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Biomedical subjects

D C Tormey

Publications and source records attributed to D C Tormey.

At least 145 records · Page 8Linked to original sources
PubMed1978

A randomized comparative trial of adriamycin versus methotrexate in combination drug therapy.

A prospective randomized trial was conducted comparing the clinical response of 78 previously untreated patients with advanced metastatic breast cancer to a combination of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) or to a combination of cyclophosphamide, adriamycin, and 5-fluorouracil (CAF). Sixty-two percent of the patients receiving CMF responded to treatment compared to an 82% response rate for the patients receiving CAF. Although within acceptable limits, hematologic and GI toxicity was greater with CAF. There was no significant difference in the duration of response to the two regimens. Therefore, the therapeutic difference between the two therapies is a higher initial response rate to the adriamycin containing regimen.

Breast Neoplasms↗
PubMed1978

A quantitative approach to determining disease response during therapy using multiple biologic markers: application to carcinoma of the breast.

This analytical study was undertaken in an effort to develop a model for a quantitative approach to the evaluation of multiple biological marker levels in blood and urine as a means for determining tumor changes during treatment of patients with malignant disease. The potential biologic markers measured in patients with carcinoma of the breast consist of three urinary polyamines (putrescine, spermidine and spermine), three urinary nucleosides (pseudouridine, N2, N2-dimethylguanosine and 1-methylinosine), and plasma carcinoembryonic antigen (CEA). The distribution patterns of the seven markers measured pretreatment and five weeks after initiating therapy were examined by grouping the patients into the three categories of progression, stable, or regression based on their clinical response to treatment. In addition to the individual marker measurements, the pretreatment and posttreatment values of the ratios of the polyamine levels (spermine/putrescine, spermine/spermidine, and spermidine/putrescine) and the nucleoside levels (N2, N2-dimethylguanosine/pseudouridine, 1-methylinosine/pseudouridine, and 1-methylinosine/N2, N2-dimethylguanosine) were also evaluated. In the pretreatment measurements, CEA levels were elevated for 76% of the patients and the three nucleosides were elevated for 36% of the patients and the three nucleosides were elevated for 36% to 37% of the patients. Urinary spermidine and spermine levels were abnormal for 27% and 24%, respectively, while putrescine levels were elevated for 7% of the patients. When all 14 marker measurements and the 12 ratios of these measurements were considered, the multiple regression equation evaluated the treatment results with a multiple correlation coefficient (R = 0.891; P less than 0.100) about 2.4 times higher than with the most sensitive single marker variable, N2, N2-dimethylguanosine/pseudouridine (R = 0.377; P less than 0.05), alone. Stepwise regression analysis revealed that the minimum number of multiple marker measurements and their ratios required to achieve the maximum value of the multiple correlation coefficient (R = 0.653; p = 0.010) was fifteen. These include the pre and posttreatment measurements of CEA, spermine, N2, N2-dimethylguanosine and 1-methylinosine, as well as two ratios of the polyamines and three ratios of the nucleosides in the post-treatment of the polyamines and three ratios of the nucleosides in the post-treatment measurements. These data suggest that the utilization of regression analysis to evaluate the monitoring utility of multiple marker measurements may be of clinical value.

Breast Neoplasms↗
PubMed1978

Biologic markers in breast carcinoma. IV. Serum fucose-protein ratio. Comparisons with carcinoembryonic antigen and human chorionic gonadotrophin.

Serum fucose-protein ratio was evaluated as a potential biologic marker for patients with metastatic breast cancer. By analysis of the same blood samples, comparisons were made with carcinoembryonic antigen (CEA) and human chorionic gonadotrophin (hCG). For 150 patients with metastatic breast cancer, 85% had a value for serum-fucose protein ratio above the normal range in comparison to 75% for CEA and 40% for hCG. Serum fucose-protein ratio was exclusively increased in 12% of the patients, CEA in 4% and hCG in 2%. Both serum-fucose protein ratio and CEA were elevated in 39% of the patients, and together, either in combination of alone, were increased in 93% of the patients. Raised values for serum fucose-protein ratio as well as for CEA decreased with change in disease status from pretreatment to response for patients with measurable disease parameters and increased correspondingly with overt disease progression. Preliminary data indicate both serum fuxose-protein ratio and CEA frequently become elevated when patients progress from a disease free interval after surgery to recurrence.

Breast Neoplasms↗
PubMed1978

Clinical correlation between CEA and breast cancer.

Elevated plasma CEA levels were observed in 14.2% (2/14) of preoperative patients, 7.9% (3/38) of postoperative patients, and 70.9% (83/117) of patients with metastatic disease. Within these respective groups the simultaneous measurement of hCG, three polyamines and three minor nucleosides further enhanced the detection rates to 69.2%, 54.2%, and 98.6%. It was observed that in patients with at least one elevated CEA, measurement of sequential CEA levels paralleled the clinical course of metastatic disease in 25 patients. Prior to therapy for metastatic disease CEA levels greater than 5 ng/ml were associated with lower response rates and a shorter time to treatment failure than were levels less than or equal to 5 ng/ml. This effect was enhanced in patients also having an elevated hCG level. Hepatic and osseous involvement were associated with a greater incidence of CEA elevations than were pulmonary or soft tissue sites of involvement.

Breast Neoplasms↗
PubMed1978

Serum protein-bound carbohydrates for following the course of disease in patients with metastatic breast carcinoma.

Serum protein-bound carbohydrates, L-fucose, sialic acid, D-galactose, and D-mannose, were measured as potential biologic markers in patients with breast cancer with the use of high-resolution anion exchange separation in combination with a sensitive cerate oxidimetric fluorescence detector system. For 22 randomly selected patients with proved metastatic breast cancer, both L-fucose and sialic acid levels were above the normal range in 21 patients (95%). In contrast, D-mannose was increased in the sera of 9 patients (41%), and D-galactose in 6 (27%). By comparison, the level of carcinoembryonic antigen (CEA) was elevated in 14 patients (64%). The levels for serially determined serum protein-bound carbohydrates paralleled objective changes of response or progression in 5 patients with measurable disease. As might be expected, the degree and pattern of elevation for the individual carbohydrates varied for each patient studied. Combinations of serum protein-bound carbohydrates, particularly L-fucose and sialic acid, and, in addition, CEA, appear to have promise as potential biomarkers for following the course of the disease in patients with metastatic breast cancer.

Blood Proteins↗
PubMed1977

Steroid hormone receptors in normal human lymphocytes. Induction of glucocorticoid receptor activity by phytohemagglutinin stimulation.

The presence of specific steroid hormone receptors in human lymphocytes was investigated in unstimulated and phytohemagglutinin-stimulated glass wool column-purified peripheral blood lymphocytes. Specific steroid binding in intact cells was determined by a whole cell competitive binding assay. Non-phytohemagglutinin-stimulated lymphocytes had about 2700 specific glucocorticoid binding sites per cell; phytohemagglutinin stimulation induced a 2 to 3-fold increase in glucocorticoid receptor activity within 16 h of culture. No estrogen, androgen, or progestin binding sites were detected in either unstimulated or phytohemagglutinin-stimulated peripheral blood lymphocytes. Scatchard analysis of glucocorticoid binding was consistent with a single class of receptor sites with a dissociation constant (Kd) of about 5.5 x 10(-9) M (correlation coefficient r = -0.96). Significant competition for radiolabeled dexamethasone binding was not observed with steroids lacking glucocorticoid activity. There was good agreement between relative binding affinities of various steroids to glucocorticoid receptor in lymphocytes and ability of these steroids to inhibit phytohemagglutinin-stimulated thymidine incorporation.

Binding Sites↗
PubMed1977

Bone marrow involvement in breast cancer: effect on response and tolerance to combination chemotherapy.

Forty-three patients with metastatic breast cancer who had not received prior chemotherapy were divided into two groups on the basis of whether or not a bone marrow examination revealed tumor. Both groups were treated with combination chemotherapy regimens and were analyzed with regard to response and toxicity parameters. The positive marrow group had a response rate similar to that of the negative marrow group (67% vs 71%), and a slightly shorter median time to progressive disease (240 vs 258 days) and median duration of remission (213 vs 243 days). The positive marrow group had higher requirements for hematologic support and tended to have more infectious complications. The data suggest that metastatic breast cancer patients with a bone marrow examination revealing tumor, although requiring more supportive care, may be treated as effectively with combination chemotherapy as those patients in whom the marrow examination does not reveal tumor.

Adult↗
PubMed1977

Biological markers in breast carcinoma. II. Clinical correlations with human chorionic gonadotrophin.

Serum hCG levels were measured in female patients with breast carcinoma and examined with respect to the clinical stage of disease, the clinical tumor burden, prognosis, and the organ sites of involvement. Elevated levels were observed in 65/134 (48.5%) patients with metastatic disease, 5/14 (35.7%) patients preoperatively, and in 9/33 (27.2%) N+ patients from one-six months postoperatively. The greatest proportion of elevated values (60.5%) was in patients with one metastatic site of involvement. Although no correlations were demonstrated between the preoperative or postoperative samples and subsequent disease recurrence, it was observed that 4/10 patients who did have a recurrence had preceding hCG elevations. In metastatic disease the level in 13 patients starting with values greater than 5.8 mIU/ml fell with the attainment of a response or rose with therapeutic failure. The hCG level rose from normal to greater than 6.1 mIU/ml in six additional patients that developed progressive disease. A normal hCG level was associated with a 94.5% response rate to combination chemotherapy whereas the response rate with levels greater than 5 mIU/ml was 71.4%. Only hepatic involvement was associated with a disproportionate incidence of elevations, being 63% compared to 42-47% for other sites. Monitoring hCG levels may be of prognostic use in patients being treated with selected chemotherapy programs for metastatic disease. It appears that further studies are warranted to ascertain if these results will extend to additional treatment approaches.

Breast Neoplasms↗
PubMed1977

Biological markers in breast carcinoma. III. Clinical correlations with carcinoembryonic antigen.

Plasma CEA levels were evaluated by radioimmunoassay in patients with breast carcinoma in relation to clinical-pathologic staging, clinical tumor burden, prognosis and organ sites of involvement. Elevated levels were observed in 83/117 (70.9%) patients with metastatic disease, 2/14 preoperative patients and in 3/39 one-six month postoperative patients. Preoperative levels were elevated in two patients; the levels fell to normal after operation. Changes of elevated CEA levels followed the clinical response to therapy in 22/22 metastatic disease patient-trials. The levels decreased with a response in 15 trials and rose with progressive disease or relapse in seven trials. The incidence of CEA elevations and quantitative CEA levels both rose with increasing clinical tumor burden from the postoperative state through the preoperative state to two or more organ sites of metastatic involvement. No relationship was demonstrable among limited samples between preoperative or postoperative CEA levels and prognosis; however, in metastatic disease, pretherapy CEA levels greater than 5 ng/ml were associated with low response rates and early therapeutic failure to chemotherapy. The highest frequency of elevated CEA levels was observed in patients with osseous involvement (79%) and the lowest frequency with skin (52%) and breast (50%) metastases. Liver and osseous disease were also associated with higher mean CEA levels than were other sites of metastatic involvement. CEA levels appear to be elevated in the majority of patients with metastatic disease and be of prognostic importance in metastatic disease. The level in patients with metastatic disease appears to reflect the therapy-associated tumor burden of the host, especially in patients with elevated levels.

Breast Neoplasms↗
PubMed1977

Implications of the 99mTc diphosphonate bone scan on treatment of primary breast cancer.

The 99mTc diphosphonate scan is important in the study of primary breast cancer. The short-term prognosis for scan-positive patients is poor. Serial bone scans provide a safe and reliable prognostic index in patients following mastectomy. By correlating the scan with biochemical tumor markers, a matrix of diagnostic tests may be developed that is capable of identifying high-risk patients who may benefit from systemic therapy.

Bone Neoplasms↗
PubMed1977

Evaluation of adriamycin and dibromodulcitol in metastatic breast carcinoma.

A phase 1 to 2 evaluation of a combination of adriamycin (ADR) and dibromodulcitol (DBD) was performed in patients with progressive, metastatic breast carcinoma. All but one patient had been treated previously with chemotherapy. ADR was given on Day 1 or Days 1 and 8, and DBD was given on Days 1 to 10 of each 21- to 28-day treatment cycle. Side effects were evaluable in 54 patients, and 50 patients were evaluable for therapeutic response. The dose-limiting toxicities were leukopenia and thrombocytopenia. The severity of both toxicities increased as both the ADR and DBD doses increased; however, the effect of increases in DBD dose was much more profound. The mean white blood cell count and platelet nadirs occurred, respectively, on Days 15.3 and 15.9; both nadirs were delayed for 0.6 day by each 30-mg/sq m/day increase in the DBD dose and delayed for 1.7 to 3.9 days using the Day 1, 8 rather than the Day 1 ADR schedule Recovery of the peripheral counts by Day 29 was prolonged by the Day 1, 8 ADR schedule and by increasing the DBD dose. A tolerable dose schedule for previously treated patients was considered to be ADR, 40 mg/sq m on Day 1, and DBD, 135 mg/sq m on Days 1 to 10 repeated every 28 days. Responses were observed in 46% (23 of 50) of the patients. There were 1 complete remission, 19 partial remissions, and 3 improvements. Thirteen patients showed no change and 14 developed progressive disease. There were responses in 13 of 37 (36%) with visceral dominant disease as compared to 7 of 8 (87%) with osseous and 3 of 5 (60%) with soft tissue-dominant disease. There were 22 of 48 (46%) responses in patients previously exposed to alkylating agent therapy. Twnety-two patients had responded and 19 had failed to respond to prior alkylating agent-containing regimens; the response rates to DBD in these groups were respectively, 45 and 42%. The median time to remission was 29 days. The median time to therapeutic failure was 5.1 months for responders, 2.3 months for patients with no change, and 29 days for progressors. The combination of ADR and DBD appears to be an active and well-tolerated program in patients with previously treated metastatic breast carcinoma.

Adult↗
PubMed1977

Casein production by human breast cancer.

Casein was measured in the sera of breast cancer patients, in breast cancer tumors, and in breast cancer cells in long-term tissue culture using a sensitive and specific radioimmunoassay. Levels present in breast cancer sera were not elevated above control values. Eight of forty-seven (17%) of the tumor samples tested were positive for casein, the highest level representing 0.003% of the soluble protein. When seven human breast cancer cell lines were assayed for casein, the results were uniformly negative even under conditions of stimulation by lactogenic hormones. In addition, direct immunoprecipitation of labeled cellular protein supported the negative result of the radioimmunoassay. Thus it appears that casein production is not a common characteristic of most human breast cancers.

Breast Neoplasms↗
PubMed1976

The role of orchiectomy in the management of advanced male breast cancer.

Nine men with advanced carcinoma of the breast were evaluated after orchiectomy at the National Institutes of Health over 19 years. Of patients followed for greater than one year, five had complete remissions, one had a partial remission, and two patients did not respond to orchiectomy. The average disease-free interval was 20 months; the average survival from the time of orchiectomy in those who responded was 55.8 months and in nonresponders was 26.7 months. Orchiectomy appears to be a safe and effective way to produce an objective response and prolong survival in over 50 percent of men with advanced breast cancer.

Adult↗
PubMed1976

Mediastinoscopy: a diagnostic aid in metastatic carcinoma of the breast.

Six patients with metastatic carcinoma of the breast underwent mediastinoscopy to obtain tissue for estrogen receptor analysis and pathologic confirmation of metastatic tumor. The indication for mediastioxcopy was an abnormal mediastinal accumulation of gallium in five patients, only two of whom had an abnormality noted on tomography. All six patients had tumor recovered by mediastinoscopy as demonstrated by pathologic examination and/or estrogen receptor assay, Therefore, the diagnosis of mediastinal metastases in breast cancer may be suggested by either chest roentgenograms, mediastinal tomography, or gallium scintigraphy. Mediastinoscopy is a safe, effective procedure capable of establishing the diagnosis of metastatic carcinoma of the breast and of procuring sufficient tissue for estrogen receptor analysis in patients without more readily accessible sites of metastases.

Adult↗
PubMed1976

Biochemical markers in cancer of the breast.

Currently, one could summarize this area by saying that we appear to be in a situation where three relatively nonspecific tests detect the majority of patients with metastatic disease, as well as those post-operative patients who are at high risk of relapse. The critical test of their utility for segregating those at risk for relapse from those who are not at high risk will need to be done in a highly select subgroup, e.g., N- patients. Two of these tests, CEA and hCG, also appear to be useful indicators for predicting the probability of responding to combination chemotherapy in metastatic disease. The development and further testing of potentially more specific markers to replace or add to the current matrix is now in progress, Casein, which is a product of the milk synthesis pathway of breast tissue, represents a potentially more specific test than any of those studied to date. HENDRICK and FRANCHIMONT, 1974, have found elevated levels in 21 of 26, or 81%, of patients with metastatic disease, and 8 of 11, or 73%, of patients preoperatively. The test may also reflect the tumor burden since the proportion of patients with elevated levels dropped to 41-50% postoperatively. Further results with this marker are awaited with interest. Other tests such as ferritin, hydroxyproline, or the development of tumor antigen associated immunospecific assays could increase both the specificity and sensitivity of the tests utilized in this field of investigation. Injecting the use of both single marker tests and matrix approaches into routine clinical use in the postoperative setting now appears to be ready for more critical testing. Their use in diagnostic or screening settings, which is the ultimate goal, also needs to be evaluated. Finally, from the practising clinician's viewpoint the data in this discussion should be considered preliminary. It constitutes a status report. Although there is evidence that CEA and hCG are prognostic in metastatic disease, and that subclinical disease is detectable, larger and more tightly controlled studies will be necessary before their routine clinical use can be recommended in breast cancer patients.

Breast Neoplasms↗