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Biomedical subjects

W Jonat

Publications and source records attributed to W Jonat.

At least 91 records · Page 5Linked to original sources
PubMed1991

[Special clinical and follow-up aspects of invasive lobular breast cancer].

We examined 121 invasive lobular breast carcinomas (ILCs) with regard to certain standardised prognosis parameters, such as tumour size, receptor status, histological grading, the presence of lymphangiosis carcinomatosa, and the histological nodal status of the axillae and correlated these findings with follow-up data obtained over a mean period of 65 months. The parameters, tumour size, presence of lymphangiosis carcinomatosa, and nodal status, were found to be correlated and to have a significant influence on the patients' overall survival time, but not on relapse-free survival. Receptor status appeared to have no significant influence on patient survival. However, the incidence of death, owing to tumour-related causes, was higher among patients with receptor-negative tumours than amongst those with receptor-positive carcinomas. In contrast, the histological grading of a tumour appeared to exercise no effect on tumour prognosis. At 30%, the rate of local tumour recurrence at the primary site was markedly higher than for other histological types of breast carcinoma. In nearly one-half (45%) of such relapses, however, further tumour progression did not occur. Most tumours, exhibiting only local recurrence were initially node-negative, whilst those that produced distant metastases later had usually exhibited axillary lymph node metastases at primary therapy. Bilateral carcinomas occurred more frequently (15.6%) than is the case amongst ductal carcinoma. The observed tendency amongst ILCs toward local recurrence and bilateral growth might be accounted for in terms of their high incidence of multicentral tumour growth and associated pre-invasive neoplastic alterations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

The depot GnRH analogue goserelin in the treatment of premenopausal patients with metastatic breast cancer--a 5-year experience and further endocrine therapies. Cooperative German Zoladex Study Group.

Continuous administration of gonadotrophin-releasing hormone (GnRH-)analogues leads to a receptor-down regulation of pituitary GnRH-receptors and subsequently inhibits ovarian hormone production. Since October, 1984, 118 evaluable pre- and perimenopausal patients (median age 42, range 25-55 years) with metastatic breast cancer were entered into an open phase II multicenter trial to evaluate efficacy of this new treatment modality. Patients were treated with the GnRH-analogue Goserelin (3.6 mg depot s.c. every 4 weeks) as first line therapy and followed up until progression. Mean serum gonadotrophins LH and FSH were significantly suppressed by Goserelin. Within 2-3 weeks, mean serum E2 values decreased to values seen in castrated women (less than 30 pg/ml). Overall objective response with complete and partial remissions (CR + PR) was achieved in 44.9% of patients with a median time to progression (mTTP) of 59 weeks, (range 20-163 weeks), no change (NC) in 28.0% with a mTPP of 27 weeks (range 16-101 weeks), and progression (P) in 27.1%. Responses were seen in ER-positive as well as ER-negative tumors, and in patients with different sites of metastases (locoregional, bone, visceral, multiple). The value of different prognostic factors in relation to response rates, time to progression and time to death (overall survival) is discussed. Median overall survival (time from beginning of palliative Goserelin treatment to death) was 148 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Immunohistochemical evidence of estrogen and progesterone receptors in the female lower urinary tract and comparison with the vagina.

Tissue biopsies from the lower urinary tract and the vagina were obtained from 51 and 45 women, respectively, during incontinence surgery or other gynecological operation procedures in order to calculate hormone receptor content. We compared the results between premenopausal, postmenopausal patients with and those without hormonal treatment. Utilizing the enzyme immunohistochemical assay we were able to demonstrate nuclear estrogen and progesterone receptors in the smooth muscle of the trigone and the posterior part of the bladder neck. But only in about 50% of the patients receptor proteins were detected in the frozen thin sections of these tissues. Biopsies from the anterior part of the bladder neck and the bladder vault were never receptor positive. In the vagina the rate of receptor-positive tissues was about 80%; in comparison, a smaller number of patients had receptor-positive cells in the bladder. From 29 patients we obtained specimens from the trigone and the vagina as well. The correlation of receptor-positive and -negative tissues of both organs was only 66%. Thus tissue biopsies obtained from the vagina only are not sufficient to discuss the probability of hormonal influence of the lower urinary tract.

Biopsy↗
PubMed1990

A phase II study of intensive-dose epirubicin/verapamil as induction therapy followed by intensive-dose ifosfamide for advanced breast cancer.

Preliminary data of an ongoing phase II-study in metastatic breast cancer patients are presented. Patients with metastatic breast cancer entered the study after hormone therapy had failed; prior treatment with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) was also allowed. The patients were treated with three cycles of 40 mg/m2 epirubicin i.v. on days 1-3 and 4 x 120 mg oral verapamil on days 0-3, given every 3-4 weeks. After three chemotherapy courses, ifosfamide was given as a short infusion of 3 g/m2 on days 1-3. Mesna (20% of the total ifosfamide dose) was given 0, 4 and 8 h after ifosfamide administration. Response was evaluated after three cycles of epirubicin/verapamil and after the last (third) cycle of ifosfamide. The side effects of this treatment were tolerable. The epirubicin/verapamil combination was no more toxic than epirubicin alone. Despite the high dose of verapamil, systolic blood pressure remained above 80 mm Hg, and patients never had a period of strict bed rest. Alopecia was almost complete after induction therapy with epirubicin/verapamil, and nausea and vomiting were absent or mild during epirubicin/verapamil chemotherapy and were easily controlled by antiemetics during ifosfamide treatment. Stomatitis and mucositis, the main toxic effects, could be ameliorated by intensive mouth-washing procedures. The haematological toxicity was greater after epirubicin/verapamil treatment than after ifosfamide therapy, but neither bleeding nor infections due to thrombocytopenia or leucopenia were observed.

Adult↗
PubMed1990

Aromatase inhibition with 4-hydroxyandrostenedione in the treatment of postmenopausal patients with advanced breast cancer: a phase II study.

Estrogen deprivation by aromatase inhibition is an effective treatment in breast cancer. Between October 1986 and March 1988, 91 postmenopausal patients with advanced breast cancer entered a phase II study performed jointly in three center to investigate the new aromatase inhibitor 4-hydroxyandrostenedione. Patients received 500 mg 4-hydroxyandrostenedione intramuscularly (IM) every 2 weeks for 6 weeks, and 250 mg every 2 weeks thereafter. There were two complete (CRs) and 19 partial remissions (PRs) (response rate, 23%). Disease stabilization (no change; NC) was seen in 26 patients, and in 44 patients (48%), disease progression occurred. Duration of the CRs is 20+ months, median durations of PR and NC are 13+ and 8 months, respectively. Receptor status, relapse-free interval, and sites of metastatic lesions did not appear to influence treatment results. However, efficacy of previous tamoxifen treatment favorably predicted response to 4-hydroxyandrostenedione. Serum estradiol levels decreased significantly in patients after 2 weeks of treatment. Side effects were mostly nonspecific and of low degree, requiring discontinuation of treatment in only 3% of the patients. We conclude that aromatase inhibition with 4-hydroxyandrostenedione is efficacious in the treatment of postmenopausal breast cancer.

Adult↗
PubMed1989

Effect of continuous vs intermittent application of 3-OH-tamoxifen or tamoxifen on the proliferation of the human breast cancer cell line MCF-7 M1.

The antiproliferative potency of 5 x 10(-7) M tamoxifen (TAM) and 3-hydroxytamoxifen (3-OH-TAM) was investigated during continuous (8 days) or intermittent (2 h every 2nd or 3rd day, respectively) application to the oestrogen-receptor-positive, estradiol-sensitive human mammary carcinoma cell line MCF-7 M1, a variant of MCF-7 wild type. Growth modulation was evaluated in parallel by counting cells and by measuring DNA content. Continuous incubation resulted in a growth inhibition to 21.8 +/- 3.2% by 3-OH-TAM and to 39.5 +/- 4.8% by TAM when compared with control cultures defined as 100%. Intermittent addition induced a growth reduction to 23.0 +/- 2.1% by 3-OH-TAM and to 41.2 +/- 2.4% by TAM in relation to 100% controls. Addition of 3-OH-TAM for 2 h only at day 1 resulted in an inhibition to 70.3 +/- 3.2%, again in relation to 100% controls. When TAM was administered once for 2 h at day 1 it induced an inhibition to 79.0 +/- 4.9% at day 8. The in vitro results indicate that (a) at 5 x 10(-7) M 3-OH-TAM has a better antiproliferative effectiveness than TAM, (b) the intermittent application is as effective as continuous application (no significant difference), and (c) the addition once a week reveals only a slight growth reduction after 8 days of culture. Application of the long-living TAM results in continuously high serum concentrations, which have been shown to create resistant cell clones. Compared to TAM the 3-OH metabolite has a considerably shorter half-life and its application in vivo reveals rise and fall of its serum concentrations. Since the presented data demonstrate that 3-OH-TAM is more potent than TAM and that the intermittent application is as effective as the continuous form, interval therapy with 3-OH-TAM may slow down the process of acquiring resistance to antioestrogens.

Breast Neoplasms↗
PubMed1989

LHRH analogues in early breast cancer.

A steering group has devised a protocol to compare relapse-free survival rates between women under 50 with stage II cancer, given CMF or Zoladex as adjuvant therapy. The design of the trial is discussed.

Adult↗
PubMed1989

Goserelin, a depot gonadotrophin-releasing hormone agonist in the treatment of premenopausal patients with metastatic breast cancer. German Zoladex Trial Group.

One hundred thirty-four pre- and perimenopausal patients presenting with metastatic breast cancer (median age, 42 years; range, 25 to 55) were treated with goserelin (Zoladex [ICI 118 630]; ICI Pharma, Plankstadt, Germany) a long-acting gonadotrophin-releasing hormone (GnRH)-analogue depot formulation, injected subcutaneously every 4 weeks, as a first-line therapy. One hundred eighteen patients were evaluable for response. Serum concentrations of estradiol, luteinizing hormones (LH), and follicle-stimulating hormones were significantly suppressed by Zoladex. Mean serum estradiol values fell into the range of castrated or postmenopausal women within 2 to 3 weeks of therapy. This suppression was maintained for the duration of therapy. Overall objective response was: 12 (10.2%) complete remission; 41 (34.7%) partial remission; 33 (28.0%) no change; and 32 (27.1%) progression. In responders, the median time to response was 4 months (range, 2 to 11 months), median duration of response was 8 + months (range 2 to 24 months), and median time to progression was 11 + months (range, 5 to 30 months). Objective responses were seen for different sites of metastases: loco-regional (62.5%), bone (46.7%), visceral (45.0%), and multiple (35.1%). Tumor remission was more common in patients in which the primary tumor was estrogen receptor (ER)-positive (49.3%) or ER-unknown (44.0%), but appreciable response rates were also observed in ER-poor patients (33.3%). Zoladex depot was well tolerated both locally and systemically. It produced effective castration and the objective response rates and duration of remission are at least comparable to those seen following oophorectomy; however, the side effects are less. The use of depot Zoladex avoids the psychological trauma and operative morbidity of the irreversible operative castration.

Adult↗
PubMed1987

The present status of the adjuvant endocrine treatment.

Adjuvant therapy of breast cancer is accepted as a useful method for reducing mortality in patients with histologically axillary involved lymph nodes. Polychemotherapy regimens and hormonal treatment procedures are used to reach this goal. Hormonal treatment seems to be useful especially in selected patients. This article deals with (a) new methods for selecting hormone-responsive tumors and patients, and (b) it will give a brief overview of major publications concerning adjuvant endocrine therapy and (c) will summarize the data from the Gynecological Adjuvant Breast Group (GABG) trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

[Endocrine therapy of breast cancer].

A survey is given about the value of endocrine especially adjuvant treatment of breast cancer, the necessary case selection procedure with aid of time- and therapy dependent hormonal receptor status using new introduced monoclonal antibodies and of the practical possibilities. Special attention was directed to the very potent substances with less side effects aminoglutethimide, tamoxifen and high dose medroxyprogesteronacetate.

Aminoglutethimide↗
PubMed1986

Immunohistochemical measurement of estrogen receptors in breast cancer tissue samples.

A new estrogen receptor immunocytochemical assay (ER-ICA) which uses monoclonal antibodies to the estrogen receptor protein was applied to 97 breast cancer tissues. The results were correlated to those obtained by conventional dextran coated charcoal assays. The presence or absence of nuclear staining was significantly associated with positive or negative estrogen receptor status by dextran-coated charcoal (P less than 0.001). Furthermore ER-ICA results showed a high degree of correlation with a light microscopic grading. The relationship between ER-ICA results and response to endocrine therapies in patients with advanced disease was assessed in 20 patients. Six of 11 (55%) ER-ICA positive patients responded, whereas 8 of 9 (89%) ER-ICA negative patients failed.

Antibodies, Monoclonal↗