Danish Breast Cancer Cooperative Group) 77C randomized trial].

The role of antiestrogen treatment of postmenopausal breast cancer patients with high risk of recurrent disease is evaluated in a nationwide, prospective trial conducted by the Danish Breast Cancer Cooperative Group (DBCG). After total mastectomy and postoperative radiotherapy (RT), 840 patients were randomized to treatment with tamoxifen (RT + TAM) for one year, and 824 were randomized to no further therapy (RT). The recurrenceree survival (RFS) after ten years of lifeable analysis is 31% in the RT + TAM treated group, and 28% in the RT group (p = 0.01). Survival is 38% and 34% in the two treatment groups, respectively (p = 0.04). The data were further analyzed with respect to prognostic factors such as age, number of positive nodes, tumour size, and degree of anaplasia. Survival is prolonged in nearly all subgroups of patients treated with RT + TAM. However, the prolongation is only significant in patients with four or more positive nodes, with tumours of less than 5 centimeters or with tumours of anaplasia grade II. Estrogen (ER) and progesterone receptor (PgR) concentrations were measured in tumours from 309 and 219 patients, respectively. Only patients with ER and PgR values above 100 fmol/mg cytosol protein seemed to have a prolongation of survival. In conclusion, a modest survival benefit is achieved with one year of adjuvant tamoxifen treatment. Nevertheless, this is the first example of a systemic treatment approach being able to change the fatal course of breast cancer in postmenopausal patients. By means of endocrine therapy, and in the context of a new randomized trial, the DBCG will try to improve the survival in these patients even further.

Aged↗
PubMed1991

[Shark liver oil (alkoxyglycerol) and cancer treatment].

Alkoxyglycerol derived from shark liver oil is marketed in Denmark and mentioned in popular articles as a supplementary agent in the treatment of cancer. A questionnaire investigation carried out in the Department of Oncology and Haematology in Odense Hospital revealed that approximately 1/3 of the patients in active neoplastic therapy employed shark liver oil preparations. The clinical investigations of alkoxyglycerol were all carried out on patients with cancer of the uterine cervix. All of the investigations were carried out by the same Swedish research group. Only a minority of the experimental material was blinded. No documentation was found for inhibited tumour growth or reduced mortality resulting from treatment with alkoxyglycerol. The number of cases of irradiation damage were found to be fewer in the groups treated with alkoxyglycerol, but the difference may be partially explained by different subdivision into stages. Alkoxyglycerol results in increase in the leukocyte and thrombocyte counts while higher or lower doses have, apparently, the opposite effect. The available literature concerning the clinical effect of alkoxyglycerol is limited and unsystematic and does not support the employment of alkocyglycerol in the treatment of cancer.

Animals↗
PubMed1991

Multiple-dose pharmacokinetics of epirubicin at four different dose levels: studies in patients with metastatic breast cancer.

Pharmacokinetic analysis of epirubicin and its metabolites epirubicinol and 7-deoxy-13-dihydro-epirubicinol aglycone during the first and the fourth courses of treatment was performed in 78 patients with metastatic breast cancer. The patients were treated every 3 weeks with epirubicin given as 10-min i.v. infusions at four different dose levels: 40, 60, 90 and 135 mg/m2. In most cases (76 of 78 cases), plasma concentration-time curves fitted to a three-compartmental pharmacokinetic model. The terminal half-life of epirubicin was independent of dose and duration of treatment. Large interindividual differences were demonstrated (mean t1/2 gamma, 21.6 +/- 7.9 h; range, 10.6-69 h; n = 110). In two subjects, extremely long half-lives and high serum bilirubin concentrations indicated impaired liver function. No correlation was found between the half-life and levels of liver alanine aminotransferase (ALAT) or serum creatinine. The metabolite epirubicinol appeared quickly after epirubicin administration and its half-lives were shorter than that of the parent compound (mean t1/2 gamma, 18.1 +/- 4.8 h; range, 8.2-38.4 h; n = 105). Formation of the aglycone metabolite was delayed and the half-life of this metabolite was shorter than that of epirubicin (mean t1/2 gamma, 13 +/- 4.6 h; range, 2.7-29 h; n = 104). The AUC of epirubicin and the total AUC (drug and metabolites) were linearly proportional to the dose, with the former value constituting two-thirds of the latter. A correlation was found between AUC and the plasma concentration of epirubicin at two time points (2 and 24 h after administration). The proposed model was AUC = 9.44 x c2 + 62.5 x c24 + 157.7 (r = 0.953).

Breast Neoplasms↗
PubMed1991

A randomized study of epirubicin at four different dose levels in advanced breast cancer. Feasibility of myelotoxicity prediction through single blood-sample measurement.

Detailed pharmacokinetic analysis and subsequent evaluation of myelotoxicity were performed in 55 patients who had been randomized to 4 different doses of epirubicin (40, 60, 90 or 135 mg/m2 given i.v. every 3 weeks). A significantly positive correlation was demonstrated between the AUC and the myelotoxicity of epirubicin. A similar correlation was observed when the metabolite epirubicinol was also considered. The decrease in leucocyte count as expressed by the logarithmic ratio between nadir WBC and initial WBC was linearly correlated with the AUC of either epirubicin alone (r = -0.55, P less than 0.001) or epirubicin and epirubicinol together (r = -0.63, P less than 0.001). As a relationship between the concentration of epirubicin in a single plasma sample taken at 6 h following i.v. administration and the AUC of the drug has been established, a log-linear relationship between the expected decrease in leucocytes and the concentration at 6 h after administration could be calculated. The proposed model is expressed as the equation: log WBCnadir = log WBCinitial -0.0073 x c6 (ng/ml)-0.14.

Bone Marrow↗
PubMed1991

Prognostic factors in adult de novo myelodysplastic syndromes treated by intensive chemotherapy.

We treated 47 adult patients with de novo myelodysplastic syndrome (MDS) by an anthracycline-AraC regimen. Median age was 54, and M/F 1.3. At diagnosis, 26 patients had refractory anaemia with an excess of blasts in transformation (RAEB-T) three had refractory anaemia (RA), 11 had refractory anaemia with excessive blasts (RAEB) and seven had chronic myelomonocytic leukaemia (CMML). Treatment was started within 3 months of diagnosis in 30 patients, and after more than 3 months in the 17 remaining patients. At the onset of treatment, 16 patients had progressed to acute myeloid leukaemia (AML). Twenty-two patients (47%) reached complete remission (CR), 10 (21%) had hypoplastic death and 15 (32%) had resistant disease. Median actuarial disease-free interval was 11 months. Median actuarial survival was 14 months from diagnosis and 10 months from the onset of treatment. A significantly higher CR rate was found in patients with RAEB-T at diagnosis (69% v 19% in patients with other FAB subtypes: P = 0.008), and in patients treated within 3 months of diagnosis. Using multivariate analysis, RAEB-T at diagnosis emerged as the most powerful prognostic factor of CR achievement. Karyotype was the only significant prognostic factor of disease-free interval, with a median of 16.5 months in patients with normal karyotype versus 4 months in patients with normal findings (P = 0.018). A subgroup of 15 patients with RAEB-T at diagnosis and normal karyotype, who had a CR rate of 80% and a median actuarial disease-free interval of 18 months, could be identified. Our results confirm that, overall, intensive chemotherapy has limited efficacy in MDS, especially when compared with allogeneic bone marrow transplantation (BMT). Relatively favourable results were obtained in our patients with RAEB-T at diagnosis, however, particularly those with normal karyotype. In that subgroup, intensive chemotherapy may be recommended, especially before BMT, as a high risk of relapse after BMT in patients with RAEB-T allografted as first line therapy has been reported.

Adolescent↗
PubMed1991

Pattern of spread and progression in relation to the characteristics of the primary tumour in human breast cancer.

Characteristics of primary breast tumours were related to the extent of dissemination, the anatomical location of metastases, and the rate of progression in 863 patients with recurrent breast cancer. The following features were examined: tumour laterality, location within the breast, size, invasion of skin or fascia, presence of residual cancer tissue (RCT) in the mastectomy specimen, and number of positive lymph nodes. Increasing tumour size, increasing number of nodes, and the presence of local invasion and RCT were all associated with a short duration of survival both from initial diagnosis and from first recurrence. None of the factors were related to either the extent of dissemination or the rate of progression. Patients who had their primary tumours located in the medial or central part of the breast had an increased incidence of mediastinal and pleural recurrences respectively. Primary tumours greater than 5 cm, invasion of skin or fascia, and presence of RCT were all associated with an increased incidence of local recurrences. In addition, both RCT and fascial invasion were associated with increased occurrence of brain metastases. Most differences were explainable on the basis of local and regional lymphodynamics. Since the status of the features examined here all vary with time from tumour inception, it is suggested that the impact on prognosis is related to variations in tumour age from inception to primary diagnosis rather than to qualitative biological differences.

Bone Neoplasms↗
PubMed1991

Estrogen receptor in primary breast cancer estimated in paraffin-embedded tissue. A study of its usefulness compared to dextran-coated charcoal assay.

Estrogen receptor (ER) was estimated immunohistochemically in formalin-fixed and paraffin-embedded tissue from the primary breast cancer in 349 postmenopausal patients with a high risk of recurrence and compared with the results of dextran-coated charcoal assay. There was a highly significant correlation between the ER classification obtained by the two methods (p less than 10(-6)). Patients ER positive according to immunohistochemical estimate had a significantly longer disease-free survival (p less than 0.001) and survival (p less than 0.001) than ER negative patients. The DCC assay showed an advantage of ER positive patients of the same magnitude. The patients, who were followed for a median of 86 months, were a subset of 1,700 patients participating in the Danish Breast Cancer Cooperative Group's randomized trial of adjuvant tamoxifen (TAM) treatment. In the presently analyzed subset of patients there were no statistically significant difference in disease-free survival (p = 0.52) or survival (p = 0.54) between patients who received adjuvant TAM and the controls. The same was true for receptor-defined subgroups regardless if the ER receptor was estimated in paraffin-embedded tissue or by the dextran-coated charcoal method. The analyzed subset might have been too small for demonstrating a positive effect of adjuvant TAM treatment.

Breast Neoplasms↗