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Biomedical subjects

M Dowsett

Publications and source records attributed to M Dowsett.

270 records · Page 15Linked to original sources
PubMed1982

Adjuvant aminoglutethimide therapy for postmenopausal patients with primary breast cancer: progress report.

A group of 122 postmenopausal patients with histologically proven node-positive primary breast cancer have been randomized to receive aminoglutethimide-hydrocortisone or placebo aminoglutethimide-placebo hydrocortisone for 2 years. Median follow-up is 17 months. In general, treatment was well tolerated, but 15 patients required a reduction in the dose of aminoglutethimide, and of these four patients were unable to continue therapy due to side effects. Primary staging, incidence of extensive node involvement, and estrogen receptor were similar in the treatment and control arms. Dehydroepiandrosterone sulfate (DHA-S) and estrone were measured in a subgroup of patients, and significant suppression of DHA-S levels throughout the duration of the treatment period as seen in patients receiving the active drug. No significant suppression of either DHA-S or estrone levels was seen in the controls. Patients were monitored for metastases by serial liver function tests, carcinoembryonic antigen, and chest X-rays, and of 26 relapsing patients only three patients were not detected by this screen. We conclude that adjuvant aminoglutethimide is moderately well tolerated. It is capable of suppressing DHA-S throughout 2 years of treatment. A further 280 patients will be entered into the study to assess the survival benefit for those taking aminoglutethimide-hydrocortisone.

Adult↗
PubMed1976

Breast-cancer osteolysis, bone metastases, and anti-osteolytic effect of aspirin.

23 (60%) of 38 human breast carcinomas had significant in-vitro osteolytic activity. All patients presenting with bone metastases or hypercalcaemia had active tumours. Over a subsequent three-year follow-up period, bone metastases did not develop in any of the 15 patients with inactive tumours, and metastases at other sites developed in only 2. Of the 23 patients with active tumours, 7 either had, or have since developed bone metastases; in 4 of these hypercalcaemia also developed. 14 tumours, chosen at random, were tested for in-vitro osteolytic activity in the presence and absence of aspirin, which inhibits prostaglandin synthetase. The activity of 8 of the 9 osteolytically active tumours was significantly, though not completely inhibited by aspirin. Although the number of patients is limited, these results indicate that the in-vitro osteolysis assay may detect substances, perhaps including prostaglandins, produced by breast tumours which affect prognosis and contribute to the subsequent formation of bone metastases.

Animals↗
PubMed1976

Human breast tumour-induced osteolysis and prostaglandins.

Osteolysis effected in vitro by breast carcinomas can be inhibited by aspirin. Some prostaglandins stimulate in vitro bone resorption. Our results indicate that whilst osteolytically active PGE and PGF are released by the carcinomas in most cases, some other osteolytic principle is released as well.

Aspirin↗
PubMed1975

Immunoreactive calcitonin production by human lung carcinoma cells in culture.

Monolayer cultures have been established from a poorly differentiated carcinoma of the lung. Homogeneous cell growth and morphology have been maintained for over 18 months through more than 80 subculture passages, and the cells have been found to produce both immunoreactive calcitonin and an immunoreactive carcinoembryonic antigen-like material.

Aged↗
PubMedDate not supplied

4-Hydroxyandrostenedione treatment for postmenopausal patients with advanced breast cancer.

We have treated 128 postmenopausal women with advanced breast cancer with 4-hydroxyandrostenedione. Of these, 118 were assessable for toxicity and 100 for response to treatment. Response to therapy was seen in 34% of patients and stabilization of disease in 12 patients. Three dose regimens were used (500 mg intramuscularly weekly; 250 mg intramuscularly every 2 weeks; and 500 mg orally daily). There was no difference in response in these three groups. Side effects were minimal and local reaction to injected drug was seen in 13% of patients. The sole severe side effect observed was neutropenia which was transient and reversible on discontinuing therapy. 4-Hydroxyandrostenedione is an effective nontoxic agent in the treatment of breast cancer.

Administration, Oral↗
PubMedDate not supplied

Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer.

The standard adjuvant endocrine treatment for postmenopausal women with hormone-receptor-positive localised breast cancer is 5 years of tamoxifen, but recurrences and side-effects restrict its usefulness. The aromatase inhibitor anastrozole was compared with tamoxifen for 5 years in 9366 postmenopausal women with localised breast cancer. After a median follow-up of 68 months, anastrozole significantly prolonged disease-free survival (575 events with anastrozole vs 651 with tamoxifen, hazard ratio 0.87, 95% CI 0.78-0.97, p=0.01) and time-to-recurrence (402 vs 498, 0.79, 0.70-0.90, p=0.0005), and significantly reduced distant metastases (324 vs 375, 0.86, 0.74-0.99, p=0.04) and contralateral breast cancers (35 vs 59, 42% reduction, 12-62, p=0.01). Almost all patients have completed their scheduled treatment, and fewer withdrawals occurred with anastrozole than with tamoxifen. Anastrozole was also associated with fewer side-effects than tamoxifen, especially gynaecological problems and vascular events, but arthralgia and fractures were increased. Anastrozole should be the preferred initial treatment for postmenopausal women with localised hormone-receptor-positive breast cancer.

Anastrozole↗
PubMedDate not supplied

Acquired tamoxifen resistance in human breast cancer and reduced intra-tumoral drug concentration.

Reduced intra-tumoral drug concentrations have been investigated as a mechanism of tamoxifen resistance in 51 patients with locally recurrent breast cancer. Serum tamoxifen was similar in patients with acquired and de-novo resistance, but intra-tumoral concentrations were significantly lower in patients with acquired resistance. Tumour oestrogen-receptor concentrations at relapse did not support the hypothesis that selective outgrowth of oestrogen-receptor-negative cells is a major mechanism for acquired tamoxifen resistance. Reduced intra-tumoral tamoxifen levels during prolonged therapy may be an important mechanism for acquired resistance in breast cancer.

Aged↗
PubMedDate not supplied

Recent advances in the clinical application of aromatase inhibitors.

Aromatase inhibitors have evolved over a period of 20 years to well tolerated agents that can effectively obliterate aromatase activity in postmenopausal women. Breast cancer is the predominant clinical application and here the newer agents have established themselves as the preferred second-line agent after tamoxifen in the treatment of advanced disease. Recent data indicate that they be more efficacious than tamoxifen and, therefore, may replace it as the first-line agent of choice in the near future. On-going clinical trials in the adjuvant setting and prospective prevention studies will elucidate whether these drugs have a yet greater role in breast cancer.

Antineoplastic Agents↗
PubMedDate not supplied

The mechanisms of human tumour-induced osteolysis and hypercalcaemia.

This is a brief resume of the current knowledge regarding the mechanisms whereby tumours may cause the breakdown or increase the turnover of bone matrix resulting in hypercalcaemia. The precise mechanisms and agents still remain to be ascertained. This would appear to be an investigative area worthy of significant research effort in view of the potential benefit to patient care which may then ensue.

Breast Neoplasms↗