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Biomedical subjects

R D Rubens

Publications and source records attributed to R D Rubens.

At least 109 records · Page 6Linked to original sources
PubMed1990

Adjuvant cyclophosphamide, methotrexate, and fluorouracil in patients with axillary node-positive breast cancer: an update of the Guy's/Manchester trial.

Between 1976 and 1985, 391 patients (202 premenopausal, 189 postmenopausal) with operable breast cancer and positive axillary lymph nodes were randomized after total mastectomy and axillary clearance to receive cyclophosphamide, methotrexate, and fluorouracil (CMF) (n = 193) or no adjuvant therapy (n = 198). After a median follow-up of 8 years, both relapse-free survival (RFS) and survival (S) were significantly prolonged in premenopausal patients receiving CMF (RFS, P less than .001; S, P = .003). Treatment with CMF resulted in a significant improvement in RFS in premenopausal patients both with steroid receptor-positive and steroid receptor-negative tumors and also in subgroups of premenopausal patients defined by the number of axillary nodes involved. Premenopausal patients who developed permanent amenorrhea following CMF had a significantly better RFS than those who continued to menstruate. Induction of amenorrhea following CMF was related to age, with almost all patients over 40 years becoming amenorrheic. For patients less than or equal to 40 years, development of amenorrhea following CMF did not influence outcome. No difference was detected between control and CMF groups (RFS, P = .9; S, P = .9) in postmenopausal patients nor in any subgroup of these patients. The results of this trial of the efficacy of CMF for improving RFS and S have strengthened with longer follow-up.

Adult↗
PubMed1990

Node-negative breast cancer: prognostic subgroups defined by tumor size and flow cytometry.

Adjuvant systemic therapy for women with node-negative breast cancer is most easily justified for those patients at highest risk of relapse. We have examined the impact of tumor size, histologic grade, estrogen receptor (ER) status, tumor ploidy, and S-phase fraction (SPF) on relapse-free survival (RFS) for 169 patients with node-negative breast cancer in order to identify groups of patients at high and low risk of relapse. Patients with small tumors (less than or equal to 1.0 cm) had a significantly better RFS than those with larger tumors (P = .005), with 96% remaining relapse-free at 5 years. Patients with tumors less than or equal to 1.0 cm were thus excluded from analysis when attempting to define a group with a poor prognosis. Within the group of patients with tumors greater than 1.0 cm, tumor ploidy (P = .63), ER status (P = .3), or progesterone receptor (PgR) status (P = .24) did not predict for RFS. Patients with grade 1 or 2 infiltrating ductal tumors had a significantly better prognosis than those with grade 3 tumors (P = .04). The prognostic factor that gave the widest separation between subgroups, however, was SPF. Patients whose tumors were greater than 1.0 cm with an SPF less than or equal to 10% had a 5-year RFS of 78% compared with a 5-year RFS of 52% for those with an SPF greater than 10% (P = .006). We have combined tumor size and SPF to identify three prognostic groups: (1) tumor less than or equal to 1.0 cm, 5-year RFS 96%; (2) tumor greater than 1.0 cm plus SPF less than or equal to 10%, 5-year RFS 78%; 3) tumor greater than 1.0 cm plus SPF greater than 10%, 5-year RFS 52%. These prognostic groupings may help identify patients most suitable for adjuvant therapy.

Breast Neoplasms↗
PubMed1989

Stress and relapse of breast cancer.

To elucidate the association between stressful life events and the development of cancer the influence of life stress on relapse in operable breast cancer was examined in matched pairs of women in a case-control study. Adverse life events and difficulties occurring during the postoperative disease free interval were recorded in 50 women who had developed their first recurrence of operable breast cancer and during equivalent follow up times in 50 women with operable breast cancer in remission. The cases and controls were matched for the main physical and pathological factors known to be prognostic in breast cancer and sociodemographic variables that influence the frequency of life events and difficulties. Severely threatening life events and difficulties were significantly associated with the first recurrence of breast cancer. The relative risk of relapse associated with severe life events was 5.67 (95% confidence interval 1.57 to 37.20), and the relative risk associated with severe difficulties was 4.75 (1.58 to 19.20). Life events and difficulties not rated as severe were not related to relapse. Experiencing a non-severe life event was associated with a relative risk of 2.0 (0.62 to 7.47), and experiencing a non-severe difficulty was associated with a relative risk of 1.13 (0.38 to 3.35). These results suggest a prognostic association between severe life stressors and recurrence of breast cancer, but a larger prospective study is needed for confirmation.

Adult↗
PubMed1989

Comparison of intracavitary bleomycin and talc for control of pleural effusions secondary to carcinoma of the breast.

In a prospective randomized study, patients with pleural effusions secondary to breast carcinoma were randomly allocated to be treated by pleurodesis using either intracavitary talc or bleomycin. For 25 assessable treatments in 22 patients, recurrence of effusion was observed in 5 of 15 (33 per cent) of the bleomycin group compared with none in the talc group. It is concluded that talc is superior to bleomycin in controlling pleural effusions secondary to breast carcinoma, but bleomycin may have a role in patients unfit for general anaesthesia or with extensive disease elsewhere.

Bleomycin↗
PubMed1989

Phase II study of mitoxantrone for liver metastases from breast cancer.

Mitoxantrone was given to 19 patients with liver metastases from breast cancer and biochemical evidence of liver dysfunction. In all, 2 patients received the drug at a dose of 10 mg/m2 on days 1 and 2 of the first course of treatment; 1 patient was given 9 mg/m2 and 17 received 8 mg/m2. Subsequent courses were given at a dose of 10 mg/m2. Three patients (16%) showed a partial response, with time to progression of between 3 and 7 months. Toxicity was considerable, with myelosuppression being the major problem.

Bone Marrow↗
PubMed1989

Influence of radiotherapy on the dose of adjuvant chemotherapy in early breast cancer.

399 patients with early breast cancer were randomly allocated to treatment by either modified radical mastectomy or lumpectomy and radiotherapy. 169 had histologically involved axillary nodes and were randomised to receive either adjuvant cytotoxic chemotherapy (76 patients) or no systemic adjuvant treatment (93 patients). Chemotherapy comprised a combination of oral cyclophosphamide and intravenous methotrexate and 5-fluorouracil (CMF) for 12 cycles over one year. Patients in the mastectomy group received a significantly higher percentage of the planned chemotherapy dose compared with those in the radiotherapy group (median 85% v. 71% p less than 0.05). Patients treated with radiotherapy were more frequently nauseated and developed more severe alopecia, but these differences were not statistically significant. At median follow-up of 37 months the relapse-rate and pattern of relapse were similar in both groups of patients receiving CMF.

Aged↗
PubMed1989

Locally advanced breast cancer: the contribution of cytotoxic and endocrine treatment to radiotherapy. An EORTC Breast Cancer Co-operative Group Trial (10792).

Patients with locally advanced carcinoma of the breast were randomized to receive either radiotherapy alone, radiotherapy + endocrine therapy, radiotherapy + chemotherapy or radiotherapy + endocrine therapy + chemotherapy. In 363 evaluable patients, time to first progression was delayed significantly by both endocrine treatment and chemotherapy, the greatest effect being achieved by the combination of endocrine treatment and chemotherapy. This effect was almost entirely due to a major effect of systemic treatment on time to loco-regional progression, for which the result is highly significant, rather than time to distant metastasis in which only a non-significant trend was observed. For survival, a trend was seen in favour of the combination of hormone treatment and chemotherapy, but this effect did not achieve statistical significance. This trial suggests that current endocrine and cytotoxic treatments are only of marginal value in improving the prognosis in locally advanced breast cancer.

Adult↗
PubMed1989

Weekly epirubicin for breast cancer with liver metastases and abnormal liver biochemistry.

Thirty-six consecutive patients with breast cancer and liver metastases with abnormal liver biochemistry were treated with epirubicin 25 mg m-2 i.v. weekly. No dose modification was made for abnormal liver biochemistry, but dose intensity was adjusted by delaying treatment according to myelosuppression. The UICC overall response rate according to UICC criteria was 11/36 (30%) and median response duration was 27 weeks. Liver biochemistry improved in a further seven patients. Treatment was well tolerated. Epirubicin given in this way is effective in patients with breast cancer and liver metastases. An initial deterioration in liver biochemistry may occur before there is a response to epirubicin.

Adult↗
PubMed1989

Management of advanced breast cancer.

The systemic treatment of advanced breast cancer is not curative in intent but steady progress is being made which should lessen the morbidity from metastatic disease. Reference has been made to relevant posters presented at the International Symposium on Endocrine Therapy.

Breast Neoplasms↗
PubMed1988

Effects of prednisolone on sex hormone binding globulin during primary endocrine treatment of advanced breast cancer.

Serum sex hormone binding globulin (SHBG) was measured in 21 pre and 39 postmenopausal women with advanced breast cancer before treatment and 1, 3, 6, 9 and 12 months after ovarian irradiation or during continuous administration of tamoxifen at a dose of 10 mg twice daily, respectively; some patients received additional prednisolone at a dose of 5 mg twice a day. Ovarian irradiation was associated with a 25% reduction in serum SHBG levels 3 to 6 months after treatment whilst patients on tamoxifen experienced a rise of about 80% in serum SHBG levels after 1 to 3 months. In postmenopausal women prednisolone markedly dampened the effect of tamoxifen, reducing a 80% rise to about 20%. There was no relationship between SHBG levels and response to treatment.

Breast Neoplasms↗
PubMed1988

Osteocalcin: a potential marker of metastatic bone disease and response to treatment.

Serum osteocalcin (BGP) is an osteoblast product that probably reflects the rate of bone formation. It is a potential marker of skeletal metastases and, to investigate this, BGP was measured by radioimmunoassay in the serum of normal subjects and patients with breast or prostate cancer. Significantly higher levels were found in patients with metastatic bone disease in comparison to both normal subjects (P less than 0.001) and patients with non-metastatic cancer (P less than 0.05 for breast cancer and less than 0.001 for prostate cancer). The range of values was wide. Levels were higher in sclerotic than lytic bone metastases (P less than 0.01) and lower in patients with hypercalcaemia (P less than 0.001). Serial measurements of BGP were made in 53 patients with skeletal metastases from breast cancer receiving systemic therapy. At 1 month BGP rose by greater than 0.5 ng/ml in 15/16 responding patients compared with 7/23 patients with progressive disease (P less than 0.01). Responding patients also showed a rise in the bone isoenzyme of alkaline phosphatase and a paradoxical deterioration in the bone scan appearance, both reflecting a flare in osteoblast activity. The early increase in responding patients was followed by a gradual decrease over subsequent months as the osteoblast reaction induced by systemic therapy subsided. We conclude that BGP measurements reflect a wide variability of bone formation rates in metastatic bone disease. Bone formation was usually increased, particularly when metastases were sclerotic in appearance, but in patients with hypercalcaemia the low BGP levels suggest uncoupling of bone resorption and formation. Serial measurements of BGP may be useful in monitoring response to treatment.

Biomarkers, Tumor↗
PubMed1988

Biochemical prediction of response of bone metastases to treatment.

Assessment of response of skeletal metastases to systemic therapy is currently dependent on radiological evidence of bone healing. We have performed a prospective study of additional response criteria in patients with progressive bone metastases from breast cancer. Changes in these potential markers of response were correlated with the radiological response and the time to treatment failure (TTF). Successful systemic therapy typically led to a transient increase in osteoblast activity ('flare'), a reduction in osteoclast activity and symptomatic improvement. After 1 month a greater than 10% rise in serum osteocalcin (BGP) and alkaline phosphatase bone isoenzyme (ALP-BI) and a greater than 10% fall in urinary calcium excretion were seen in 14/16 patients with radiographic evidence of bone healing (UICC partial responders). In comparison similar biochemical changes at 1 month were seen in only 4/20 patients with progressive disease (P less than 0.001). The predictive value and diagnostic efficiency (DE) of changes at 1 month in biochemical measurements and symptom score has been calculated. The combination of a greater than 10% rise in ALPBI and BGP and a greater than 10% fall in urinary calcium excretion had a DE of 89% for discriminating response from progression, 88% for response from non-response (progressing + no change patients), and 76% for TTF of greater than 6 months from TTF of less than 6 months. Serum calcium, tartrate resistant acid phosphatase (TRP), urinary hydroxyproline excretion and bone scan changes were unhelpful in discriminating between patient groups. Independent confirmation is needed, but our results suggest there are reliable alternatives to plain radiography in the early assessment of response of bone metastases to treatment.

Adult↗
PubMed1988

Treatment of bone metastases from breast cancer with (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD).

Twenty-eight patients with progressive symptomatic bone metastases from breast cancer received (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) 30 mg in 500 ml of 0.9% saline infused over 2 h every 14 days. No other systemic therapy for breast cancer was prescribed. All patients had progressed on at least one previous systemic treatment. APD was continued until the disease progressed. Patients were assessed for objective response by the UICC criteria. In addition, subjective response was determined by a pain questionnaire. Radiological evidence of bone healing with sclerosis of lytic disease (UICC partial response) was seen in 4 patients. The median duration of response was 10 months. Eleven patients had stable disease for at least 3 months (median 5 months) and 9 progressed. Symptomatic response occurred in 9 patients and 12 reported an improvement in quality of life. Treatment was tolerated well with no significant toxicity. In conclusion, long-term inhibition of bone destruction is possible with APD therapy alone and both subjective and objective responses are seen.

Adult↗
PubMed1988

Prednisolone improves the response to primary endocrine treatment for advanced breast cancer.

Two hundred and twenty patients with progressive advanced breast cancer were given primary endocrine treatment (PET) according to menstrual status. Pre-menopausal patients received ovarian irradiation (O) and post-menopausal tamoxifen 10 mg bd (T). Patients were randomised to receive either no additional treatment or prednisolone 5 mg bd (P). Similar results were observed in each menstrual subgroup. In 194 evaluable patients, the response to PET + P was 49% and to PET alone 30% (P less than 0.01). P increased the median duration of response from 9 to 14 months (P less than 0.002) and the median time to disease progression from 5 to 9 months (P less than 0.001). Response to P after O or T alone occurred in only 2/62 (3%). Median survival in patients randomised to receive P at the outset of PET was prolonged by 4 months (P less than 0.05). The addition of P significantly improves the response to O or T in the treatment of advanced breast cancer.

Adult↗