High dose mitoxantrone with thiotepa, cyclophosphamide and autologous stem cell rescue for high risk stage II and stage III breast cancer. German GABG-4/EH-93-Study.
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Adult↗
Biomedical subjects
W Jonat
Publications and source records attributed to W Jonat.
Transforming growth factor beta 2 (TGF-beta 2) levels in plasma of patients with metastatic breast cancer treated with tamoxifen.
Blood levels of transforming growth factor beta 2 (TGF-beta 2) were measured in 20 patients with metastatic breast cancer before and during treatment with the antiestrogen tamoxifen, and in a control group of 7 patients with primary breast cancer before and during adjuvant tamoxifen treatment. The results of this study reveal typical time patterns for TGF-beta 2 in relation to the clinical outcome. Patients in remission showed a significant increase of TGF-beta 2 in the first 4-6 weeks of therapy, followed by a subsequent decrease. Patients who did not respond showed unchanged or diminished TGF-beta 2 values after start of therapy, followed by a later increase preceding the clinical manifestation of tumor progression. Thus, TGF-beta 2 blood levels after 4 weeks of tamoxifen treatment can be used as an early marker for prediction of response.
Breast Neoplasms↗
[Chemotherapy and hormone therapy in breast carcinoma].
Both chemotherapy and hormonal therapy have been used in the adjuvant therapy of breast cancer to treat micrometastatic disease before it is clinically detectable. Several prospective, randomized trials consistently have demonstrated that disease-free survival can be significantly prolonged by the use of adjuvant chemotherapy. In some of these trials overall survival was increased as well. Premenopausal nodal-positive patients should receive adjuvant chemotherapy e.g. six cycles of CMF. Tamoxifen reduces overall tumor recurrence and mortality in postmenopausal estrogen receptor positive patients and to a lesser extent in estrogen receptor poor or negative patients. The effect of GnRh-analog for premenopausal patients with is currently investigated in multicentric studies. A response related strategy for management of metastatic breast cancer by hormonal manipulation and cytotoxic chemotherapy is outlined.
Antineoplastic Combined Chemotherapy Protocols↗
A randomised study to compare the effect of the luteinising hormone releasing hormone (LHRH) analogue goserelin with or without tamoxifen in pre- and perimenopausal patients with advanced breast cancer.
The use of goserelin with or without tamoxifen was investigated in a randomised multicentre study involving 318 pre- and perimenopausal advanced breast cancer patients. With a median follow-up of 93 weeks, 31% of goserelin-treated patients had objective responses (UICC criteria) compared with 38% of goserelin plus tamoxifen-treated patients (P = 0.24). There was a modest benefit in favour of combination therapy in time to progression (P = 0.03) but not in survival (P = 0.25). Median follow-up for survival was 117.5 weeks. Median times for disease progression and survival were 23 and 127 weeks in the goserelin alone group and 28 and 140 weeks in the combination group, respectively. In 115 patients with skeletal metastases only, significant differences in favour of combination therapy were seen in response rate, time to progression and survival. Both treatments were well tolerated and no additional safety issues were associated with combination therapy.
Adult↗
[Primary lymphoma of the cervix uteri--2 case reports].
Two cases of primary non-Hodgkin's lymphoma of the uterine cervix are described. Diagnostic pitfalls and therapeutic applications of this rare disease are discussed. The main approach in local therapy is external beam radiation--with or without surgical staging. Prognosis is favourable--depending on the stage of disease.
Adult↗
[Flow cytometry detected S-phase fraction and ploidy as prognostic parameters in primary, node-negative breast cancer].
100 specimens of patients with primary node-negative breast cancer were examined by flow cytometry. 64 tumours were shown to be diploid and 36 tumours were aneuploid. The median was the cut-off level for tumours with low S-phase (< or = 10.9%) and high S-phase values (> 10.9%). Aneuploid tumours were associated with high S-phase fraction. The average length of follow-up was 42 months. In univariate analysis for disease-free survival, diploid tumours were shown to have a slightly better prognosis than aneuploid tumours (p = 0.07). This trend could not be shown in multivariate analysis. The S-phase fraction proved to be an independent prognostic factor. Patients, whose tumours had S-phase fractions < or = 10.9%, had significantly longer disease-free survival in univariate (long-rank-test: p = 0.021), as well as in multivariate analysis according to the Cox regression model (p = 0.033). Since, as already stated, the S-phase fraction is an independent prognostic factor for node-negative breast cancer, further adjuvant therapy studies should take this factor into consideration.
Adult↗
Formestane in the treatment of advanced postmenopausal breast cancer.
In a phase II study, 91 women with advanced breast cancer received formestane (Lentaron) 500 mg intramuscularly every 2 weeks for 6 weeks, and then 250 mg every 2 weeks thereafter; all were either postmenopausal or surgically oophorectomized, and most had received previous hormonal treatment and/or chemotherapy. Complete or partial response was seen in 23%, disease stabilization in 29%. Disease-free interval and site of metastatic lesions did not significantly affect response. Patients who had previously responded to tamoxifen showed the best results with formestane. Side effects were generally mild and transient; only 3 patients had to discontinue treatment. Serum estradiol and estrone levels fell significantly after 2 weeks' treatment, and remained suppressed; there were no significant changes in serum cortisol, blood parameters, and liver and kidney function. Formestane thus appears to be an effective, specific and well-tolerated aromatase inhibitor for the treatment of advanced postmenopausal breast cancer.
Adult↗
[Prognostic factors in breast cancer].
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Biomarkers, Tumor↗
Overexpression of p53 and prognosis in breast cancer.
BACKGROUND: Assessment of prognostic markers in breast cancer independent of the axillary lymph node status is of major concern for the application of adjuvant treatment regimens. The current treatment decision is based mainly on the axillary lymph node status. Because of improved screening methods, the number and proportion of patients with node-negative disease are increasing, which warrants a search for reliable prognostic parameters. The application of tumor suppressor gene expression appears to be especially suited as a marker of the progress in malignant cellular dedifferentiation. METHODS: Tumor tissues of 156 patients with primary invasive breast cancer were analyzed immunohistochemically for the presence of p53 protein in paraffin-embedded material. The reaction to monoclonal antibody PAb1801 yielded better results than did reactions to monoclonal antibody DO1 and polyclonal antibody CM-1. The significance of the immunohistochemical data was compared with a panel of established risk factors. RESULTS: Nuclear accumulation of p53 protein proved to be an independent marker of dedifferentiation, regardless of the lymph node status. Tumors showing p53 immunoreactivity were significantly more often related with histological Grade 3 and the absence of steroid hormone receptors. Kaplan-Meier estimation and multivariate analysis of disease-free and overall survival rate corroborated the importance of p53 as a prognostic parameter. CONCLUSION: Overexpression of p53 protein emerged as a reliable and independent predictor for disease recurrence and reduced survival rates in patients with breast cancer.
Adult↗
Human breast cancer: frequent p53 allele loss and protein overexpression.
A sample of 114 primary breast tumors and corresponding constitutional DNA were tested for loss of heterozygosity (LOH) of the YNZ22 and p53 genes, both located in the 17p13 region. Loss of the p53 allele was found in 28 of 44 primary breast carcinomas (64%). In contrast LOH in only 26 of 61 tumors (43%) was detected with the variable number of tandem repeats (VNTR) probe YNZ22 mapping at 17p13.3 close to the p53 locus at 17p13.1. Among 19 tumors informative for both probes allele loss at 17p13.3 never occurred without p53 involvement. These data suggest, that p53 is the target of 17p13 allelic deletions in human breast cancer. Immunohistochemistry showed overexpression of the p53 protein in 25 of 50 cases (50%) presumably reflecting activating point mutations. Overexpression was not correlated with allele loss but seemed to be closely related to the presence of point mutations in this study. No homozygous deletions or rearrangements of the p53 gene were detected. This would argue for an important role of heterozygous p53 mutations in human breast cancer.
Alleles↗
Survival data relating to the use of goserelin depot in the treatment of premenopausal advanced breast cancer.
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Breast Neoplasms↗
[Immunohistochemical detection of EGF-receptors in breast cancers].
We examined the possibility of a quick and easy-to-perform way to determine the EGF receptor status in primary breast cancer cells by immunohistochemical staining. For this, we used two different monoclonal antibodies on corresponding tissue slides (Gullick, London; Mendelsohn, New York). The staining was interpreted by a semiquantitative histoscore. With both antibodies, we were able to detect EGF-R in breast tumours. We examined 80 tumours. 15 respectively 21% were EGF-R rich. 25% of the tumours were classified EGF-R poor. In 64 (54%) we were not able to detect EGF-R. The judgement of the EGF-R status by the different antibodies was identical in 80%. The results were also compared with the oestrogen receptor status (ER). We did not find a significant accumulation of EGF-R positive tissues in the group of ER-negative tumours (11/28 respectively 16/32). Nevertheless most ER-positive tumours showed a negative EGF-R receptor score (32/52; 27/48). These results are comparable to the studies of the Sainsbury group. In addition we compared the EGF-R of our tumours also with other parameters for the prognosis of breast cancer such as lymph node status, histological grading and menopausal status. We found, that nearly two thirds of the EGF-R negative tumours were lymph node negative. Only 18% of the lymph node negative tumours had a positive EGF-R status in both techniques. The results of immunohistochemical staining were also compared with a radio-receptor assay. The results were identical in 85% of the cases.
Adult↗
Randomized phase II study of single-agent epirubicin +/- verapamil in patients with advanced metastatic breast cancer. An AIO clinical trial. Arbeitsgemeinschaft Internistische Onkologie of the German Cancer Society.
BACKGROUND: Anthracyclines are the most active cytostatic agents in patients with metastatic breast cancer. Drug resistance and dose intensity are relevant issues in the treatment of cancer. METHODS: A randomized phase II study in 51 patients with advanced progressive metastatic breast cancer was performed. Twenty-six were treated with epirubicin (EPI) 120 mg/m2 i.v. bolus injection divided over three days combined with a daily dose of 480 mg verapamil (VPL) orally administered one day before and during EPI. Twenty-five patients received the same dose and schedule of EPI without VPL. Evaluation of response was carried out after three 21-day cycles. Study endpoints were objective response rate and overall survival. RESULTS: Among the 24 evaluable patients treated with EPI+VPL 1 CR (4%), 7 PR (29%), 9 NC (38%) and 7 PD (29%) were observed. Two patients were excluded because of toxicity. Among the 24 evaluable patients treated with EPI alone 8 PR (28%), 6 NC (24%) and 10 PD (40%) were observed, and one patient was excluded because of toxicity. Myelotoxicity was the major side effect followed by alopecia, stomatitis/mucositis and nausea. The patient group treated with VPL had lower blood pressure levels during therapy, with complete normalization after discontinuation of VPL. The median overall survival times were similar: 7.4 month in the EPI group and 8.9 month in the EPI+VPL group. CONCLUSION: In both treatment groups the objective response rate was about 30% and the overall survival rates were also the same. No clinical relevance could be demonstrated for the hypothesized resistance modifying action of VPL. Furthermore, VPL did not increase the toxicity of EPI.
Adult↗
Adjuvant randomized trials of doxorubicin/cyclophosphamide versus doxorubicin/cyclophosphamide/tamoxifen and CMF chemotherapy versus tamoxifen in women with node-positive breast cancer.
PURPOSE: We report two randomized trials of adjuvant systemic therapy in 747 patients < or = 65 years of age with histologically proven node-positive breast cancer. PATIENTS AND METHODS: Patients were selected for the two trials on the basis of lymph node and hormone receptor status. The only stratification was based on the treating institution. In patients with a lower probability of recurrence (n = 276), a comparison between endocrine therapy (tamoxifen [Tam] 30 mg/d for 2 years) and chemotherapy (cyclophosphamide, methotrexate, and fluorouracil [CMF] intravenously [IV], six cycles every 4 weeks) was performed. In patients with a higher risk of recurrence (n = 471), a comparison between chemotherapy alone (doxorubicin plus cyclophosphamide [AC] i.v., eight cycles every 3 weeks) and the same chemotherapy plus Tam was made. RESULTS: Overall, we found that CMF and Tam are equally effective in a subgroup of patients with a relatively good prognosis (low-risk patients). However, in the subset of women < or = 49 years old, a significantly greater disease-free survival (DFS) rate (P = .01) and overall survival (OS) rate (P = .002) was observed following therapy with CMF compared with Tam. In patients > or = 50 years old, the opposite was found, and Tam appeared to be superior to CMF (DFS, P = .003; OSm P = .5). These results must be interpreted cautiously, since a post-hoc stratification of patients by age (< or = 49, > or = 50) was performed, and significantly more younger, low-risk patients were randomized to receive chemotherapy alone and more older patients to receive Tam alone. Among patients with a relatively poor prognosis (high-risk patients), a combination of AC plus Tam was equivalent to AC and, when women were analyzed by age, this was found to be true of patients < or = 49 years as well. However, the addition of Tam to AC in women age > or 50 years resulted in a statistically significantly higher DFS (P = .01) and a trend toward better OS compared with women who received AC alone. CONCLUSION: Further trials are required to analyze the role of combined simultaneous or sequential chemoendocrine adjuvant treatment or each single therapy alone in defined risk-adapted subsets of node-negative and node-positive patients.
Antineoplastic Combined Chemotherapy Protocols↗
[Therapy of metastatic breast cancer].
Metastatic breast cancer is incurable, However, the use of different therapeutic modalities like endocrine therapy, chemotherapy, surgery and radiotherapy can effectively palliate symptoms and, under the best of circumstances, prolong life. When systemic treatment is indicated, endocrine therapy should be used first in most cases. This is especially true for estrogen- and progesterone-receptor-positive tumors with relative good prognosis. If one endocrine therapy is effective, there is a high probability that the following endocrine steps will be effective too. Consequently, after initial response to an endocrine treatment, in case of progress, another endocrine therapy should be used. Chemotherapy is indicated in acute life-threatening disease like extensive visceral disease or if endocrine treatment was not effective. The use of surgery and radiotherapy as local therapies should always be considered, if metastasis is limited to only one site (not liver metastasis) or in cases of impending complications like pathological bone fractures.
Antineoplastic Combined Chemotherapy Protocols↗
Goserelin depot in the treatment of premenopausal advanced breast cancer.
333 pre- and peri-menopausal patients with breast cancer entered a programme of open studies on the effect of goserelin. Of the 333 patients, 265 patients were entered into assessable efficacy studies. Efficacy data were analysed from 228 eligible patients receiving 3.6 mg of goserelin administered as a subcutaneous injection of a depot formulation once every 28 days. Mean serum luteinising hormone (LH) and oestradiol concentrations were suppressed by day 22 after the first injection. Subjective response occurred in 68.3% of patients assessed. Objective response (UICC criteria) occurred in 36.4% of patients and the lifetable median duration of response was 44 weeks. Responses were observed in all histological grades of tumour, and regardless of oestrogen receptor status. Treatment was well tolerated with no withdrawals due to possible adverse reactions of which hot flushes (75.9%) and loss of libido (47.4%) were commonly encountered. Goserelin provides an effective well tolerated medical alternative to ovarian ablation in the management of advanced breast cancer.
Adult↗
[Follow-up of 551 patients with node-negative breast cancer].
To evaluate the prognostic significance of established clinical, histological, and biochemical factors, we examined the survival data of 551 node-negative breast cancer patients. At a median follow-up of 5 years, we found 114 recurrences, 79 of them at distant sites. 41 patients died. 84 patients with less than 8 examined lymph nodes, adjuvant systemic treatment, or treatment differing from standard procedures, had a statistically significant shorter overall survival and were excluded from further analysis. With regard to relapse-free and overall survival univariate and multivariate analyses of the remaining 467 patients revealed only few factors with prognostic significance. In multivariate analysis of overall survival by the Cox regression model, statistically significant prognostic value was limited to three factors: lymphangiosis carcinomatosa (relative risk 4.8, 95%-confidence interval 2.0-11.7), postmenopausal status (0.38, 0.17-0.84), and positive progesterone receptor status (0.37, 0.14-1.0). In addition, there was a trend (p = 0.075) of prolonged survival in patients with Bloom and Richardson grade I cancers. The few prognostic factors found were able to identify patients with very good, as well as very bad prognosis. However, for the majority of node-negative breast cancer patients, estimation of prognosis remains unsatisfactory. Therefore, further independent prognostic factors are necessary.
Actuarial Analysis↗