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Biomedical subjects

R D Rubens

Publications and source records attributed to R D Rubens.

At least 73 records · Page 4Linked to original sources
PubMed1993

Activity of type IV collagenases in benign and malignant breast disease.

Using zymography and computer assisted image analysis, we have measured the levels of type IV collagenases in biopsies from normal breast, and benign and malignant breast disease. The 92 kDa form was present in three of 11 cases of normal/benign disease, three of nine grade I tumours, four of 12 grade II tumours, but 11 of 11 grade III tumours. Mean levels were higher in grade III tumours (P < 0.0001). When the levels of 72 kDa collagenase and its active 62 kDa form were considered together, there was no difference between the benign and malignant cases (P = 0.55), but the amount of active enzyme, considered as a proportion of the 62 + 72 kDa forms, was significantly higher in malignant disease (P = 0.003). There was also a trend towards a higher proportion of active enzyme with increasing tumour grade (P < 0.0001). In situ hybridisation and immunohistochemistry studies showed that that mRNA and protein for the 92 kDa enzyme was primarily found in the tumour stroma. mRNA for the 72 kDa enzyme was also found in stromal areas. This study demonstrates a clear relationship between production of Type IV collagenases and malignant breast disease. Inhibitors of these enzymes may be of value in preventing metastatic disease.

Breast↗
PubMed1993

Spinal cord compression in breast cancer: a review of 70 cases.

Spinal cord compression (SCC) is a relatively uncommon but frequently disabling complication of metastatic breast cancer. We have conducted this retrospective study of 70 patients with SCC secondary to breast cancer with the aims of determining risk factors for its development and predictors of outcome. Median age at diagnosis of breast cancer was 51 years with median time to SCC 42 months. All patients had radiological evidence of bone metastases at the time of SCC, and only five were not known to have bone metastases prior to SCC. The most frequent symptom of SCC was motor weakness (96%) followed by pain (94%), sensory disturbance (79%) and sphincter disturbance (61%). Ninety-one percent of patients had at least one symptom for more than a week. Radiotherapy (RT) was given as primary treatment in 43 cases, whilst 21 had decompressive surgery and seven of these went onto have postoperative radiotherapy. Six patients were deemed too unwell for either modality. Following treatment, 96% of those who were ambulant before therapy maintained the ability to walk. In those unable to walk, 45% regained ambulation, with RT and surgery being equally effective. Median survival following SCC was 4 months, with no significant difference between those treated by RT or surgery. The most important predictor of survival was ability to walk after treatment, followed by time from diagnosis of breast cancer to SCC. We conclude that the majority of patients have warning symptoms of SCC and that nearly all will have evidence of spinal bone metastases before compression occurs. The results suggest that earlier diagnosis and intervention could improve outcome. There was no evidence of benefit from surgery over radiotherapy as primary treatment, survival in both treatment groups being poor.

Adult↗
PubMed1993

Chemotherapy of advanced breast cancer: outcome and prognostic factors.

The outcome for 758 consecutive patients who had received one or more chemotherapy regimens for recurrent or metastatic breast cancer is presented. The response rate following first line treatment was 34%. Median duration of response was 7.8 months, median time to progression was 3.7 months and median survival was 7.9 months. The only factor predicting for response, of factors recorded at presentation and at initiation of chemotherapy, was the use of anthracycline based regimens, though this may reflect the patient selection policy. Initial disease free interval, presence of liver metastases and use of anthracyclines were significantly related to time to progression. Several factors related to survival following first chemotherapy, but anthracycline usage showed only a very weak correlation. One third of patients (249/758) received two or more chemotherapy regimens. The response rate (16%) and median time to progression (2.3 months) were significantly worse than for first line treatment. The outcome after third line chemotherapy was very similar to that observed following second line treatment. Achievement of an objective response with first line chemotherapy predicted for second response, but with insufficient power to be of use in selecting patients for subsequent chemotherapy. Time to progression following first line chemotherapy did not influence that after second line treatment.

Adult↗
PubMed1993

Metastatic breast cancer.

The place of tamoxifen in the treatment of metastatic breast cancer is being challenged by the development of less estrogenic antiestrogens. New inhibitors of aromatase and estrone sulfatase have been reported. Anthrapyrazoles are new cytotoxic agents with high activity and low toxicity. Uncertainty about the optimal duration of chemotherapy continues. Methods to intensify chemotherapy, enabled by bone marrow support techniques, continue to be studied, but a routine role for this approach in palliative treatment of metastatic disease has not been established. Active specific immunotherapy appears to be practicable following identification of defined tumor-associated immunogens. Evidence for the ability of bisphosphonates to reduce morbidity from bone metastases continues to accumulate.

Antineoplastic Agents↗
PubMed1993

Improving treatment for advanced breast cancer.

Treatment for advanced breast cancer is not yet curative but aims to palliate the disease to make life as symptom free and as active for as long as possible with the minimum of adverse effects of treatment. The high prevalence and often long time course of the disease leads breast cancer to make major demands on health care resources. Radiotherapy is valuable for localized lesions, but more widespread disease relies on systemic treatment. Tamoxifen is the main agent for endocrine therapy, although aromatase inhibitors and progestogens are also important. Improvements in cytotoxic chemotherapy have come as much from methods to reduce toxicity as from new agents. Intensive chemotherapy with bone marrow support has not found a routine place in advanced breast cancer, but experience gained may have more application in the adjuvant treatment of high risk operable disease. Incorporation of quality of life measures is being increasingly recognized as essential for the proper evaluation of response to treatment. Although postoperative adjuvant systemic therapy now has an established place for early breast cancer, subsequent relapse responds less well to either endocrine or cytotoxic agents. Bone metastases are a major problem in advanced breast cancer, most of the damage being mediated by the stimulation of osteoclasts by tumour derived cytokines. Important advances in treatment have come from the use of bisphosphonates and beta emitting isotopes. Monitoring of bone metastases is enhanced by using biochemical parameters of response in addition to imaging techniques.

Aged↗
PubMed1992

Mastectomy or conservation for early breast cancer: psychological morbidity.

A consecutive series of 197 women under 70 years of age with operable breast cancer, randomised to treatment by a conservation technique in comparison to mastectomy, were assessed using structured interviews. The prevalence of cases of anxiety and depression was high before treatment commenced, there were fewer cases in the conservation group but no significant difference at 3 or 12 months in the number of new cases, social adjustment, or capacity to return to work. Attitudes to treatment showed significant differences between the groups, more women in the conservation group were able to wear their usual clothes and most women rated the cosmetic result highly. Patients were more likely to stop sexual intercourse completely after mastectomy. An effective conservation technique should be an attractive treatment choice available to selected women with early breast cancer.

Aged↗
PubMed1992

DNA flow cytometry and response to preoperative chemotherapy for primary breast cancer.

Between October 1988 and June 1990, 22 patients with locally advanced, inoperable breast cancer entered a pilot study of four cycles of anthracycline based cytotoxic chemotherapy followed by surgery and tamoxifen. Fine needle aspirate samples of tumour were obtained for DNA flow cytometry before treatment and during the first cycle of chemotherapy. 21 patients are eligible for assessment of response and toxicity. Chemotherapy was well tolerated with greater than WHO grade 2 vomiting or stomatitis in 4 patients. Granulocytopenia less than 10(9)/l was noted in 16/21 patients but there were no episodes of neutropenic sepsis. There were 7 complete responses (CR) and 11 partial responses (PR), giving an overall response rate to chemotherapy (CR+PR) of 18/21 (86%). Responses were observed more commonly in patients who had aneuploid tumours (P = 0.06) and in patients whose tumours had a high S-phase fraction (P = 0.1). Tumours which responded to chemotherapy (CR or PR) had a significantly higher median SPF compared with tumours which did not regress (P less than 0.05). There was no consistent pattern of change in SPF values during the first cycle of chemotherapy, either for patients who responded to treatment or for those whose tumours did not regress. This combination therapy is well tolerated with a high response rate. The results of this pilot study support the recent suggestion that tumours with rapidly proliferating, aneuploid populations of cells exhibit the best short-term response to chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Preliminary results of the use of urinary excretion of pyridinium crosslinks for monitoring metastatic bone disease.

The collagen crosslinks, pyridinoline and deoxypyridinoline, are recently described markers of the rate of bone resorption. The urinary excretion of these compounds, expressed as a ratio to urinary creatinine, has been measured using ion-pair reversed phase high-performance liquid chromatography in 20 patients receiving oral pamidronate for bone metastases from breast cancer. Before treatment the ratio of pyridinoline and deoxypyridinoline to creatinine in urine (UPCR and UdPCR respectively) were each above normal in 16/20 (80%) patients. Urinary calcium excretion (UCCR) was elevated in 15/20 (75%). There was a strong correlation between UPCR and UdPCR, but neither of the crosslink measurements correlated well with UCCR. Urinary excretion of all three indices of bone resorption fell significantly during pamidronate treatment. The median values after 4 weeks treatment were 63% of baseline for UPCR, 45% for UdPCR and 26% for UCCR. From this preliminary study urinary pyridinoline and deoxypyridinoline excretion appear to be promising markers of bone resorption in advanced malignancy. Their role in response assessment and the advantages over UCCR measurements merit further study.

Administration, Oral↗
PubMed1992

Clinical pharmacokinetics of epirubicin: the importance of liver biochemistry tests.

The influence of liver biochemistry tests on epirubicin pharmacokinetics has been investigated in 52 women with advanced breast cancer, 27 of whom had radiologically proven liver metastases. Patients received epirubicin 12.5-120 mg m-2 given as an i.v. bolus. Epirubicin levels were measured by HPLC following the first cycle of treatment. Epirubicin elimination, expressed as clearance (dose/AUC), in the 22 patients with normal AST and bilirubin was compared with that of 30 patients with a raised AST +/- raised bilirubin. Epirubicin clearance was significantly reduced in the patients with a raised AST, whether their serum bilirubin was normal (22 patients) or elevated (eight patients). In the 30 patients with a raised AST +/- raised bilirubin, epirubicin clearance correlated strongly with the level of AST (r = -0.72) but not with serum bilirubin, alkaline phosphatase, albumin or creatinine. Using a multiple regression analysis, AST was the only one of these biochemical variables predictive of epirubicin clearance (r2 = 0.47, P = 0.0006). We conclude that a raised serum AST is a more sensitive and reliable measure of abnormal epirubicin pharmacokinetics than increased bilirubin. These findings have implications for anthracycline treatment in patients with abnormal liver biochemistry.

Adult↗
PubMed1992

Metastatic breast cancer and its complications.

Tamoxifen is now established for use in premenopausal as well as postmenopausal patients. Recent reports have not shown its activity to be enhanced by the addition of either prednisolone, progestogens, or interferon. Reversible ocular toxicity from tamoxifen appears to be more common than had been previously realized. Different schedules giving the same dose intensity of doxorubicin give markedly different pharmacokinetic profiles. Although this does not lead to differences in responses or physical toxicity, it seems to have important implications for quality of life. Taxol is showing impressive activity in advanced breast cancer, and significant response rates have also been reported for carboplatin and podophyllotoxin derivatives. To achieve maximum effectiveness from the cyclophosphamide, methotrexate, and fluorouracil combination, attention to schedule and dose intensity has been shown to be important. No new effective cytotoxic combinations have been described. High-dose chemotherapy requiring bone marrow support remains experimental. Further progress has been made in monitoring the response of metastatic bone disease to treatment. The precise significance for patients of the results in many of the papers reviewed is often uncertain because they lack quality-of-life measures; the importance of this approach is emphasized.

Antineoplastic Combined Chemotherapy Protocols↗