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Biomedical subjects

R D Rubens

Publications and source records attributed to R D Rubens.

At least 145 records · Page 8Linked to original sources

A trial of human alpha interferon as an adjuvant agent in breast cancer after loco-regional recurrence.

Thirty-two women who had developed loco-regional recurrence of breast carcinoma were entered into a controlled trial of adjuvant alpha-interferon. All patients had histological confirmation of recurrence, local treatment with radiotherapy and negative staging investigations. They were then randomized to either observation alone, or treatment with human alpha interferon 3 x 10(6) units subcutaneously daily for 1 year. There were no differences detected in the rate of local or distant relapse. With this lack of clinically significant efficacy and a high incidence of side effects, it is concluded that alpha interferon is of doubtful value in the adjuvant treatment of breast cancer.

Adjuvants, Immunologic↗

Mechanism of action of adjuvant chemotherapy in early breast cancer.

The relation between tumour oestrogen and progesterone receptor status, menstrual status, relapse-free survival, and overall survival was analysed in 411 patients with early breast cancer randomised to receive either postoperative adjuvant chemotherapy with cyclophosphamide, methotrexate, and fluorouracil (CMF) or no additional treatment (control). Prolongation of time to recurrence and survival was seen predominantly in premenopausal patients; these effects were seen only with tumours positive for steroid receptors, particularly progesterone. Chemotherapy led to permanent amenorrhoea in 61% of premenopausal patients. The therapeutic effects of chemotherapy were seen only when CMF induced permanent amenorrhoea in premenopausal patients. These findings support the hypothesis that the effect of adjuvant chemotherapy in early breast cancer may be mediated by ovarian suppression.

Adult↗

The activity of phosphohexose isomerase in primary breast carcinomas and response to chemotherapy in patients with metastatic disease.

The activity of phosphohexose isomerase [PHI] was measured in 48 primary carcinomas from patients with breast cancer, and its usefulness as a predictor of response to cytotoxic drugs at the metastatic stage was evaluated. There was a statistically significant difference in the activity of PHI between responders and non-responders to these treatments. These preliminary findings are currently being evaluated in an extended series.

Antineoplastic Agents↗

Response to endocrine therapy and breast cancer differentiation.

The purpose of this study was to determine whether aspects of tumour differentiation are associated with response to endocrine therapy in patients with advanced breast cancer. The features studied were the histological type, grade, and elastosis content of the primary tumours, and the disease-free interval. Statistically significant associations were observed between response to endocrine therapy and histological grade and disease-free interval. In addition, statistically significant associations were observed between histological grade and elastosis and disease-free interval. It is concluded that tumours which are more highly differentiated have a better chance of responding to endocrine therapy.

Androgens↗

A comparison of intracavitary talc and tetracycline for the control of pleural effusions secondary to breast cancer.

Forty-one patients with malignant pleural effusions secondary to breast cancer were randomly allocated to treatment with either intracavitary talc or intracavitary tetracycline. Of 33 evaluable patients, radiological control was achieved in 11/12 (92%) of the talc group compared with 10/21 (48%) of the tetracycline group (P = 0.022). Intracavitary talc provides effective palliation of metastatic pleural effusions secondary to breast cancer.

Breast Neoplasms↗

Serum prolactin levels in women with breast cancer and their relationship to survival.

Serum prolactin (HPr) has been measured in 459 patients 1 day before (HPr-1) and in 433 patients 10 days after (HPr-2) treatment. These came from an unselected sequence of 739 patients with operable breast cancer who had been referred to Guy's Hospital over a period of 5 yr. In addition HPr was measured in 100, or more, women at 3, 6 or 12 months after mastectomy. The median levels of either HPr-1 or HPr-2 were higher in pre-menopausal compared with postmenopausal patients (P = 0.03 and 0.06, respectively). Mastectomy was associated with increased serum HPr in both pre- and post-menopausal patients (P less than 0.001 in both cases). Average levels at 3 months, or after, were similar to those found before treatment. Nulliparous women had a higher median amount of HPr-1 than parous which was significant in premenopausal patients (P less than 0.008) whilst HPr-2 levels were not related to parity. Thus the rise in HPr associated with surgery was greater in parous than nulliparous women. Prolactin levels were not related to nodal status or tumour size. However, the amounts of HPR-2 were significantly greater in women with histological grade 3 tumours than those with grade 1 or 2. Standardising for either nodal status, tumour size or histological grade seven situations were found in which HPr-1 or HPr-2 levels were of prognostic significance. Although some of these significant associations could be fortuitous all shared a common feature that the least favourable prognosis was associated with the highest HPr levels.

Adult↗

Histochemical studies with an estrogen receptor-related protein in human breast tumors.

The histochemical characteristics of a Mr 29,000 phosphoprotein related to estradiol receptor are described in a large series of human breast tumors. The antigen was detected with a monoclonal antibody (D5) raised against partially purified human myometrial estradiol receptor. An indirect immunoperoxidase method was used with methacarn-fixed, wax-embedded sections. Quantitation of staining and its reproducibility are described. Results with trucut biopsies agree with those obtained with larger tumor sections. Normal breast is infrequently positive. Histochemical staining is higher in invasive carcinoma than in normal breast with ductal carcinoma in situ adjacent to infiltrating tumors exhibiting intermediate values. Furthermore, most in situ carcinomas have a heterogeneous staining pattern. About 20% of invasive tumors also exhibit heterogeneity. No simple correlation is seen between staining and histological grade. There are more low-staining tumors in young (less than 50 yr old) patients than in older women. Staining correlates with levels of cytosol estradiol receptor but not cytosol progesterone receptor. However, cytosol estradiol receptor-negative, cytosol progesterone receptor-positive tumors tend to have positive Mr 29,000 phosphoprotein levels. Positive staining is associated with a higher response rate to hormone therapy (50%). None of the negative tumors responded to hormone treatment. With these patients, comparison of histochemical assay for Mr 29,000 phosphoprotein and [3H]estradiol binding assays indicated that the former was at least as good as the latter assay in predicting hormone response. About 20% of cytosol estradiol receptor-positive tumors have low Mr 29,000 phosphoprotein, and such tumors have poor response to hormone treatment.

Adult↗

Influence of reproductive history on age at diagnosis of breast cancer and prognosis.

The effect on age at breast cancer diagnosis of age at menarche, age at first baby, parity and age at menopause has been determined for 739 unselected patients diagnosed between 1975 and 1980 as having operable breast cancer. Age at diagnosis was significantly and positively associated with ages at menarche, first baby and menopause. The average number of children significantly declined with increasing age at diagnosis. This was largely due to a change in the proportion of patients who were nulliparous (15% in women aged 41-50 years compared to about 30% in those over 60 years). A group of 1,989 normal women whose reproductive history was also collected between 1975 and 1980 showed similar trends between age and age at menarche, age at first baby and parity as the patients. Thus it appears that these reproductive parameters do not alter the time of onset of breast cancer but could be explained by temporal changes in reproductive patterns. There was no significant correlation between age at menopause and age at diagnosis for patients whose age at menopause was no more than 54 years and age at diagnosis no less than 55 years, respectively. It is therefore unlikely that age at menopause affects age at diagnosis. Postmenopausal patients with 3 or more children had a significantly shorter disease-free interval and lower survival rate than those with less children. None of the other parameters was associated with prognosis.

Adult↗

Mitomycin C and vinblastine in the treatment of advanced breast cancer.

Forty-nine women with progressive metastatic breast cancer, extensively pretreated, received mitomycin C 12 mg/m2 and vinblastine 6 mg/m2 intravenously every 3 weeks. Eleven patients responded, giving a response frequency of 22%. Considering only the 40 patients evaluable after two or more courses of treatment, the response frequency is 27.5%. Responses occurred predominantly at soft tissue sites. Subjective toxicity was mild.

Adult↗

Recombinant DNA human interferon alpha 2 in advanced breast cancer: a phase 2 trial.

Effectiveness of recombinant DNA (rDNA) human interferon alpha 2 (IFN alpha 2) in advanced breast cancer was evaluated in 14 patients who had received prior endocrine and/or cytotoxic therapy. After randomization, 7 patients received IFN alpha 2 two million IU m-2 day-1, s.c., 3 times a week (schedule 1) and 7 patients received 50 million IU m-2 day-1, i.v., for 5 consecutive days, every 3 weeks (schedule 2). Treatment duration was 4-21 weeks in schedule 1 and 6-24 weeks (2-8 courses) in schedule 2. Regressions were not achieved with either schedule. Treatment was associated with significant toxicity and was more severe in schedule 2. Dose limiting toxicities were leukopenia, elevation of liver enzymes, hyperglycemia and fatigue. Serum IFN activity was low or undetectable in patients on schedule 1 and high in patients on schedule 2. At 24 h, serum IFN activity was detectable in only 1/6 patients on schedule 1 as compared to 3/7 patients on schedule 2. IFN neutralizing factors were detected in the serum of only 1 patient prior to treatment but none were detected in any of the patients during or after discontinuation of treatment (4-24 weeks). IFN alpha 2 increased the expression of both HLA class 1 antigens and beta 2 microglobulin in peripheral blood lymphocytes in vivo. This effect was dose related.

Adult↗

Single-dose etoposide in combination with vincristine and doxorubicin in the treatment of small-cell lung cancer (SCLC).

From July 1980, 104 consecutive patients with previously untreated small-cell lung cancer (SCLC) received vincristine 1.4 mg/m2, doxorubicin (Adriamycin) 40 mg/m2, and Etoposide (VePesid) 300 mg/m2 intravenously (as a single infusion) every 3 weeks. The overall response rate (complete response plus partial response) was 58%. In 47 patients with limited disease the response rate was 66% with 21/47 (45%) complete responders. Treatment was delivered on an outpatient basis. Toxicity was mild, and in 455 rapid infusions of etoposide, there have been no adverse reactions.

Adult↗

Deoxyribonucleic acid (DNA) content of primary carcinoma and response to endocrine or cytotoxic drug therapies in patients with advanced breast cancer.

The DNA content of primary carcinomas was estimated colorimetrically in 111 patients with carcinoma of the breast who subsequently developed metastatic disease. The data were analysed to investigate whether these measurements will assist clinicians in predicting: survival from mastectomy or recurrence, the likelihood of response to the first endocrine or the first cytotoxic drug therapy, duration of response amongst responders to these treatments, and time to treatment failure (TTTF). The DNA content of primary carcinomas failed to predict the clinical course of the disease for patients who underwent endocrine treatments. In patients who were treated by cytotoxic drug therapies, only the duration of response amongst responders to these therapies was significantly shorter in cases where the DNA content was high. The DNA content of carcinomas failed to give any useful information on other parameters. It is concluded that these measurements are unlikely to be of prognostic value in these cases.

Antineoplastic Combined Chemotherapy Protocols↗