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Biomedical subjects

R D Rubens

Publications and source records attributed to R D Rubens.

At least 19 recordsLinked to original sources
PubMed2004

The interaction of oestrogen receptor status and pathological features with adjuvant treatment in relation to survival in patients with operable breast cancer: a retrospective study of 2660 patients.

The oestrogen receptor (ER) status of 2660 patients with primary breast cancer has been related to the effect of different adjuvant systemic therapies on survival. However, as patients in the various treatment groups also had different prognostic features comparison between treatments was difficult. Over 90% of patients receiving tamoxifen (Tam) were postmenopausal compared with <20% of those receiving chemotherapy (CT). The latter had more positive nodes (85% vs 54%) and grade III tumours (54% vs 30%) than the Tam group. The combined CT and Tam group had similar characteristics to the CT alone group. The current reported increase in the proportion of women with ER+ tumours is explained by immunohistochemical analysis of ER and screening programmes. ER status was unrelated to survival in patients with small, low grade, node-negative tumours which was no different from that expected for age-matched women taken from the general population. The value of adjuvant treatment in these patients is therefore questionable. In those given any adjuvant treatment, survival of women with ER+ tumours was prolonged, with the greatest effect being seen in those receiving Tam. Patients with ER- tumours benefited from CT but the addition of Tam to CT improved survival only in those with ER+ tumours. ER status is now established as a major predictive factor for treatment selection in primary disease. Studies of prognostic and predictive markers may be invalidated by use of adjuvant therapy and selection criteria for different treatments. Survival will be influenced by both tumour biology and therapy. This important consideration must be remembered when analysing new markers, particularly in small studies.

Breast Neoplasms↗
PubMed2003

Epirubicin in patients with liver dysfunction: development and evaluation of a novel dose modification scheme.

This study aimed to develop an epirubicin dose modification scheme in women with breast cancer and liver dysfunction. We first identified target areas under the concentration-time curve (AUCs) of 2400 and 1600 ng/ml.h from pharmacokinetic studies in 15 women with normal liver tests. In a second group of 16 women with abnormal liver biochemistry, the relationship between raised asparate aminotransferase (AST) and epirubicin clearance was: dose=AUC (97.5-34.2xlog AST). Adaptive dosing was evaluated prospectively in a third group of 41 women with serum AST > or =2xnormal+/-raised bilirubin. The median AUCs were 2444 and 1608 ng/ml.h, close to the high and low target AUCs, respectively. Variability in AUC was lower with adaptive dosing than in a fourth group given an unadjusted dose of epirubicin (coefficient of variation=25.8, 30.0 and 46.5%, respectively; P=0.06). Epirubicin dosing based on AST is safe and may reduce pharmacokinetic variability.

Adult↗
PubMed2001

Metastatic eccrine porocarcinoma: response to docetaxel (Taxotere) chemotherapy.

BACKGROUND: Eccrine porocarcinoma is an uncommon neoplasm of the intra-epidermal sweat gland duct. PATIENTS AND METHODS: A case of eccrine porocarcinoma in a female renal transplant patient aged 45 years is described with a review of pertinent literature. RESULTS: The primary tumour was highly pleomorphic. In places large and small cells merged and focally the former component infiltrated the epidermis in a manner akin to Paget's disease of the breast. The majority of the tumour was high grade; using the modified Bloom and Richardson grading system, usually applied to mammary ductal carcinomas, the tumour graded as 3. Metastatic disease developed nine months following primary surgical treatment. The metastatic eccrine porocarcinoma was resistant to epirubicin but responded to docetaxel chemotherapy. CONCLUSIONS: There are no data to support the use of adjuvant therapy in the management of eccrine porocarcinoma. The use of the modified Bloom and Richardson grading system may define cases at high risk of relapse in which adjuvant therapy might be considered. Metastatic eccrine porocarcinoma has proven resistant to many chemotherapeutic agents. We report the first use of docetaxel in the management of this disease. The treatment was well tolerated and resulted in marked symptomatic and radiological responses. Treatment with docetaxel should be considered in future cases of this rare tumour.

Acrospiroma↗
PubMed2001

7. Management of advanced breast cancer.

Approximately half the patients with breast cancer relapse with locally recurrent or metastatic disease. This disease is incurable but can often be controlled, sometimes for many years. Careful clinical evaluation and restaging provides a baseline reference against which response can be judged. Investigations are selected but may include biochemical screens, blood counts, chest X-ray, isotopic bone scan and radiographs of abnormal regions. Selection of systemic treatment is based on three key factors: the extent, pattern and aggressiveness of the disease; hormone sensitivity; and menstrual status. Chemotherapy is used for rapidly progressing visceral disease such as lymphangitis carcinomatosa or hepatic metastases with deranged liver biochemistry where death ensues rapidly unless disease progression can be reversed. With less aggressive disease, treatment is planned around the oestrogen and progesterone status of the tumour. Those with low tumour receptor levels are unlikely to respond to endocrine treatment and chemotherapy should be considered. For patients with steroid receptor-positive tumours, endocrine treatment is used before chemotherapy is needed and consideration of menstrual status can assist in the selection of the precise approach.

Antineoplastic Agents↗
PubMed2000

Risk of complications from bone metastases in breast cancer. implications for management.

A retrospective analysis of 859 patients who developed bone metastases from breast cancer between 1975 and 1991 was performed in order to identify factors that predict for complications from skeletal disease. The patients were divided into four groups based on the sites of disease at diagnosis of skeletal metastases: bone disease only; bone and soft tissue disease; bone and pleuro-pulmonary disease; bone and liver disease. Patients with metastatic disease confined to the skeleton were most likely to develop a pathological fracture. The time to long bone fracture was similar for all groups, but the least number of such fractures occurred in patients with bone and liver metastases since their survival was shortest (median: 5.5 months; P<0.001). Patients with bone metastases only were most likely to require radiotherapy to painful osseous deposits (P=0.0001) and most rapidly developed spinal cord compression (P=0.01, data not shown). The results suggest that patients with disease confined to the skeleton at the diagnosis of bone metastases are most likely to develop skeletal-related complications from advanced breast cancer. Such patients may benefit most from treatment with bisphosphonates.

Bone Neoplasms↗
PubMed1999

Use of positron emission tomography in evaluation of brachial plexopathy in breast cancer patients.

18-Fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) has previously been used successfully to image primary and metastatic breast cancer. In this pilot study, 19 breast cancer patients with symptoms/signs referrable to the brachial plexus were evaluated with 18FDG-PET. In 11 cases computerized tomography (CT) scanning was also performed. Of the 19 patients referred for PET study, 14 had abnormal uptake of 18FDG in the region of the symptomatic plexus. Four patients had normal PET studies and one had increased FDG uptake in the chest wall that accounted for her axillary pain. CT scans were performed in 9 of the 14 patients who had positive brachial plexus PET studies; six of these were either normal or showed no clear evidence of recurrent disease, while three CTs demonstrated clear brachial plexus involvement. Of two of the four patients with normal PET studies, one has had complete resolution of symptoms untreated while the other was found to have cervical disc herniation on magnetic resonance imaging (MRI) scan. The remaining two patients almost certainly had radiation-induced plexopathy and had normal CT, MRI and PET study. These data suggest that 18FDG-PET scanning is a useful tool in evaluation of patients with suspected metastatic plexopathy, particularly if other imaging studies are normal. It may also be useful in distinguishing between radiation-induced and metastatic plexopathy.

Adult↗
PubMed1999

The influence on survival of delay in the presentation and treatment of symptomatic breast cancer.

The aim of this study was to examine the possible influence on survival of delays prior to presentation and/or treatment among women with breast cancer. Duration of symptoms prior to hospital referral was recorded for 2964 women who presented with any stage of breast cancer to Guy's Hospital between 1975 and 1990. Median follow-up is 12.5 years. The impact of delay (defined as having symptoms for 12 or more weeks) on survival was measured from the date of diagnosis and from the date when the patient first noticed symptoms to control for lead-time bias. Thirty-two per cent (942/2964) of patients had symptoms for 12 or more weeks before their first hospital visit and 32% (302/942) of patients with delays of 12 or more weeks had locally advanced or metastatic disease, compared with only 10% (210/2022) of those with delays of less than 12 weeks (P < 0.0001). Survival measured both from the date of diagnosis (P < 0.001) and from the onset of the patient's symptoms (P = 0.003) was worse among women with longer delays. Ten years after the onset of symptoms, survival was 52% for women with delays less than 12 weeks and 47% for those with longer delays. At 20 years the survival rates were 34% and 24% respectively. Furthermore, patients with delays of 12-26 weeks had significantly worse survival rates than those with delays of less than 12 weeks. Multivariate analyses indicated that the adverse impact of delay in presentation on survival was attributable to an association between longer delays and more advanced stage. However, within individual stages, longer delay had no adverse impact on survival. Analyses based on 'total delay (i.e. the interval between a patient first noticing symptoms and starting treatment) yielded very similar results in terms of survival to those based on delay to first hospital visit (delay in presentation).

Adult↗
PubMed1999

Overexpression of c-erbB2 is an independent marker of resistance to endocrine therapy in advanced breast cancer.

The present study investigated the interaction between c-erbB2 overexpression and the response to first-line endocrine therapy in patients with advanced breast cancer. The primary tumours of 241 patients who were treated at first relapse with endocrine therapy were assessed for overexpression of c-erbB2 by immunohistochemistry. c-erbB2 was overexpressed in 76 (32%) of primary breast cancers and did not correlate with any other prognostic factor. The overall response to treatment and time to progression were significantly lower in patients with c-erbB2-positive tumours compared to those that were c-erbB2-negative (38% vs 56%, P = 0.02; and 4.1 months vs 8.7 months, P < 0.001, respectively). In multivariate analysis, c-erbB2 status was the most significant predictive factor for a short time to progression (P = 0.0009). In patients with ER-positive primary tumours treated at relapse with tamoxifen (n = 170), overexpression of c-erbB2 was associated with a significantly shorter time to progression (5.5 months vs 11.2 months, P < 0.001). In conclusion, overexpression of c-erbB2 in the primary tumour is an independent marker of relative resistance to first-line endocrine therapy in patients with advanced breast cancer. In patients with ER-positive primary tumours, the overexpression of c-erbB2 defines a subgroup less likely to respond to endocrine therapy.

Adult↗
PubMed1998

Doxorubicin pharmacokinetics: the effect of abnormal liver biochemistry tests.

We studied variability in doxorubicin pharmacokinetics in 24 patients with abnormal liver biochemistry tests. Blood samples were collected after the first cycle of single-agent doxorubicin given as an i.v. bolus and plasma levels were measured by high-performance liquid chromatography. The relationship between doxorubicin clearance (dose/AUC) and liver biochemistry tests (AST, bilirubin, albumin, alkaline phosphatase and indocyanine green clearance) was investigated. Patients with a raised bilirubin level had reduced doxorubicin clearance, but there was no clear relationship between the extent of this elevation and the reduction in doxorubicin clearance. Doxorubicin clearance was lower in patients with an isolated increase in AST than in those with normal liver biochemistry, but this difference was not statistically significant. Nevertheless, there was a significant correlation between reduced doxorubicin clearance and both raised serum AST levels and low indocyanine green clearance. These pharmacokinetic data suggest that current dose reductions based solely on the extent to which bilirubin is elevated may not be optimal.

Adult↗
PubMed1998

A randomised phase II study of oral pamidronate for the treatment of bone metastases from breast cancer.

47 patients with progressive, painful, predominantly lytic bone metastases from breast cancer were included in a randomised double-blind phase II trial comparing the effects of pamidronate 150 and 300 mg daily. Oral pamidronate produced either sclerosis or stabilisation of lytic metastases for at least 24 weeks in 5 of 24 and 3 of 23 patients at the 300 and 150 mg dose levels, respectively. Evidence of symptomatic improvement was observed in 5 of 22 (23%) and 7 of 22 (32%) patients for symptomatic disease at the respective doses. These improvements were accompanied by a reduction in the rate of bone resorption as shown by suppression (P = < 0.01) of urinary calcium and a non-significant fall in deoxypyridinoline. No obvious differences in efficacy were observed between the two dose levels. Gastrointestinal adverse events, principally comprising nausea and vomiting, were the most commonly reported side-effects leading to discontinuation of trial treatment in 4 of 24 and 2 of 23 patients at 300 and 150 mg dose levels, respectively. The poor tolerability of oral pamidronate coupled with the modest clinical effects reported here suggest that oral pamidronate will not replace the current strategy of regular intravenous infusions of pamidronate for the treatment of osteolytic bone disease.

Administration, Oral↗
PubMed1998

Time trends in breast cancer survival: experience in a single centre, 1975-89.

The aim of this retrospective cohort study was to investigate whether survival of patients with breast cancer has changed over the period 1975-89. A total of 2604 women diagnosed as having invasive breast cancer at a clinical oncology unit in London were followed up for between 5 and 20 years. Patients were divided into four groups according to menstrual status (pre or post) and the staging of cancer (operable or inoperable). For each group, survival from diagnosis was compared between three consecutive 5-year cohorts, both with and without adjustments made for relevant prognostic factors. No temporal patterns were found in patients with inoperable cancer, in whom the survival rate was consistently low. Of women with operable cancers, differences were seen only among post-menopausal women, for whom the best survival patterns were seen in patients diagnosed between 1985-89. This is probably due to tamoxifen being commonly prescribed as adjuvant treatment for this cohort of patients. We cannot explain an apparently worse survival in the group of patients presenting in the early 1980s compared with that observed in the late 1970s.

Adult↗
PubMed1998

Family history and survival in premenopausal breast cancer.

The clinicopathological characteristics of breast cancer in 95 women between the ages of 24 and 45 years with a family history of breast cancer were compared with tumours from 329 women with sporadic disease matched for age and year of diagnosis. There was a trend for the family history patients to have slightly smaller tumours (mean size 2.49 cm) than the controls (mean 3.04 cm) (Mann-Whitney test, P = 0.09). A significantly greater proportion of the familial cases had grade III infiltrating ductal carcinoma than did the controls (40% vs 27%; chi2(1) = 5.64, P = 0.02). Despite this, there were more cases of operable node-negative disease among the study group than among the controls (48% vs 32%; chi2(1) = 8.2, P = 0.004). There was a highly significant survival advantage for patients with a family history (chi2 = 22.4, P < 0.001). Five- and 10-year survival rates were 92% and 87% for those with a family history compared with 70% and 54% for those in the control group. This survival advantage was maintained when patients with operable disease only were considered. In multivariate analysis, which included age, tumour size, stage, histological grade and family history, family history was an independent predictor of favourable prognosis and, in a Cox model, was associated with a relative risk of survival of 6.11 (95% CI 2.81-13.28). These results suggest that familial breast cancer has a more favourable clinical course than the more common sporadic forms of the disease.

Adult↗
PubMed1998

Clinical course and prognostic factors following bone recurrence from breast cancer.

Three hundred and sixty-seven women presenting to the Breast Unit at Guy's Hospital between 1975 and 1990 whose first distant metastasis was in the skeleton were identified and the influence of a number of patient and tumour characteristics on the development and subsequent prognosis of bone metastases was assessed. One hundred and thirty-nine women had disease that remained clinically confined to the skeleton. They were more likely to be older, with lobular carcinoma and to have presented initially with little or no axillary lymph node involvement. The 228 women who subsequently developed disease at extra-osseus sites were more likely to have poorly differentiated ductal tumours and heavy lymph node involvement at primary diagnosis. On multivariate analysis, the clinical and pathological factors of greatest prognostic importance for survival after the development of bone metastases were histological grade (P = < 0.0001), oestrogen receptor status (P = < 0.0001), bone disease at initial presentation (P = < 0.0001), disease-free interval (P = 0.002) and age (P = 0.006).

Adult↗
PubMed1998

Do patients with advanced breast cancer benefit from chemotherapy?

This study aimed to assess the proportion of patients with advanced breast cancer who report benefit from first-line palliative chemotherapy using a simple global measure of wellbeing and to identify factors predicting benefit. A consecutive series of women with advanced breast cancer undergoing first-line palliative chemotherapy was evaluated. The main outcome measure was patient report of overall wellbeing assessed at post-treatment interview. Physical, psychological and functional status were assessed using the Rotterdam Symptom Checklist (RSCL) on three occasions (pretreatment, at the start of the third cycle and post treatment). It was planned that treatment would be discontinued after six cycles (i.e. 18-24 weeks). One hundred and sixty patients started treatment, of whom 155 were assessable for quality of life. After treatment, 41 (26%) patients reported they felt better, 29 (19%) felt the same and 34 (22%) felt worse than they did before treatment. The other 51 (33%) patients either died or stopped attending the hospital before the post-treatment interview and were assigned as treatment 'failures'. Patients who reported feeling better after treatment had improvements in psychological distress (P < 0.0001), pain (P = 0.01), lack of energy (P = 0.02) and tiredness (P = 0.02), as well as improvement in functional status (P = 0.07). Feeling better was also correlated with disease response (P = 0.03). Feeling worse after treatment or treatment 'failure' was predicted by the pretreatment presence of a dry mouth (P = 0.003) and high levels of psychological distress (P = 0.03). Pretreatment lack of energy (P = 0.01), dry mouth (P = 0.02), presence of liver metastases (P = 0.03) and breathlessness (P = 0.03) predicted treatment 'failures'. The results of this study suggest that first-line palliative chemotherapy for advanced breast cancer confers benefit on a substantial proportion of patients, with about one-quarter feeling better after treatment and nearly a half feeling better or the same some 4-6 months after the start of treatment. Factors identified in this study may assist clinicians in deciding which patients should not be offered treatment, because of high risk of feeling worse or treatment 'failure'. This work now needs to be validated on a further cohort of women receiving chemotherapy for advanced breast cancer.

Adult↗
PubMed1998

Current use of bisphosphonates in oncology. International Bone and Cancer Study Group.

PURPOSE: The purpose of this article is to review the recent data on bisphosphonate use in oncology and to provide some guidelines on the indications for their use in cancer patients. DESIGN: The group consensus reached by experts on the rationale for the use of bisphosphonates in cancer patients and their current indications for the treatment of tumor-induced hypercalcemia and metastatic bone pain in advanced disease and for the prevention of the complications of multiple myeloma and of metastatic bone disease are reviewed. RESULTS: Bisphosphonates are potent inhibitors of tumor-induced osteoclast-mediated bone resorption. They now constitute the standard treatment for cancer hypercalcemia, for which we recommend a dose of 1,500 mg of clodronate or 90 mg of pamidronate; the latter compound is more potent and has a longer lasting effect. Intravenous bisphosphonates exert clinically relevant analgesic effects in patients with metastatic bone pain. Regular pamidronate infusions can also achieve a partial objective response by conventional International Union Against Cancer criteria and enhance the objective response rate to chemotherapy. In breast cancer, the prolonged administration of oral clodronate 1,600 mg daily reduces the frequency of morbid skeletal events by more than one fourth, whereas monthly pamidronate infusions of 90 mg for only 1 year in addition to chemotherapy reduce by more than one third the frequency of all skeletal-related events. The use of bisphosphonates to prevent bone metastases remains experimental. Last, bisphosphonates in addition to chemotherapy are superior to chemotherapy alone in patients with stages II and III multiple myeloma and can reduce the skeletal morbidity rate by approximately one half. CONCLUSION: Bisphosphonate use is a major therapeutic advance in the management of the skeletal morbidity caused by metastatic breast cancer or multiple myeloma, although many questions remain unanswered, notably regarding the optimal selection of patients and the duration of treatment.

Analgesics, Non-Narcotic↗