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Biomedical subjects

R D Rubens

Publications and source records attributed to R D Rubens.

At least 55 records · Page 3Linked to original sources
PubMed1994

Expression of tumour necrosis factor (TNF alpha) and its receptors in benign and malignant breast tissue.

As well as having anti-tumour activity in animal models. TNF alpha has been implicated in the promotion of tumour invasion and metastasis. Expression and localization of TNF alpha mRNA and protein has been investigated in a series of benign and malignant breast tissues. TNF alpha mRNA was expressed in a minority of cells (< 0.5%) in 4/11 cases of benign breast tissue and in a higher proportion of invasive carcinomas (43/49 cases). Expression of TNF alpha mRNA was focal and confined to the tumour stroma. The presence of TNF alpha was confirmed by immunohistochemistry and again was predominantly stromal. Expression of mRNA and protein localized to infiltrating macrophages defined by the antibody EBM/11 in adjacent sections and using 2-colour immunofluorescence. Although the average number of macrophages per high-power field did not vary among invasive carcinomas of different histological type or grade, the number of cells expressing TNF alpha increased with increasing tumour grade. Immunodetectable p75 TNF receptor and to a lesser extent p55 receptor was present on cells of the mononuclear infiltrate and on the endothelium of invasive carcinomas, but not on the tumour cells themselves.

Breast↗
PubMed1994

Serum progesterone at the time of surgery and survival in women with premenopausal operable breast cancer.

Serum progesterone and oestradiol levels have been measured in 210 premenopausal women with operable breast cancer on samples taken within 3 days of tumour excision. There was no relation between oestradiol level and time since last menstrual period, nor any effect of oestradiol value on prognosis. However, serum progesterone levels were related to the phase of the cycle as determined by time since last menstrual period. When divided on a basis of levels > 1.5 ng/ml (luteal phase) and < or = 1.5 ng/ml, it was found that there was no difference in survival between the two groups among 117 axillary node negative cases. However, in the 93 patients with positive axillary nodes, higher progesterone levels were associated with significantly better survival. Thus, serum progesterone levels at the time of surgery may affect the prognosis of premenopausal node positive patients with operable breast cancer.

Breast Neoplasms↗
PubMed1994

Iododoxorubicin in advanced breast cancer: a phase II evaluation of clinical activity, pharmacology and quality of life.

Iododoxorubicin 80 mg m-2 i.v. was given 3 weekly for a maximum of six cycles as first-line chemotherapy to 14 evaluable women with metastatic breast cancer. The response rate was 14% (95% confidence intervals 4-40%); median time to progression was 3.5 months (range 0.7 to > 9.3) and median survival was 10.2 months (range 2.3 to > 20.4). Neutropenia was the main toxicity but was not associated with severe sepsis. Two patients had a significant (> 10%) but asymptomatic fall in cardiac ejection fraction; other toxicities were mild. Plasma pharmacokinetics was studied during the first cycle of treatment. Iododoxorubicin was extensively metabolised to iododoxorubicinol. Neutropenia and thrombocytopenia were both significantly correlated with the area under the concentration-time curve (AUC) for iododoxorubicin and the total AUC for iododoxorubicin and iododoxorubicinol. Quality of life (QOL), evaluated by self-report questionnaire and interview, showed little evidence of benefit in terms of physical symptom relief, level of activity, psychological symptoms or global evaluation of QOL during treatment. Iododoxorubicin is subjectively less toxic than standard anthracyclines, but at the dose and schedule used has limited activity in metastatic breast cancer, possibly because iododoxorubicinol is not clinically active.

Adult↗
PubMed1994

Phosphorus-31 metabolism of post-menopausal breast cancer studied in vivo by magnetic resonance spectroscopy.

We have studied the metabolism of 31P-containing metabolites of post-menopausal breast cancers in vivo using magnetic resonance spectroscopy (MRS) and a 5.5 cm surface coil. Spectra were acquired from 23 diameter. The spectra of the 19 previously untreated tumours had significantly higher phosphomonoester (PME) 31P relative peak areas than the normal breasts of eight post-menopausal women (11.7% and 7.7% respectively, P = 0.002). Although an increased PME relative peak area was characteristic of malignancy, PME relative peak area is similarly raised in lactating breast and, therefore, not a specific feature of cancer. An apparently lower nucleotide triphosphate (NTP) relative peak area in tumours than healthy postmenopausal breast was secondary to the differences in PME relative peak area; contamination by signal from chest wall muscle probably accounts for the ostensibly higher phosphocreatine (PCr) relative peak area of the tumours. Spectroscopy was repeated following chemotherapy in six women. An increase in PCr relative peak area was seen in all five patients who responded, but again this may represent increased contamination secondary to changes in tumour size. A fall in PME relative peak area was noted in four responders, but also one non-responder, so this finding may not be sufficiently specific to be of use clinically. Further studies are need to elucidate fully the role of MRS in breast cancer.

Adult↗
PubMed1994

The effects of chemotherapy on morphology, cellular proliferation, apoptosis and oncoprotein expression in primary breast carcinoma.

The use of chemotherapy as a form of primary treatment for breast cancer is increasing and, as a result, more resection specimens contain tumours which have been exposed to cytotoxic drugs. We have studied the effects of chemotherapy on the tumour morphology and various biological features of breast carcinoma in a group of 35 patients. These were a group who responded to treatment in a clinical study of the use of primary chemotherapy designed to reduce tumour bulk prior to surgery. Characteristic morphological changes, temporally related to the administration of cytotoxic agents, are seen. The malignant cells become enlarged with vacuolated cytoplasm and vesicular nuclei containing prominent nuclei; occasionally the nuclei were angular and hyperchromatic. These features are interpreted as degenerative in nature. In 15 cases sufficient material was present in the pretreatment biopsies to compare the grade of the tumours before and after chemotherapy: changes were found in six tumours. Cytotoxic drugs do not induce a consistent pattern of change in the proliferation and apoptotic indices of individual tumours, but there is a tendency to reduce proliferative activity over all the tumours as a group. It was also found that chemotherapy is capable of modifying the expression of the oncoproteins c-erbB-2 and p53 in a minority of cases of breast cancer, usually resulting in an acquisition of immunoreactive oncoprotein. It is important to be aware of these effects when studying breast carcinomas removed after chemotherapy.

Adult↗
PubMed1994

A phase II, multicentre, UK study of vinorelbine in advanced breast cancer.

Thirty-four evaluable patients were treated with vinorelbine, a novel, semisynthetic vinca alkaloid, as first-line chemotherapy for advanced breast cancer. They received vinorelbine 25 mg m-2 i.v. given weekly for a maximum of 16 cycles. Two patients achieved a complete remission and 15 a partial remission, giving a response rate of 17/34 (50%; 95% CI of 34-66%); median response duration was 5.8 months. The median progression-free interval was 4.4 months and median survival 9.9 months. Treatment was generally well tolerated. Fatigue was the most common side-effect. The main reason for dose adjustments was myelosuppression; 68% of patients had WHO grade 3 or 4 neutropenia and there was one death attributed to neutropenic sepsis. Nausea/vomiting and neuropathy were mild and alopecia was uncommon. This study confirms vinorelbine as a highly active, well-tolerated agent in advanced breast cancer worthy of evaluation in combination chemotherapy regimens.

Adult↗
PubMed1994

Expression of sialyl-Tn predicts the effect of adjuvant chemotherapy in node-positive breast cancer.

Sialyl-Tn (STn) is a carcinoma-associated carbohydrate determinant expressed on cancer-associated mucins and has the structure NANA alpha(2-6)alpha GalNAc. Expression of STn in colon and ovarian cancer is associated with a poor prognosis independent of tumour grade, stage or histological type. We have examined 237 cases of primary breast cancer for expression of this antigen using the antibody HB-STn (Dako). The frequency of STn expression was 31% in the whole group, 36% in the node-negative and 28% in the node-positive group. Survival was lower, but not significantly so, in the STn-positive group (P = 0.07), but this effect was highly significant for patients with node-positive disease (P < 0.002), the curves for node-negative disease being coincident (P = 0.31). In node-positive disease the effect was limited to those receiving adjuvant chemotherapy (P = 0.001). In a multivariate (Cox) analysis on the whole group STn staining, combined with adjuvant chemotherapy, showed a highly significant correlation with survival. In STn-negative cases, adjuvant chemotherapy improved survival (relative risk 2.3, 95% confidence intervals 1.4-3.9), whereas adjuvant chemotherapy did not influence survival in patients which expressed STn (relative risk 1.1, 95% confidence intervals 0.6-2.2). Thus, by either direct or indirect mechanisms, STn positivity appears to be a marker of resistance to adjuvant chemotherapy.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1994

Therapy for metastatic breast cancer.

Our understanding of mechanisms of resistance to endocrine treatment has increased; they include mutations in steroid receptors and altered metabolism of tamoxifen. Tamoxifen and progestogens appear to have similar efficacies for first-line endocrine treatment, but high doses of progestogens have been shown to give less cost-effective results compared with conventional doses. Numerous new endocrine and cytotoxic agents have been reported, but no major new treatments have been identified. High-dose chemotherapy for metastatic disease remains experimental. The concept of estrogen recruitment to enhance chemosensitivity has not been corroborated. Prior adjuvant systemic treatment renders treatment of relapsed breast cancer less effective.

Breast Neoplasms↗
PubMed1993

Patterns of metastatic breast cancer in relation to histological type.

We have examined the clinical records fo 1238 patients with operable breast cancer to identify the sites of metastatic disease. Infiltrating ductal carcinoma (IDC) recurred more commonly in lung (P < 0.05), pleura (P < 0.05) and brain (P < 0.05), while infiltrating lobular carcinoma (ILC) more commonly metastasised to the bone marrow (P < 0.01) and peritoneum (P < 0.01). Bone involvement as the initial presentation of distant metastatic disease occurred in over 50% of women with ILC, significantly more commonly than in those with IDC (34%, P < 0.01). Survival was similar for the two groups, both from time of diagnosis and from time of development of distant metastases.

Adult↗
PubMed1993

The influence of adjuvant chemotherapy on outcome after relapse for patients with breast cancer.

This study examines the outcome following relapse for 176 patients who had been entered into a randomised trial comparing adjuvant cyclophosphamide, methotrexate and 5-fluorouracil (CMF) with no adjuvant therapy (controls). Relapse has occurred in 65/144 (45%) of the CMF group and 111/158 (70%) of controls (P < 0.0001). 123/176 patients received endocrine treatment after relapse with higher response rates (38 vs. 18%, P < 0.05) and longer time to progression (23 vs. 19 weeks, P = 0.03) for controls. 94/176 received chemotherapy after relapse again with higher response rates (47 vs. 23%, P = 0.05) and longer time to progression (17 vs. 9 weeks, P = 0.03) for controls. Despite this, survival after relapse was the same for the two groups (median 16 months). However, on subgroup analysis, postmenopausal patients who had received adjuvant CMF had shorter survival (P = 0.03). These results suggest that prior adjuvant therapy should be a stratification factor in clinical trials in advanced disease.

Adult↗
PubMed1993

Radiographic patterns of intrathoracic disease in breast carcinoma: prognostic implications.

The chest radiographic appearances of patients with intrathoracic metastases from breast cancer are variable and their relationship to patient outcome is unknown. This study aimed to classify and determine the frequency of various radiographic patterns and, in addition, to establish whether these patterns can be used to predict patient prognosis. A retrospective study was made of the patients of a major breast unit who over a 3 year period were found to have developed intrathoracic metastases. In each case, the earliest plain chest X-ray showing signs of metastasis was reviewed and the frequency of the different radiographic patterns determined. Comparison was made between these patterns and patient mortality. The chest radiographs of 92 patients who developed intrathoracic metastases during a 3 year period were analysed. Pulmonary nodules were found in 66%, pleural effusions in 41% (bilateral in 18%), lymphadenopathy in 25%, lymphangitis in 18% and pleurally-based nodules in 11%. Median survival of the whole group was 13.5 months. Patients with bilateral, but not unilateral, effusions had a significantly poorer prognosis (median survival 3 months). Although the median survival of patients with lymphangitis seemed poor (5.5 months), this difference was not statistically significant. Multivariate analysis showed bilateral effusions to be the only independent predictor of worse outcome. We have found that of the plain radiographic patterns seen in intrathoracic metastasis from breast cancer, only bilateral pleural effusions can be used to predict a worse prognosis than that associated with intrathoracic metastasis as a whole.

Adult↗
PubMed1993

Psychiatric disorder in patients with advanced breast cancer: prevalence and associated factors.

The prevalence of psychiatric disorder and associated factors has been examined in 139 women with advanced breast cancer. Patients completed a self-report assessment of mood, the Hospital Anxiety and Depression Scale (HAD). They were also interviewed to obtain sociodemographic details, UICC performance status and past psychiatric history. Overall, 35 (25%) scored 11 or above (out of a maximum of 21) on either the anxiety or the depression subscales, or both, of the HAD and were therefore probable cases of anxiety and/or depression. These patients are likely to benefit from psychosocial intervention. Clinical anxiety was unrelated to any sociodemographic or disease related factors. Clinical depression was significantly more prevalent amongst patients in the lower socioeconomic classes (P = 0.01) and those with poor performance status (P = 0.007). Depression can be difficult to detect in patients with advanced breast cancer and these factors may be useful indicators to clinicians of patients at high risk of this disorder.

Adult↗
PubMed1993

Cost effectiveness in the treatment of advanced solid tumours.

When the treatment of advanced cancer is palliative in intent, evaluation of quality of life is of paramount importance in judging the effectiveness of treatment. The balance between adverse effects (costs) and benefits has been particularly difficult to determine with cytotoxic drugs. An approach to this problem using medical audit is described. It has been found to be a reliable method which has demonstrate a highly significant correlation between achievement of objective regression and acquisition of benefit. The method is now undergoing corroboration by a prospective study.

Antineoplastic Agents↗
PubMed1993

Advanced breast cancer: use of resources and cost implications.

Little information is currently available on the use of hospital resources and the resulting costs of treating any advanced cancer. Such data may be useful for planning purposes and for calculating the cost effectiveness of measures designed to reduce the incidence of advanced disease (such as the National Breast Screening Programme). A retrospective analysis of the medical records of 50 patients with advanced breast cancer who attended the Guy's Hospital Oncology Unit and who died between October 1988 and December 1990 has therefore been undertaken. For each patient, the duration of in-patient stays and principal indications for admissions were recorded, together with the number of out-patient attendances. Details of endocrine treatment, chemotherapy and radiotherapy were abstracted as were all radiological and laboratory investigations. Costs for each of these activities were calculated. The median duration of advanced disease was 17 months (mean 27 months; range 7 days-12 years). The mean cost of treatment per patients was calculated to be 7,620 pounds (range 317 pounds-27,860 pounds). Mean duration of in-patient stay was 32 days (0-133) and this accounted for 56% of total costs. The large majority (> 80%) of the time spent as an in-patient was for the care of serious illness rather than for specific antitumour treatment. Cytotoxic drugs accounted for 9% of the total cost, compared with 8% for radiotherapy and 13% for laboratory and radiological investigations.

Adult↗