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D C Tormey

Publications and source records attributed to D C Tormey.

At least 19 recordsLinked to original sources
PubMed1992

Overexpression of HER-2/neu and its relationship with other prognostic factors change during the progression of in situ to invasive breast cancer.

Using permanent-section immunohistochemistry, we investigated the role of HER-2/neu in the development and progression of human breast cancer by measuring its overexpression in a series of hyperplastic (n = 30), dysplastic (n = 15), and malignant neoplastic (n = 708) lesions of ductal epithelium and by evaluating the relationships between overexpression and clinicopathologic features known to have prognostic significance in these lesions. The neoplasms included pure ductal carcinoma in situ (DCIS; n = 59) and infiltrating ductal carcinoma (IDC; n = 649). The latter were all node negative and stratified into IDC combined (n = 237) or not combined (n = 412) with a "significant amount" of DCIS (defined as DCIS greater than or equal to 10% of total tumor cellularity). Overexpression of HER-2/neu was not observed in any of the hyperplastic or dysplastic lesions. In contrast, it was present in 56% of pure DCIS and in 77% of the comedo subtype of this group. Only 15% of IDC overexpressed HER-2/neu. However, the rate of overexpression was significantly higher in the subset of IDC combined with DCIS compared with the subset of IDC not combined with DCIS (22% v 11%, respectively; P less than .0001). These results are consistent with the hypothesis that HER-2/neu plays a more important role in initiation than in progression of ductal carcinomas. They also suggest that overexpression decreases within individual tumors as they evolve from in situ to increasingly invasive lesions or, alternatively, that many invasive carcinomas arise de novo (ie, without progressing through a significant in situ stage) by mechanisms not involving HER-2/neu. In addition, overexpression of HER-2/neu was associated with several poor prognostic features (younger patient age, premenopause, negative estrogen receptor status, negative progesterone receptor status, and high nuclear grade) in the subset of IDC combined with DCIS. With one exception (negative estrogen receptor status) these associations were lost in IDC not combined with DCIS, also suggesting that the role of HER-2/neu changes during the progression of human breast cancer.

Biomarkers, Tumor↗
PubMed1992

Phase II trials of interferons-alpha and -beta in advanced sarcomas.

Interferons (IFNs)-alpha and -beta were administered to patients with metastatic sarcomas in two different Eastern Cooperative Oncology Group studies. In one study, patients received IFN-alpha 2b, 20 million units/m2 i.v. 5 days/week x 4, then 10 million units s.c.t.i.w. In the second study, patients received IFN-beta ser 180 million units t.i.w. Of 87 patients evaluable for response, there were three responses in 64 patients (5%) treated with IFN-alpha-2b and no responses in 23 patients treated with IFN-beta ser. Severe or life-threatening fatigue with decline in performance status complicated treatment of 37% of patients receiving IFN-alpha 2b and 17% of patients receiving IFN-beta ser. Further investigation of IFNs in sarcomas should depend on evidence from preclinical studies demonstrating synergistic effects of IFNs combined with a cytoreductive modality which has proven activity in these malignancies.

Adult↗
PubMed1992

Adjuvant therapy with a doxorubicin regimen and long-term tamoxifen in premenopausal breast cancer patients: an Eastern Cooperative Oncology Group trial.

PURPOSE: A randomized trial was performed in premenopausal postoperative women with ipsilateral axillary node-positive (N+) breast carcinoma and known estrogen receptor (ER) status to assess the efficacy of an Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH)-based induction regimen and 5 or more years of tamoxifen (Tam). PATIENTS AND METHODS: Patients received 12 28-day cycles of cyclophosphamide 100 mg/m2 orally days 1 to 14, methotrexate 40 mg/m2 intravenously (IV) days 1 and 8, fluorouracil 600 mg/m2 IV days 1 and 8, prednisone 40 mg/m2 orally days 1 to 14, and Tam 10 mg orally twice daily (CMFPT), or the same regimen plus halotestin 10 mg orally twice daily (CMFPTH) alternating monthly with 22-day cycles of vinblastine 4.5 mg/m2 IV day 1, Adriamycin 45 mg/m2 IV day 1, thiotepa 12 mg/m2 IV day 1, halotestin, and Tam (ALTER). Prednisone in the ALTER regimen was stopped after the second CMFPTH cycle. After 12 cycles, patients were again randomized to stop or continue Tam. After 5 years, patients on Tam were again randomized to continue or stop Tam; the results from this randomization are still coded. Among 533 analyzed induction cases, 263 received CMFPT and 270 ALTER. Among 396 analyzed maintenance cases, 201 continued Tam and 195 were observed. Pretreatment characteristics were balanced among treatments. The median follow-up times are 5.1 years for induction and 4.1 years for maintenance. RESULTS: The time to relapse (TTR) was superior for the ALTER regimen (P = .04) and for the maintenance Tam (P = .05). Overall survival comparisons between the regimens are not statistically different. A longer TTR was associated with decreasing nodal involvement, ER+ status, and increasing age. The favorable effects of decreasing nodal involvement and ER+ status carried over to survival; a progesterone receptor-positive (PgR+) status and decreasing tumor size were also associated with longer survival. Development of amenorrhea was associated with improved TTR and survival. Toxicity was similar for the two induction regimens and for the two maintenance regimens. Overall relapse patterns were similar among the induction regimens, but continuing Tam led to fewer locoregional relapses. CONCLUSION: The results suggest significant overall TTR therapeutic benefits of an Adriamycin-containing alternating induction regimen and of continuing maintenance Tam therapy for at least 5 years.

Adult↗
PubMed1992

HER-2/neu in node-negative breast cancer: prognostic significance of overexpression influenced by the presence of in situ carcinoma.

PURPOSE: Amplification and/or overexpression of the HER-2/neu oncogene have been shown to correlate with poor clinical outcome in patients with axillary node-positive breast cancer. In contrast, the prognostic significance of HER-2/neu in node-negative disease is controversial. This study was undertaken to evaluate further the relationship between HER-2/neu and clinical outcome in node-negative disease. PATIENTS AND METHODS: Overexpression of HER-2/neu was evaluated by permanent-section immunohistochemistry in tumors from 613 patients with long-term clinical follow-up enrolled in the Intergroup Study 0011. Patients were stratified into low-risk (n = 307) and high-risk (n = 306) groups on the basis of tumor size and estrogen-receptor (ER) status. Low-risk patients were defined as having small (less than 3 cm), ER-positive tumors and were observed without additional treatment after initial surgery. High-risk patients had either ER-negative or large (greater than or equal to 3 cm), ER-positive tumors and were randomized to be observed (n = 146) or to receive adjuvant chemotherapy (n = 160) after surgery. RESULTS: The rate of HER-2/neu overexpression was 14.3% in all tumors combined and was higher in invasive carcinomas with (21.5%) than without (11.2%) a significant noninvasive or in situ histologic component (P less than .0001). There was no relationship between overexpression and clinical outcome in the natural history setting of combined low-risk and high-risk patients not receiving adjuvant therapy (n = 453). Based on the reasoning that the influence of HER-2/neu may have been obscured by high-risk features and/or the presence of noninvasive carcinoma, we also analyzed the subset of patients with low-risk lesions not containing a significant in situ component (n = 179). Patients of this group with HER-2/neu-positive tumors showed only 40% disease-free survival (DFS) at 5 years, compared with over 80% in patients with HER-2/neu-negative tumors (P less than .0001). A similar inverse correlation was observed between overexpression and overall survival in the same group of patients (P = .0001). In a separate analysis involving patients receiving adjuvant chemotherapy, those with HER-2/neu-negative tumors showed significantly improved DFS in response to therapy compared with patients with HER-2/neu-positive tumors. CONCLUSION: Overexpression of HER-2/neu is associated with poor clinical outcome in a subset of node-negative patients with small, ER-positive, predominantly invasive tumors and may play a role in resistance to adjuvant chemotherapy.

Breast Neoplasms↗
PubMed1979

Malignant mesothelioma presenting in the pleura and peritoneum.

Malignant mesothelioma presenting in the pleura and peritoneum is described in a middle-aged man. The patient lacked significant asbestos exposure which is not unexpected from both the clinical literature and animal inhalation tumor data. Computerized axial tomographic correlation is provided. Partial remission was achieved with the administration of adriamycin and DTIC.

Adult↗
PubMed1979

Dibromodulcitol.

Explore the source record for details and available documents.

Animals↗
PubMed1979

Effects of steroid hormones on phytohemagglutinin-stimulated human peripheral blood lymphocytes.

The interactions of steroid hormones and human peripheral blood lymphocytes (PBLs) have been investigated following glass-wool column separation of PBLs and incubation in a serum-free medium in the presence of phytohemagglutinin (PHA). Addition of hydrocortisone or progesterone above physiological concentrations resulted in inhibition of [14C]2-TdR incorporation. 17beta-Estradiol and 5alpha-dihydrotestosterone inhibited [14C]2-TdR incorporation only at steroid concentrations thousands of times higher than the physiological concentrations. The kinetics of hydrocortisone and progesterone inhibition appeared to be similar and suggested that events occurring early after PHA addition were most sensitive to steroid inhibition and that addition of steroid at 28 hr, at the end of the early prereplicative phase of the cell cycle, inhibited DNA synthesis only at very high concentrations. The PHA-induced increase in RNA synthesis could be prevented by hydrocortisone addition even if delayed for up to 4 hr; morphological transformation was similarly affected. These data, and other investigations showing that progesterone binds to a specific glucocorticoid receptor in PBLs suggest that the progesterone inhibition of macromolecular synthesis in human PBLs is exerted via a glucocorticoid-like mechanism, and that glucocorticoid sensitivity is greatest during the early phases of lymphocyte activation. These results also provide a rationale for the apparent in vivo immunosuppressive capability of progesterone.

Cell Division↗
PubMed1978

Synovial sarcoma of the neck associated with previous head and neck radiation therapy.

Synovial sarcoma is a rare neoplasm that uncommonly arises in the neck. Fourteen years after facial and neck radiation therapy for acne, synovial sarcoma of the neck developed in a young man. Possible radiation-induced benign and malignant neoplasms that arise in the head and neck region, either of thyroid or extrathyroid origin, remain a continuing medical problem.

Acne Vulgaris↗
PubMed1978

The bone marrow examination in breast cancer: diagnostic considerations and clinical usefulness.

Bone marrow examinations were performed on 116 women with primary and metastatic breast cancer and were correlated with the clinical status of the patient and other specific diagnostic modalities. The relative diagnostic efficacy of the marrow biopsy, aspirate smear and clot section was examined, as was the value of serial marrow examinations. A marrow positive for tumor was found in 40% of those with metastatic disease, 55% with positive x-rays, 56% with positive bone scans, but only 4% (1/24) with both scan and x-ray normal. Routine hematologic parameters were of limited usefulness in predicting the finding of a positive marrow. The biopsy was superior to the smear and clot section but aspirated material also had to be analyzed to maximize diagnostic yield. When analyzed qualitatively, i.e., positive or negative for tumor, serial marrow examinations were not useful in assessing the efficacy of antitumor treatment. The potential usefulness of bone marrow examination in patients with breast cancer is discussed.

Biopsy, Needle↗
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↗