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L V Beex

Publications and source records attributed to L V Beex.

At least 19 recordsLinked to original sources
PubMed1992

Human breast cancer: survival from first metastasis. Breast Cancer Study Group.

Survival from the detection of first metastasis (SAM) was analyzed in a single center series of 258 patients with advanced breast cancer. During the 15 year period covered by this study 230 patients died, 215 of their disease. The overall median SAM was 28 months. Univariate analysis of SAM stratified by first dominant site of metastasis, estrogen receptor status (ER), progesterone receptor status (PgR), tumor size, axillary lymph node status, patient age, menopausal status, and disease-free interval (DFI) showed the first dominant site of metastasis, ER, PgR, and axillary lymph node status to be significantly associated with SAM. Patients with visceral metastasis as first dominant site of metastasis had significantly shorter survival than those with either bone or soft tissue metastasis, median SAM 16 vs. 34 vs. 41 months respectively (P less than 0.001). SAM also differed according to the steroid hormone receptor status of the primary tumor: median SAM 34 and 33 months for patients with ER-positive or patients with PgR-positive tumors against 14 months for patients with ER-negative or with PgR-negative tumors (P less than 0.001). Patients with axillary lymph node involvement at primary disease had a shorter SAM than those without, median SAM 24 vs. 35 months (P = 0.006). No association between SAM and either tumor size, patient age, menopausal status, or DFI could be observed. Multivariate analysis including first dominant site of metastasis, ER, PgR, and axillary lymph node status showed the first dominant site of metastasis, ER, and axillary lymph node status to be independently associated with SAM.

Adult↗
PubMed1992

Dose intensity of chemotherapy with cyclophosphamide, methotrexate and 5-fluorouracil in the elderly with advanced breast cancer.

Toxicity and results of two different dose levels of chemotherapy with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) in older (greater than 70 years) patients with advanced breast cancer were evaluated in a prospective (non-randomised) study. During the first three courses of chemotherapy dose reduction for haematological toxicity was necessary in all of 10 and 8 of 13 patients treated with an intended dose of 100% and 75% of standard dose CMF, respectively. The median percentages of CMF, administered during the first three courses were about 75% in both groups of patients corresponding with a median dose intensity of 72% (range 49-87%) and 64% (range 36-78%) for patients of the 100% and 75% dose group, respectively. In 34 younger postmenopausal women (mean age 57 years) treated in our institution for advanced breast cancer the median percentages of CMF in the second and third course were 86% and 84%, respectively with a median dose intensity during the three courses of 82%. Dose reductions of CMF and bone marrow toxicity, though interdependent, were statistically significantly correlated with the endogenous creatinine clearance, but not with age. 1 patient died during severe leukopenia and thrombocytopenia. Non-haematological side effects were most pronounced in the 100% group. Results of therapy in both groups of patients were about equal and compared well with those of CMF therapy in general. It is advised that the dose of CMF in patients above 70 years should not exceed 75% of standard dose. Further dose reduction of methotrexate in case of severe renal failure is required.

Age Factors↗
PubMed1992

Epidermal growth factor receptors in human breast cancer: a plea for standardisation of assay methodology.

In a prospective study 200 primary human breast cancer specimens were analysed for epidermal growth factor receptor (EGFR) content by means of a multiple point ligand binding assay, proposed by the EORTC Receptor Study Group to be the standard EGFR assay. In 54% of the tumours the presence of saturable high affinity binding sites for epidermal growth factor could be demonstrated. The median EGFR level was 34 fmol/mg of membrane protein, the median Kd 0.50 nmd. Univariate analysis of the EGFR data stratified according to patient age, menopausal status, tumour size, axillary lymph node status, histological tumour type, tumour differentiation grade or the tumours' steroid hormone receptor status showed EGFR to be positively associated with younger age (P = 0.03), tumour dedifferentiation (P = 0.04) and steroid hormone receptor negativity (P less than 0.001). No association between EGFR and menopausal status, tumour size, axillary lymphnode status or histological tumour type could be demonstrated.

Adult↗
PubMed1992

Epidermal growth factor receptor levels are lower in carcinomatous than in normal colorectal tissue.

A series of 24 paired samples of colorectal carcinoma and the respective normal colorectal mucosa were analysed for Epidermal Growth Factor Receptor (EGFR) content by means of a standardised ligand binding assay. We, for the first time, found that EGFR levels are statistically significantly higher in normal colorectal mucosa biopsy samples than they are in colorectal carcinoma biopsy samples, the median EGFR levels being 77.5 fmol mg-1 of membrane protein (range 35-239), against 46 fmol mg-1 of membrane protein (range 22-81), respectively, P less than 0.001. In addition, we found that there are significant regional differences in EGFR expression in the normal human colon mucosa. The EGFR levels were significantly higher in samples from the proximal part of the colon than they were in samples from the distal part, the median EGFR levels being 124 fmol mg-1 of membrane protein (range 70-239) vs 55 fmol mg-1 membrane protein (range 35-156), P less than 0.05. The EGFR levels of the colorectal carcinoma samples did not show any regional variation.

Aged↗
PubMed1992

Results of cyclophosphamide and cisplatin combination chemotherapy in patients with ovarian carcinoma.

An unselected group of 30 patients with advanced epithelial ovarian cancer, FIGO stage IIb-IV, was treated with cyclophosphamide (750 mg/m2) and cisplatin (75 mg/m2) both administered intravenously on a single day at a 3-weeks interval (CP). At a median follow-up time of 25 months this treatment had resulted in a remission rate of 73% and an estimated median overall survival time of 29 months, which resembles the results of prospective randomized trials. Major side-effects encountered in our patients were renal toxicity and neurotoxicity requiring termination of chemotherapy with CP in 9 patients. Patients with residual tumor smaller than 1 cm had a significant survival benefit as compared to patients with residual tumor greater than 1 cm. Also, patients with stage III ovarian cancer had a significant longer duration of survival than patients with stage IV disease. After a median period of chemotherapy of 7 monthly the median time without symptoms of progression and without treatment was 9 months for patients with an objective remission. We found the CP regimen to be the best therapy to hand: improvement of the prognosis might be attained by other new treatment modalities.

Adult↗
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↗