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Biomedical subjects

L V Beex

Publications and source records attributed to L V Beex.

At least 55 records · Page 3Linked to original sources
PubMed1991

Epidermal growth factor receptor-negative tumors are predominantly confined to the subgroup of estradiol receptor-positive human primary breast cancers.

A total of 725 human primary breast tumor biopsy samples were analyzed for epidermal growth factor receptor (EGFR) content, using a multiple-point EGFR assay standardized in accordance with the recommendations of the European Organization for Research and Treatment of Cancer Receptor Study Group. After the establishment of a lower cell membrane protein threshold of 0.2 mg of membrane protein per ml of assay buffer, the results of 27% (194 samples) of the EGFR determinations were excluded from the study because of insufficient assay membrane protein content. Of the remaining 531 breast tumor biopsy samples, 57% (302 samples) were shown to be EGFR positive by Scatchard analysis, with a median value of 40 fmol/mg of membrane protein. Of the breast tumor biopsy samples, 72% (380 samples) were estrogen receptor (ER) positive, and 65% (344 samples) were progesterone receptor (PgR) positive. EGFR positivity was found in 46% (173 of 380) of ER-positive and in 85% (129 of 151) of ER-negative breast tumor biopsy samples (P less than 0.0001), as well as in 49% (168 of 344) of PgR-positive and in 72% (134 of 186) of PgR-negative breast tumor biopsy samples (P less than 0.0001). Mean EGFR levels in ER-positive breast tumor biopsy samples were lower than they were in ER-negative ones, 40 +/- 31 (SD) against 72 +/- 55 fmol/mg of membrane protein (P less than 0.0001). Similarly, mean EGFR levels in PgR-positive breast tumor biopsy samples were lower than they were in PgR-negative ones, 41 +/- 29 against 70 +/- 56 fmol/mg of membrane protein (P less than 0.0001). Both EGFR positivity and EGFR levels decreased with increasing steroid hormone receptor levels. A multivariate analysis showed only ER to be independently associated with EGFR.

Biomarkers, Tumor↗
PubMed1991

Steroid hormone receptor activity of primary human breast cancer and pattern of first metastasis. The Breast Cancer Study Group.

A series of 258 breast cancer patients with known estrogen receptor (ER) status of the primary tumour who subsequently developed metastases were reviewed for site of first metastasis. In 188 cases progesterone receptor (PgR) data were also available. Univariate analysis showed metastatic patterns to differ statistically significantly related to ER status and (less pronounced) PgR status of the primary tumour. Patients with ER-positive tumours had bone metastases three times more often than patients with ER-negative tumours. With respect to PgR-positive and PgR-negative tumours this frequency differed by a factor of two. With regard to visceral metastases ER and PgR status were equally potent prognosticators, patients with receptor negative tumours having a 50% higher frequency of visceral metastasis than patients with receptor positive tumours. Assessment of metastatic patterns in relation to combined receptor status did not substantially enhance the discriminatory value of ER and PgR when assessed separately. Multivariate analysis showed that the observed differences in metastatic patterns were all attributable to differences in the ER status of the primary tumour, and were not influenced by age, menopausal status, axillary lymph node involvement, duration of disease-free interval (DFI), mode of postoperative treatment, or the PgR status of the primary tumour.

Abdominal Neoplasms↗
PubMed1991

"Classical" CMF versus a 3-weekly intravenous CMF schedule in postmenopausal patients with advanced breast cancer. An EORTC Breast Cancer Co-operative Group Phase III Trial (10808).

The "classical" CMF (cyclophosphamide/methotrexate/5-fluorouracil) schedule was compared with a modified 3-weekly intravenous CMF schedule in postmenopausal patients with advanced breast cancer, as concern had arisen as to whether the classical schedule was the optimal way to give these drugs. The response rate with classical CMF was 48% compared with 29% for intravenous CMF (P = 0.003). Response duration was similar at 11 months, but survival longer for the classical schedule (17 versus 12 months, P = 0.016). We conclude that classical CMF is the superior regimen and attribute this to the higher dose intensity achieved.

Aged↗
PubMed1991

Favourable response of a virilizing adrenocortical carcinoma to preoperative treatment with ketoconazole and postoperative chemotherapy.

A 25-year-old woman presented with an extensive adrenocortical carcinoma with severe virilization and mild Cushing's syndrome. In the tumour there was a primacy of the P450C17 (17,20-lyase) over the P450C21 (21-hydroxylase) route, favouring the synthesis of androgens over corticoids. Preoperatively, the patient was treated with the antimycotic agent ketoconazole, a known inhibitor of steroid synthesis, at a dose of 600 mg/day and after a week 1200 mg/day, to reduce operation risks and to achieve a better metabolic control. This treatment markedly decreased hyperandrogenism and normalized the hypercortisolism. The main effect of ketoconazole was at the 17,20-lyase level and probably at a locus prior in steroidogenesis, i.e. at the P450SCC and/or 17 alpha-hydroxylase level. In contrast with other studies no effect at all was seen on the 11-hydroxylase activity of P450C11. After removal of a massive adrenal carcinoma, extending into the vena cava, vena cava resection and hemihepatectomy because of liver invasion, plasma cortisol and androgen values normalized. Despite adjuvant chemotherapy with o,p'-dichlor-diphenyl-dichloretan (4000 mg daily) hyperandrogenism soon recurred and lung metastases became manifest. Within 2 months after starting combined chemotherapy with 5-fluorouracil, cisplatin, and doxorubicin lung metastases almost completely disappeared with clinical and biochemical resolution of the hyperandrogenic state.

Adrenal Cortex Neoplasms↗
PubMed1990

Second line endocrine treatment of postmenopausal advanced breast cancer. Preliminary endocrine results of a 5-arm randomized phase II trial of medium vs low dose aminoglutethimide, with or without hydrocortisone vs hydrocortisone alone (EORTC 10861).

The supposed mechanism of action of aminoglutethimide (AG), medical adrenalectomy, has been challenged. AG is now considered to act as an inhibitor of the aromatization of mainly adrenal androgens to estrogens in peripheral tissues and/or breast cancer itself. To further establish the AG dose required to sufficiently reduce estrogen levels in plasma and the possible role of hydrocortisone (HC) in combination with AG or by itself, postmenopausal advanced breast cancer patients received AG low (125 mg bid) or medium (250 mg bid) dose alone or combined with HC (20 mg bid) or HC alone (20 mg bid). Preliminary hormonal data show a similar reduction of serum estrone and estrone sulphate by at least some 50% at 8 wk in all treatment groups. At 6 months these effects persist except for patients treated with HC alone. In the latter a normalization of estrone levels is observed with effective suppression of adrenal androgen precursors, suggesting increased aromatase activity with prolonged glucocorticoid treatment.

Aminoglutethimide↗
PubMed1990

Steroid-hormone receptors in nonpalpable and more advanced stages of breast cancer. A contribution to the biology and natural history of carcinoma of the female breast.

Tumors of five groups of patients, with (1) nonpalpable primary breast cancer, (2) palpable operable primary breast cancer, (3) loco-regionally advanced primary breast cancer, (4) first and (5) late metastatic breast cancer, were studied in respect to their steroid receptor content. A statistically significant decrease of progesterone receptor positive tumors and of tumors positive for estradiol and progesterone receptors, was found with increasing advance of the disease. A reversed extrapolation of these figures supports the hypothesis that every breast cancer contains steroid receptors and is hormone-dependent from its inception.

Biology↗
PubMed1990

[Fine-needle biopsy of cold thyroid nodules].

In retrospect we analysed 175 fine needle aspiration biopsies, performed on 154 patients with a palpable, solitary, 'cold', thyroid nodule. In contrast to conventional diagnostic methods such as ultrasound and scintigraphy fine needle aspiration is a highly specific method for the detection of thyroid cancer. We found a significant difference in the frequency of thyroid carcinoma between patients operated because of cytological diagnosis and patients operated because of clinical suspicion of cancer, 44% and 20% respectively. We conclude that fine needle aspiration is a major step forward in the evaluation of solitary thyroid nodules.

Adolescent↗
PubMed1989

Radiotherapy of choroidal metastases.

With binocular indirect ophthalmoscopy, fluorescin angiography and ultrasonography 68 choroidal metastases in 52 eyes of 39 patients were diagnosed. The primary tumors were mainly breast cancer (81%) and lung cancer (10%). After radiation treatment the visual acuity improved in 17 eyes (38%), stabilized in 15 eyes (33%), whereas in 13 eyes (29%) deterioration could not be prevented (seven eyes unknown). Regression of the lesions or its accompanying secondary retinal detachment was seen in 78% of the eyes treated. Acute transient side effects of radiation therapy were kerato-conjunctivitis (nine patients) and acute glaucoma in one patient. No cataractous changes of the lens were observed in the post radiation period (one to 42 months). Irradiation of choroidal metastases can contribute to improvement of the quality of life with a treatment scheme of 30 Gy in ten daily fractions.

Adolescent↗
PubMed1988

Adjuvant chemotherapy in premenopausal patients with primary breast cancer; relation to drug-induced amenorrhoea, age and the progesterone receptor status of the tumour.

Adjuvant chemotherapy with cyclophosphamide, 5-fluorouracil and methotrexate (CMF)-induced permanent ovarian suppression in 47 of 77 (61%) premenopausal patients with axillary node positive breast cancer. After a median observation time of 37 months the relapse-free and overall survival times were significantly longer for patients with permanent amenorrhoea. A strongly positive correlation between CMF-induced amenorrhoea and age of the patients, as well as between age and the tumour PgR status, was found. The induction of ovarian suppression predominantly occurs in patients with PgR positive tumours and may add an endocrine effect to the cytotoxic action of adjuvant chemotherapy in this particular group of older premenopausal women.

Adult↗
PubMed1987

Reduced morbidity from skeletal metastases in breast cancer patients during long-term bisphosphonate (APD) treatment.

131 patients with osteolytic metastases from breast cancer were randomised to receive long-term oral treatment with aminohydroxy-propylidene-bisphosphonate (APD), 300 mg daily (n = 70), or to act as controls (n = 61) in a multicentre trial. Specific antitumour therapy was at the discretion of the clinician and variable. An interim analysis was made after a median follow-up of 13 months in the APD group and 14 months in the controls. There was a significant reduction in pathological fractures and severe bone pain in the APD group, and hypercalcaemia was prevented. Consequently the necessity for radiotherapy for skeletal complications was more than halved; the number of systemic therapy changes was also reduced. Gastrointestinal side-effects of APD led to a drop-out of 8% of patients. Oral supportive APD therapy is simple and convenient, and significantly reduced skeletal morbidity in advanced breast cancer.

Adult↗
PubMed1987

Progesterone receptor activity and relapse-free survival in patients with primary breast cancer: the role of adjuvant chemotherapy.

The prognostic significance of progesterone receptor activity (PgR) with regard to the estimated relapse-free survival (RFS) was studied in 350 one-center patients with primary breast cancer. All receptor assays were performed in one laboratory; PgR levels greater than 10 fmol/mg protein were considered positive. Univariate as well as multivariate statistical analyses were used to examine the prognostic significance of several variables. Eighty-nine of the 350 patients received adjuvant CMF chemotherapy (cyclophosphamide, methotrexate, and 5-fluorouracil). The median observation period was 69 months (range 12-125 months). In the group of 261 patients who did not receive adjuvant CMF, the PgR-status lacked prognostic significance; only the lymph node status significantly affected the RFS (p less than 0.00001). In contrast, in the CMF-treated group of patients, the PgR-status was the most powerful predictor of recurrence (p less than 0.001). Premenopausal CMF-treated patients with PgR+ tumors had a significantly longer RFS than those with PgR- tumors (p less than 0.02). The present data urge the need for a reappraisal of the prognostic significance of PgR and of the mechanism of action of adjuvant chemotherapy in primary breast cancer.

Analysis of Variance↗
PubMed1987

Progesterone receptor activity and the response to the first endocrine therapy in advanced breast cancer.

The predictive value of the progesterone receptor activity (PgR) was studied in a group of 84 patients with estradiol receptor (ER) positive advanced breast cancer who received their first endocrine treatment (tamoxifen or ovariectomy), with special emphasis on the timing of the receptor analysis. All patients were treated at 1 center and receptor analyses performed in 1 laboratory. In the group of 27 patients with PgR analysis performed immediately prior to the start of treatment, 14 out of 18 PgR+ve and only 2 out of 9 PgR-ve patients responded (P less than 0.02). In contrast, when PgR was analysed greater than 6 months prior to the start of treatment, the response rates for PgR+ve and PgR-ve patients did not differ significantly: 55% vs. 33% respectively. With regard to quantitative rather than qualitative PgR data, PgR levels exceeding 100 fmol/mg protein irrespective of ER levels, are an excellent indicator of hormonal responsiveness with a response rate of more than 80%, even if PgR analyses are performed long before the start of treatment.

Breast Neoplasms↗
PubMed1986

Cellular and plasma pharmacokinetics of weekly 20-mg 4'-epi-adriamycin bolus injection in patients with advanced breast carcinoma.

Weekly low-dose injections of 20 mg 4'-epi-adriamycin (E-ADM) were given to 12 patients with advanced postmenopausal breast cancer for at least 8 weeks. In advance, all patients were given hormonal therapy and polychemotherapy not containing anthracyclines. E-ADM concentrations in plasma and urine and in blood and bone marrow cells were determined during 8 consecutive weeks. Plasma concentrations in the range of a few nanograms per milliliter were seen up to 72-96 h. Cellular concentrations appeared to be more than 100-fold the plasma concentrations, and were 190 +/- 66 ng/10(9) cells on day 8, before the next injection was given. Nevertheless, no serious bone marrow toxicity was observed. In two patients with an increased plasma bilirubin concentration, cellular E-ADM concentrations were 20%-40% higher than those observed in the other patients. Plasma concentrations of E-ADM and 4'-epi-adriamycinol showed terminal half-lives 2-3 times longer and could be followed throughout the week. In three patients biopsies of skin metastases were examined. In two patients E-ADM could be demonstrated in the tumor tissue up to 7 days after the last injection. Although the number of patients investigated is too small to relate the drug kinetics to clinical response, it is of interest that the two patients with the highest cellular E-ADM concentrations responded better than the others.

Adult↗