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Biomedical subjects

W B Farrar

Publications and source records attributed to W B Farrar.

At least 19 recordsLinked to original sources
PubMed1998

Stress and immune responses after surgical treatment for regional breast cancer.

BACKGROUND: Adults who undergo chronic stress, such as the diagnosis and surgical treatment of breast cancer, often experience adjustment difficulties and important biologic effects. This stress can affect the immune system, possibly reducing the ability of individuals with cancer to resist disease progression and metastatic spread. We examined whether stress influences cellular immune responses in patients following breast cancer diagnosis and surgery. METHODS: We studied 116 patients recently treated surgically for invasive breast cancer. Before beginning their adjuvant therapy, all subjects completed a validated questionnaire assessing the stress of being cancer patients. A 60-mL blood sample taken from each patient was subjected to a panel of natural killer (NK) cell and T-lymphocyte assays. We then developed multiple regression models to test the contribution of psychologic stress in predicting immune function. All regression equations controlled for variables that might exert short- or long-term effects on these responses, and we also ruled out other potentially confounding variables. RESULTS: We found, reproducibly between and within assays, the following: 1) Stress level significantly predicted lower NK cell lysis, 2) stress level significantly predicted diminished response of NK cells to recombinant interferon gamma, and 3) stress level significantly predicted decreased proliferative response of peripheral blood lymphocytes to plant lectins and to a monoclonal antibody directed against the T-cell receptor. CONCLUSIONS: The data show that the physiologic effects of stress inhibit cellular immune responses that are relevant to cancer prognosis, including NK cell toxicity and T-cell responses. Additional, longitudinal studies are needed to determine the duration of these effects, their health consequences, and their biologic and/or behavioral mechanisms.

Adult↗
PubMed1998

Biodistribution and localization of radiolabeled NR-LU-10 Fab fragment in human breast cancer xenografts.

Radioimmunodetection, which takes advantage of tumor-specific or tumor-associated radio-labeled monoclonal antibodies or other biologic molecules to diagnose the extent of disease in cancer patients, has been of limited use in studies to date in patients with breast cancer. The difficulty is in finding an antibody that is both sensitive and specific enough to localize in breast tumors. This study undertook immunohistochemical and in vivo evaluation of tumor localization and biodistribution of NR-LU-10 Fab (antibody fragment) in breast tumors to determine its ability to bind selectively to malignant tissue. NR-LU-10 Fab recognizes a pancarcinoma glycoprotein antigen found on tumors of epithelial cell origin. NR-LU-10 Fab reacted with 6/6 (100%) breast cancer cell lines and 14/16 (87.5%) breast tumors with varying degrees of immunostaining intensities. Athymic mice bearing ZR-75-1 breast cancer xenografts were injected with 125I-labeled NR-LU-10 Fab (12 microg/5 microCi) and sacrificed at fixed time intervals. These studies demonstrated the highest tumor uptake of labeled Fab at 12 h postinjection (4.58+/-1.59% of injected dose/gram [% ID/g] of tissue); this gradually decreased to 0.13+/-0.05% ID/g of tissue by 72 h postinjection of the radiolabeled Fab. Biolocalization to normal tissues was as predicted for a Fab fragment; i.e., initially high in clearance organs (kidney), followed by rapid clearance over the 72-h test period. NR-LU-10 Fab displays adequate breast tumor localization with minimal biolocalization to normal tissues, thus supporting its potential use in radioimmunoscintigraphy and the RIGS system (radioimmunoguided surgery).

Animals↗
PubMed1997

Seroma formation following axillary dissection for breast cancer: risk factors and lack of influence of bovine thrombin.

BACKGROUND: Seromas of the axillary space following breast surgery can lead to significant morbidity and delay in the initiation of adjuvant therapy. A prospective, randomized study was undertaken to evaluate the effect of bovine spray thrombin on seroma formation following either modified radical mastectomy (MRM) or lumpectomy with axillary dissection (LAD). In addition, risk factors for seroma formation were analyzed and identified. METHODS: A total of 101 patients were randomized to receive either bovine thrombin (20,000 units) (treatment group) or no thrombin (control group) applied to their axilla following either MRM or LAD. Drains were left in place until the preceding 24-hour drainage was < 40 milliliters. The number of days the drains were in place and wound complications (including seroma formation) were recorded. RESULTS: Forty-nine (n = 49) patients were assigned to the treatment gorup and 52 (n = 52) to the control group. MRM was performed on 60 patients (59%) and LAD oN 41 (41%). Eighteen of the 49 patients (37%) in the thrombin group developed a seroma in comparison to 21 of the 52 control patients (40%) (P = 0.71). Significant risk factors for seroma formation included increased age, patient weight, initial 72-hour wound drainage, and LAD. No statistically significant differences were observed between treatment and control groups with respect to time to drain removal, or the incidence of other wound complications. CONCLUSION: Although thrombin by itself appears to have no effect on subsequent seroma development following axillary dissection, the identification of predictive variables will be helpful in designing future trials aimed at reducing the incidence of this common complication of breast surgery.

Animals↗
PubMed1997

Androgens influence estrogen-induced responses in human breast carcinoma cells through cytochrome P450 aromatase.

The aromatase cytochrome P450 complex is responsible for the in vivo conversion of androgens to estrogens. Although breast cancer epithelial cells have been reported to have appreciable aromatase activity, its biologic significance remains uncertain. To address this, the effect of androgens on the expression of the estrogen-regulated gene pS2 in hormone-dependent human breast carcinoma cells in vitro was examined. Steroid-deprived MCF-7 cells were exposed to varying concentrations (1 nM, 10 nM, and 100 nM of androstenedione or testosterone for 2,4, and 6 days. Baseline aromatase activity was 4.9 (+/-3.1) fmol 3H2O/hour/microgram DNA [34.3 (+/-21.3) fmol/hr/10(6) cells] and was not influenced by the androgens. As an indication of estrogen biosynthesis, northern analysis was performed to quantitate pS2 mRNA expression. Although no significant pS2 induction was observed at 2 days, both 4 and 6 day exposure to 100 nM testosterone resulted in a 3-fold increase in pS2 mRNA expression. 5 alpha-dihydrotestosterone (5 alpha-DHT) failed to elicit a similar pS2 response. This testosterone-induced response was inhibited with the aromatase inhibitor 7 alpha (4'-amino) phenylthio-1,4-androstadiene-3,17-dione (7 alpha-APTADD) and with 10 microM tamoxifen. MCF-7 breast cancer cells possess endogenous aromatase activity at high enough levels to convert androgens to estrogens and elicit an estrogen-induced response. The expression of aromatase may offer a potential advantage to hormone-responsive cells, providing an additional autocrine growth pathway which may be exploited.

Androgens↗
PubMed1996

Nonsteroidal antiinflammatory drugs and breast cancer.

We examined the association of nonsteroidal antiinflammatory drugs and breast cancer risk in a case-control study of 511 breast cancer patients and 1,534 population control subjects. The relative risk of breast cancer was reduced in women using these compounds at least 3 times per week for > or = 1 year [odds ratio (OR) = 0.66; 95% confidence interval (CI) = 0.52-0.83]. Odds ratios were similar for use of ibuprofen (0.57) or aspirin per se (0.69). Breast cancer risk declined with increasing exposure, and the greatest risk reduction (40%; odds ratio = 0.60; 95% CI = 0.40-0.91) occurred at the highest level of use (daily intake for > or = 5 years). These results indicate that nonsteroidal antiinflammatory drugs may have chemopreventive potential against the development of breast cancer.

Adult↗
PubMed1996

Adjuvant CMFVP versus adjuvant CMFVP plus ovariectomy for premenopausal, node-positive, and estrogen receptor-positive breast cancer patients: a Southwest Oncology Group study.

PURPOSE: To determine whether the addition of surgical ovariectomy to standard chemotherapy prolongs disease-free survival (DFS) and overall survival in premenopausal patients with estrogen receptor (ER)-positive operable breast cancer with positive axillary nodes. PATIENTS AND METHODS: Three hundred fourteen premenopausal patients with ER-positive, node-positive breast cancer were enrolled between July 1979 and July 1989. Patients were stratified according to number of involved nodes and type of primary surgery and randomized to receive either of the following: (1) cyclophosphamide 60 mg/m2/d by mouth for 1 year, methotrexate 15 mg/m2 intravenously (i.v.) weekly for 1 year, fluorouracil (5-FU) 400 mg/m2 i.v. weekly for 1 year, vincristine .625 mg/m2 i.v. weekly for the first 10 weeks, and prednisone weeks 1 to 10 with doses decreasing from 30 mg/m2 to 2.5 mg/m2 (CMFVP); or (2) bilateral ovariectomy followed by CMFVP. RESULTS: The median follow-up time is 7.7 years and the maximum 13.2 years. Treatment arms are not significantly different with respect to either survival or DFS (one-sided log-rank, P = .55 and .70, respectively). The 7-year survival rate is 71% on the CMFVP arm and 73% on CMFVP plus ovariectomy. No significant differences were observed in node or receptor level subsets. CONCLUSION: We conclude that, in this study, the addition of ovariectomy did not improve results over chemotherapy alone in the treatment of premenopausal women with node-positive, ER-positive, operable breast cancer. Our sample size was too small to detect a small improvement. The death hazards ratio of CMFVP/CMFVP plus ovariectomy was 1.22 (95% confidence interval [CI], .79 to 1.89).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

The natural history of breast cancer with more than 10 positive nodes.

BACKGROUND: Experimental protocols are being used increasingly to treat breast cancer with > 10 positive nodes. An appreciation of the natural history of this disease is crucial for choosing the optimal therapeutic approach. PATIENTS AND METHODS: We retrospectively reviewed the records of 141 patients who had breast cancer with > 10 positive nodes and received definitive therapy at our institution in the years 1969 through 1991. Because therapy evolved during this period, we compared the results from 1969 through 1981 to those from 1982 through 1991. RESULTS: Ninety-one patients (65%) were > or = 50 years of age. Fifty-four (38%) were estrogen receptor (ER) positive, the remainder were ER negative or ER status unknown. Fifty-seven (40%) had 10 to 15 positive nodes, 63 (45%) had 16 to 25, and 21 (15%) had > 25. The ratio of positive nodes to total nodes was < 50% in 22 patients, 50% to 75% in 49, and > 75% in 70. One hundred thirty-four patients (95%) underwent modified or radical mastectomy. Forty (28%) received adjuvant chemotherapy, including 16 (11%) of 58 patients treated prior to 1981. Eleven patients (8%) were treated with adjuvant radiation therapy. The median survival for all patients was 52 months, with an actuarial survival of 29% at 10 years. Patients treated after 1981 had significantly improved survival. They lived a median of 68 months postoperatively, as compared to 41 months among patients treated earlier. CONCLUSIONS: This is a high-risk group of patients, yet there is a small subset who can obtain a long survival with standard treatment modalities.

Adult↗
PubMed1994

The regional treatment of liver metastases from breast cancer.

To determine the effect of aggressive regional therapy for liver metastasis from breast cancer, we retrospectively reviewed data on 74 patients identified with liver metastases. Forty had only liver metastases. In this group of 40 patients, 18 were treated with regional therapy only, i.e., surgical resection and/or regional chemotherapy via hepatic artery or portal vein catheters whereas 22 patients had systemic chemotherapy. The two groups were comparable. The regional chemotherapy regimen was 5-FU, Adriamycin, methotrexate, and cytoxan. Median survival (27 months) for those patients treated with regional therapy (N = 18) was significantly longer than for those (N = 22) treated with systemic therapy (5 months) (P = 0.001). Only 45% of the regional treatment group failed in the liver. Our data, although retrospective and selective, suggest that certain subgroups of breast cancer patients with metastatic liver disease may benefit from aggressive regional therapy.

Adult↗
PubMed1994

Adjuvant CMFVP versus tamoxifen versus concurrent CMFVP and tamoxifen for postmenopausal, node-positive, and estrogen receptor-positive breast cancer patients: a Southwest Oncology Group study.

PURPOSE: To compare chemohormonal therapy, chemotherapy alone, and hormonal therapy alone in postmenopausal patients with estrogen receptor (ER)-positive operable breast cancer and positive axillary nodes with respect to survival and disease-free survival (DFS). PATIENTS AND METHODS: Eight hundred ninety-two postmenopausal women with ER-positive, node-positive breast cancer were enrolled by the Southwest Oncology Group (SWOG) from July 1979 to March 1989 and 74 by the Eastern Cooperative Oncology Group (ECOG) between June 1987 and March 1989. Patients were stratified according to number of involved nodes and type of primary surgery and randomized to receive the following: (1) tamoxifen 10 mg twice daily by mouth for 1 year; (2) cyclophosphamide 60 mg/m2/d by mouth for 1 year, methotrexate 15 mg/m2 intravenously (IV) weekly for 1 year, fluorouracil (5-FU) 400 mg/m2 IV weekly for 1 year, vincristine .625 mg/m2 IV weekly for the first 10 weeks, and prednisone during weeks 1 to 10 with doses decreasing from 30 mg/m2 to 2.5 mg/m2 (CMFVP); or (3) the combination of tamoxifen and CMFVP. RESULTS: The median follow-up duration is 6.5 years, with a maximum of 12.8 years. Treatment arms are not significantly different with respect to either survival or DFS (log-rank, 2 df, P = .82 and .23, respectively). The 5-year survival rate is 77% for the tamoxifen arm, 78% for CMFVP, and 75% for the combination. No significant differences were observed in node or receptor level subsets. Severe or worse toxicity was experienced by 56% of patients on CMFVP and 61% on CMFVP plus tamoxifen, compared with 5% on tamoxifen alone. CONCLUSION: CMFVP chemotherapy, either alone or in combination with tamoxifen, has not been shown to be superior to tamoxifen alone in the treatment of postmenopausal women with node-positive, ER-positive, operable breast cancer.

Adult↗
PubMed1991

Clinical trials. Access and reimbursement.

Clinical trials continue to play an extremely important role in clinical oncology, but of the nearly 1 million cancer patients diagnosed in the United States each year, only 2.5% (25,000) participate in such trials. Access to clinical trials has been enhanced by the adoption by the NCI of a promotional campaign that involves seminars, dissemination of information to national and local news media, and assisting in making information about clinical trials available to patients and physicians. Factors that hinder accrual of patients to clinical trials include: (1) physicians' concern about losing contact with patients, (2) physicians who feel that "experimental therapy" is not as good as "standard therapy," and (3) the time it takes to discuss and implement clinical trials. Reimbursement for clinical trials has also become a major concern. Who should pay for clinical research? Many insurance companies have been reluctant to pay for "experimental therapy" but will pay for "standard therapy." If this trend continues, the whole concept and organization of clinical trials, i.e., Phase I, II, and III trials, will be greatly hindered. Solutions must be found, and third party payers need to realize that an investment in clinical trials today will decrease the long term costs of state-of-the-art care.

Clinical Trials as Topic↗
PubMed1990

Is DNA ploidy an independent prognostic indicator in infiltrative node-negative breast adenocarcinoma?

To evaluate DNA content as an independent, long-term prognostic indicator in infiltrative, node-negative adenocarcinoma of the breast, flow cytometric DNA analyses were performed retrospectively in 165 patients. The exclusive use of paraffin-embedded tissue permitted the study of patients for whom 3 to 15 years' follow-up was available. Other investigators have shown a relationship between DNA nuclear content and well-known prognostic indicators of breast carcinoma, such as estrogen receptors, age, menopausal status, and stage of tumor. However, very few of these studies were based on patients with long-term clinical follow-up and investigated the independent prognostic value of DNA nuclear content. The frequency of aneuploidy in the patients in this study was 57%, with DNA indices ranging from 0.73 to 2.59. Survival in patients with localized breast carcinoma with DNA aneuploid tumors was 84.1% at 5 years and 75.5% at 10 years. Those with diploid tumors showed survival of 87.8% at 5 years and 73.4% at 10 years. These data show no independent prognostic value for DNA nuclear content. The relationship between DNA content, tumor histologic type, and age was also investigated. High-grade tumors were more often aneuploid. There was no association between DNA content and age. Of 165 patients, information regarding estrogen receptor status was available in only 77; 45% of those with aneuploid tumors and 35% with diploid tumors were estrogen receptor-negative. This difference was not significant. The authors conclude that simple determination of DNA ploidy fails to indicate prognosis for infiltrative, node-negative breast carcinoma.

Adenocarcinoma↗
PubMed1990

Heterotopic pancreas.

Heterotopic pancreas will be encountered infrequently by the surgeon causing symptoms or incidentally at laparotomy. To avoid confusion with carcinoma at laparotomy, local excision with frozen section diagnosis is recommended. Because frozen section diagnosis will not always be correct, clinical awareness of this condition at operation is also important.

Adult↗
PubMed1990

Prospective evaluation of clinical and pathologic detection of axillary metastases in patients with carcinoma of the breast.

Complete axillary dissection was performed in 287 patients undergoing modified radical mastectomy between 1984 and 1987 to identify patterns of axillary node metastases, as well as discontinuous axillary node ("skip") metastases. Positive pathologic findings were compared with preoperative clinical examinations in 266 patients and showed only 60 cases (22.6%) clinically suspicious for tumor, in contrast to 131 (45.6%) with pathologically confirmed positive lymph nodes. Axillary contents were classified level I, II, or III based on their relationship to the pectoralis minor muscle. An average of 24.2 nodes was resected per patient (level I, 10; level II, 8.1; and level III, 5.3). Tumors ranged in size from 0.5 to 12.0 cm (mean, 2.6 cm), and increasing tumor size was associated with an increased likelihood of positive nodes. The data on 204 patients with complete clinical and pathologic data show that of 119 patients with negative level I nodes a limited axillary dissection (level I only) would fail to identify 6 with positive level II and 2 with positive level III nodes, whereas of 85 patients with positive level I nodes limited axillary dissection would fail to identify 17 with positive level II nodes, 7 with positive level III nodes, and 27 with positive levels II and III nodes. Complete axillary dissection (levels I, II, and III) should be performed to stage patients accurately, as well as to remove tumor-involved nodes and diminish local axillary recurrences. Clinical examination of the axilla appears to be a poor means of identifying axillary metastatic cancer.

Adult↗
PubMed1989

Follow-up on flow cytometric DNA analysis of squamous cell carcinoma of the tongue.

Preliminary data from this institution suggested that flow cytometric DNA analysis was an objective prognostic indicator in archival localized squamous cell carcinoma of the tongue. Technical improvements were made, including analysis of tumor, normal tissue, and a combination of the two; standardized cursor placement; mathematic determination of tetraploid populations; and development of a statistical analysis. A larger number of patients (60) with this disease were reviewed. DNA content was related to disease-free survival, local recurrence, regional metastasis, and incidence of second primary tumors. There was no significant difference between aneuploid and diploid tumors with respect to the variables analyzed. We believe these technical improvements will enhance flow cytometric DNA analysis of paraffin-embedded tissues. However, in this retrospective review of localized squamous cell carcinoma of the tongue, DNA analysis was not a valuable prognostic indicator. Only prospective studies will address this issue.

Adult↗
PubMed1989

Staging of carcinoma of the breast using a hand-held gamma detecting probe and monoclonal antibody B72.3.

Radioimmunoguided Surgery (RIGS) uses a hand-held gamma detecting probe to identify radiolabeled monoclonal antibodies (Mab). Fourteen patients with carcinoma of the breast proved at biopsy received Mab B72.3 (5 millicuries of 125I per 1 milligram, Iodo-Gen method) intravenously six to 26 days before exploration. Probe counts were measured intraoperatively in mammary tissue and axillary lymph nodes. In the mammary tissue, the RIGS system identified tumor that was histologically confirmed in seven of eight patients and confirmed the absence in four of six patients. Probe counts were suspicious for tumor that was not proved histologically in two of 14 patients. Unsuspected tumor was identified in three of 14 patients. In axillary tissue, probe counts identified one of two tumors that were confirmed histologically and verified the absence of tumor in eight of 12 patients. Probe counts in axillary tissue were suspicious for tumor that could not be documented histologically in four of 14 patients. RIGS appears to be able to identify residual, subclinical and multicentric carcinoma of the breast and accurately delineate the pattern of antigenic drainage of tumor into adjacent lymph nodes.

Antibodies, Monoclonal↗
PubMed1989

Radioimmunoguided surgery in recurrent colorectal cancer: the role of carcinoembryonic antigen, computerized tomography, and physical examination.

From January 1986 to December 1987, 32 patients with recurrent colorectal cancer had second-look radioimmunoguided surgery (RIGS system). All patients had pathologic confirmation of recurrence. The RIGS system identified 81% of recurrences, and in six patients recurrent tumor was identified only by RIGS. All patients had physical examination, carcinoembryonic antigen (CEA) assay, and computerized tomography of the abdomen and pelvis. Detection of recurrence was based on symptoms in six, elevated CEA value in 25, and physical examination in one. The CEA was elevated preoperatively in 30 patients; two false-negative results occurred in symptomatic patients who had pelvic recurrence. The median CEA value in those with liver recurrence was 30 ng/ml (range 5.2 to 298) and for pelvic recurrence 13 ng/ml (range 1.9 to 31) (P less than .05). The overall sensitivity of CT was 41% (abdomen other than liver 37%, liver 56%, and pelvis 22%). The combination of elevated CEA, symptoms, and physical findings identified 100% of recurrences. We conclude that a rising CEA remains the most accurate indicator of recurrence. CT should not be done routinely to detect recurrent colorectal cancer unless CEA is elevated or the patient is symptomatic. In our study the intraoperative use of the RIGS system aided the surgeon in identifying occult tumors.

Adolescent↗
PubMed1988

Technical and statistical improvements for flow cytometric DNA analysis of paraffin-embedded tissue.

Flow cytometric DNA analysis of paraffin-embedded solid tumors has permitted review of large series of archival tissue in attempts to relate abnormal DNA content to prognosis. Limitations of the technique include: 1) a laborious, time-consuming procedure; 2) variation in technique between laboratories; and 3) lack of an objective method of computing DNA indices. Critical evaluation of our technique has shortened the time involved in dewaxing and rehydration, selectively utilized patient's own normal tissue as the internal standard, proved reproducibility of stored specimens, standardized DNA index computation, and developed a statistical analysis to confirm aneuploidy. These technical improvements and the development of a statistical analysis provide a way to shorten the procedure time and standardize the data generated from flow cytometric DNA analysis so as to improve the quality of retrospective reviews of paraffin-embedded tumors and accelerate the definition of flow cytometry's role as a prognostic indicator.

Breast Neoplasms↗