Search PubMed⌕ Search

Biomedical subjects

L Norton

Publications and source records attributed to L Norton.

At least 109 records · Page 6Linked to original sources
PubMed1996

Sequential adjuvant therapy: the Memorial Sloan-Kettering Cancer Center experience.

Adjuvant chemotherapy has a real but modest impact on the disease-free and overall survival of patients with breast cancer. Recent attempts to improve its effectiveness have focused on dose intensity and new agents. Sequential therapy maximized dose intensity while limiting overlapping toxicity. Sequential therapy using doxorubicin followed by cyclophosphamide/methotrexate/5-fluorouracil (CMF) has been found superior in patients with high-risk resectable breast cancer. The novel chemotherapy agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is now known to be highly active in advanced breast cancer and appears to be clinically non-cross-resistant with doxorubicin. Therefore, this drug is being studied as a component of the next generation of adjuvant chemotherapy regimens. The most appropriate way to incorporate paclitaxel has not yet been defined, but its concurrent administration with other agents has, in some cases, been troublesome. Based on the demonstrated advantage of the sequential plan for doxorubicin and CMF, we conducted a series of pilot trials testing sequential high-dose therapy. Initially, we studied multiple cycles of doxorubicin followed by cyclophosphamide; we later added paclitaxel to this regimen. These phase II studies demonstrate the feasibility of sequential therapy with doxorubicin, paclitaxel, and cyclophosphamide, and early disease-free survival results are promising. Cooperative group projects are under way or planned to further define the activity of these regimens.

Antineoplastic Agents, Phytogenic↗
PubMed1996

Adjuvant drug therapy for operable breast cancer.

Breast cancer-the most common malignancy of lethal potential for women in the developed world-presents as two interrelated problems: (1) local disease in the breast and axillary lymph nodes, and (2) micrometastatic disease in distant sites. During the last century, advances in surgery and radiotherapy have led to high rates of control over local disease. In addition, heightened public awareness and the more widespread use of mammography have led to the more frequent detection of smaller cancers with better prognosis. Nevertheless, the problem of distant recurrence, leading almost inevitably to death, persists. Hence, there is considerable interest in integrating systemic therapy, which since mid-century has been shown to be active against advanced disease, into the treatment of primary breast cancer. The long-standing theoretical prediction of benefit from drug therapy as an adjunct to local control procedures has now been confirmed by several decades of clinical investigation. Long-term follow-up of seminal trials and the conduct of a crucial series of meta-analyses have established the ability of both hormonal therapies and chemotherapy to prolong disease-free and overall survival in nearly all groups of patients. Although the relative and absolute influences of drug therapies remain modest, if these were properly applied to the hundreds of thousands of patients diagnosed worldwide per year, the potential impact on public health would be significant. In addition, recent laboratory advances and clinical trial data have indicated several new directions that promise greater impact against occult disseminated disease. These include novel dosing and scheduling strategies, newer active agents, fresh biochemical targets, and different combinations of chemotherapy with hormonal therapy.

Age Distribution↗
PubMed1995

A phase II trial of extracorporeal plasma immunoadsorption of patient plasma with PROSORBA columns for treating metastatic breast cancer.

BACKGROUND: Circulating immune complexes (CIC) have been implicated as a cause of malignancy-associated immunosuppression and disease progression. Previous attempts to remove CIC by pheresis or immunoadsorption over a Staphylococcus aureus protein A column have resulted in a few clinical responses, however the relationship between removal of CIC and tumor response in these trials is not clear. Based on these data, a Phase II trial of immunoadsorption over a Staphylococcus aureus protein A column was initiated for patients with metastatic breast cancer. The authors sought to correlate clinical response with amount of CIC eluted from the columns after immunoadsorption. METHODS: The potential role of extracorporeal immunoadsorption was determined using protein A columns in treating patients with advanced breast cancer. An immunoadsorbent column composed of protein A was bound covalently to an inert silica matrix (PROSORBA [IMRE Corporation, Seattle, WA] column). Patients underwent a 3-hour on-line procedure phlebotomizing 2000 ml of whole blood. Patient plasma was passed over PROSORBA columns to remove immunoglobulin G (IgG) and IgG-related CIC. The treated plasma then was reunited with formed elements and reinfused into the patient. Patients were treated three times per week for a total of 4 weeks. Analyses of tumor-associated Le(x)-containing CIC adsorbed on PROSORBA columns were performed using an enzyme-linked immunosorbent assay technique with a monoclonal antibody specific for the Le(x) moiety. RESULTS: Sixteen patients were entered in this Phase II study, with a mean age of 57 years (range, 40-69 years). All patients received prior treatment for Stage IV breast cancer. The median number of PROSORBA treatments was 12 (range, 1-15 treatments). No toxicities or major objective responses were seen noted the 16 patients. One patient with severe chest wall pain had a symptomatic response. The remaining patients all had disease progression. Analyses of column eluates from 11 patients in this study revealed no detectable Le(x)-containing immune complexes when compared with control subjects. CONCLUSIONS: Immunoadsorption over a Staphylococcus aureus Protein A column had no meaningful antitumor activity in patients with advanced breast cancer. In this cohort of patients, an elevated level of Le(x) CIC was not confirmed in the eluates of the column compared with a control group of patients without cancer.

Adult↗
PubMed1995

Immunohistochemical detection of HER2/neu in patients with axillary lymph node negative breast carcinoma. A study of epidemiologic risk factors, histologic features, and prognosis.

BACKGROUND: Numerous studies have examined the prognostic significance of HER2/neu (HER) expression in patients with axillary lymph node negative breast carcinoma. Although some investigations suggest that the presence of the altered expression of HER is prognostically unfavorable, the subject remains controversial. This study explores the interaction of HER with three aspects of axillary lymph node negative breast carcinoma: epidemiologic risk factors, tumor histopathology, and prognosis. METHODS: Immunohistochemical staining for HER was performed on 10% formalin fixed paraffin embedded primary carcinomas from 440 patients with negative axillary lymph nodes with a median follow-up of 119 months. RESULTS: The immunohistochemical expression, or lack thereof, of HER did not prove to be prognostically significant in this group of patients with axillary lymph node negative breast carcinoma. There was also no consistent association with epidemiologic risk factors. The most striking results concerned the relationship of HER to histopathologic features of the carcinomas. Medullary carcinoma differed from other tumor types because it was HER(+) substantially less often (10%) than were other ductal (49%) or lobular (43%) carcinomas. CONCLUSION: The results obtained in this study suggest that the immunohistochemical demonstration of HER is not a reliable prognostic indicator for patients with axillary lymph node negative breast carcinoma. This marker was not associated with major epidemiologic risk factors; however, there was a significant correlation between HER and the phenotypic features of breast carcinoma because medullary carcinoma is rarely HER(+). Although the associations may not be a strong enough basis for refining the classification of breast carcinoma, they could be useful for diagnosing individual patients. The changes in HER that are detectable by the immunohistochemical methods used in this study probably do not occur in the earliest stages of mammary carcinogenesis.

Breast Neoplasms↗
PubMed1995

The effect of electrical perturbation on osseointegration of titanium dental implants: a preliminary study.

PURPOSE: Successful osseointegration of titanium dental implants is decreased in areas of poor bone volume and density. Low amperage direct current (LADC) has been shown to perturb bone cells, which in turn promotes bone growth. The purpose of this experiment was to evaluate the effect of LADC on the osseointegration of endosseous titanium dental implants. MATERIALS AND METHODS: Two implant sites were prepared in the body of the mandible of five rabbits by an extraoral approach. An LADC-stimulated 3.75 x 7 mm-titanium implant was placed in one site and an identical control implant was inserted on the contralateral side. A sterilized silicone-encased power pack producing 7.5 +/- 0.2 uA and 1.35 +/- 0.01 V was placed in a submandibular pouch. The active cathode lead was attached to the LADC implant and the anode was placed in the mandible 5 mm distal to the implant. Nonactive leads were similarly connected to the control implant. Twenty-eight days after placement, the implants were removed using a torque wrench, and the bone surrounding the implants was examined both microscopically and radiographically. RESULTS: The average force to initial rotation was 1,320 +/- 880 g/cm for the LADC-stimulated implants and 1,290 +/- 238 g/cm for the control implants. This was significantly different by t test (P = .94). Light microscopic evaluation demonstrated a mixture of compact and woven bone and fibrous tissue adjacent to both groups of implants. Histomorphometric analysis demonstrated an average percent of bone in relation to the total tissue adjacent to the control implants of 33.5 +/- 15.4 and 40.2 +/- 4.8 for the LADC-stimulated implants (not significantly different, t test, P = .39). CONCLUSION. It was concluded that LADC as used in this study does not positively affect the healing of bone. Its ability to enhance bone growth around titanium dental implants needs further investigation.

Animals↗
PubMed1995

Conditioned emotional distress in women receiving chemotherapy for breast cancer.

This study investigated whether women undergoing outpatient chemotherapy for breast cancer can develop classically conditioned emotional distress. Women scheduled to begin chemotherapy were randomly assigned either to an experimental group (exposed to a distinctive stimulus before each chemotherapy infusion) or a control group. After repeated infusions of chemotherapy, patients' responses to the distinctive stimulus were assessed in a location not associated with chemotherapy administration. At the test trial, experimental group patients showed evidence of increased emotional distress (self-reported on a visual analog scale) after the presentation of the distinctive stimulus, whereas control group patients did not. Post hoc analyses indicated that these increases in distress were not secondary to other conditioned responses (e.g., nausea, taste aversion). Thus, results supported the hypothesis that the pairing of a distinctive stimulus with chemotherapy would result in the development of a conditioned emotional response.

Adolescent↗
PubMed1995

Potential strategies for improving the results of high-dose chemotherapy in patients with metastatic breast cancer.

High-dose chemotherapy (HDC) is the most effective approach for inducing complete remissions in patients with metastatic breast cancer, and although most patients will relapse, a small percentage (10%-15%) achieve durable remissions beyond five years. Additionally, HDC has produced five-year relapse-free survival rates in excess of 70% in patients with stage II breast cancer with > 10 nodes. The use of HDC in breast cancer remains controversial and randomised trials are required to assess the survival impact of this approach. The introduction of haematopoietic growth factors (HGF) and peripheral blood progenitor cells (PBPC) has advanced the use of HDC by reducing treatment-related mortality (from 20% to 5%) and by allowing the development of multiple cycles of intensive therapy. Based on tumour kinetic models we have hypothesised that multiple, rapidly cycled courses of high-dose therapy may improve the rate of durable remission in metastatic breast cancer. The feasibility of this approach has been shown in a series of pilot studies in which one or more courses of high-dose cyclophosphamide and recombinant granulocyte colony-stimulating factor (G-CSF) (filgrastim) were given to obtain PBPC which were then used to support one or more courses of HDC. In successive studies the HDC component consisted of: a single course of carboplatin, etoposide and cyclophosphamide; four courses of carboplatin; tandem courses of thiotepa; or a sequence of melphalan and thiotepa. Promising response rates have been produced in advanced breast and ovarian cancer with the later generation of regiments. These results justify the conduct of prospective randomised trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Sources of anticipatory emotional distress in women receiving chemotherapy for breast cancer.

BACKGROUND: The contribution of classical conditioning processes to patients' distress before chemotherapy infusions (anticipatory distress) was compared to other potential sources of distress (e.g., trait anxiety). We hypothesized that posttreatment distress (putative unconditioned response) would become a stronger predictor of anticipatory distress as patients underwent more treatment infusions (putative conditioning trials). MATERIALS AND METHODS: Fifty women with early stage breast cancer, undergoing standard chemotherapy, completed questionnaires in the clinic prior to each of eight consecutive treatment infusions, as well as telephone interviews to assess side effects following infusions. RESULTS: Consistent with the conditioning hypothesis, posttreatment distress became significantly related to anticipatory distress at the fourth infusion and became the strongest predictor by the sixth. Path analysis indicated that posttreatment distress had a direct influence on anticipatory distress, and that trait anxiety had an indirect influence by influencing apprehension about chemotherapy which, in turn, directly predicted anticipatory distress. CONCLUSIONS: The results of the present study contribute to an emerging view of anticipatory distress as a conditioned response in chemotherapy patients. Results demonstrate that conditioning factors may be one of the strongest predictors of anticipatory distress in the later phases of chemotherapy treatment.

Adult↗
PubMed1995

Microdissection and molecular genetic analysis of HER2/neu in breast carcinoma.

Precise correlation of histomorphology with molecular genetic analysis is difficult in tissues composed of heterogeneous cell populations. We describe here a novel microdissection technique employed to correlate HER2/neu (HER2) immunohistochemical staining with HER2 genetic analysis in formalin-fixed, paraffin-embedded breast tissue. Fourteen invasive ductal carcinomas were selected from the pathology files of Memorial Sloan-Kettering Cancer Center that had been immunostained for HER2. Seven tumors showed typical membrane immunoreactivity and seven were negative. A dissecting microscope was then used to isolate minute (< or = 1 mm x 1 mm) areas of invasive carcinoma and normal breast tissue for molecular study. To document the type of cell sample submitted for polymerase chain reaction (PCR) analysis, each microdissected piece of tissue was photographed prior to removal from the glass slide. A preliminary study of four cases compared the results of PCR and genetic analysis using microdissected hematoxylin and eosin (H & E)-stained tissue, unstained dewaxed tissue, and destained dewaxed tissue in four specimens. Similar results were obtained with all three tissue preparations. Thereafter, H & E stained sections were selected as the tissue preparation of choice because tissue details were seen more clearly. There was complete correlation of immunohistochemical staining and HER2 analysis by PCR in all 14 cases. In the final 10 cases, the PCR product was resolved by gel electrophoresis and quantified by optical densitometry. Fourfold to eightfold amplification of HER2 was found in the five tumor specimens that immunohistochemically stained for HER2. A single copy of HER2 was found in all HER2-negative tumors and in normal breast tissue. We conclude that it is possible to quantify gene amplification of HER2 in minute samples of H & E-stained normal and malignant breast tissue. This microdissection technique can be applied to correlative histologic--molecular genetic analysis in a wide variety of tumor types.

Breast Neoplasms↗
PubMed1995

Complementary therapies in practice: the ethical issues.

This article explores some of the ethical issues associated with the use of complementary therapies in practice. The adopted terminology and related concepts are clarified. The term 'complementary therapy' is compared and contrasted with 'alternative medicine' and 'non-conventional therapy'. The increasing emphasis on holistic nursing care is also discussed. Ethical issues of patient choice, informed consent and the principle of beneficence are examined in relation to complementary therapies. The article highlights the obligation of the nurse, midwife or health visitor to provide or facilitate holistic care including complementary therapies, such as massage or aromatherapy, for those clients who request such care, and where it can be demonstrated that there will be benefits for the patient. It is concluded that nurses should consider the possibility of incorporating or facilitating certain complementary therapies in their practice in order to benefit their patients. There is a corresponding need for an appropriate knowledge base, founded on nursing research, into the effectiveness and outcomes of complementary therapies. In addition, relevant educational courses should be developed.

Complementary Therapies↗
PubMed1995

Are axillary recurrence and overall survival affected by axillary extranodal tumor extension in breast cancer? Implications for radiation therapy.

PURPOSE: To determine the overall survival and local recurrence significance of axillary lymph node extranodal tumor extension (ETE) and whether axillary/chest-wall irradiation influenced any of these outcomes. MATERIALS AND METHODS: The records of 81 breast cancer patients treated with radical or modified radical mastectomy at a single surgical practice were eligible for study. Thirty-four patients had ETE: 17 with focal ETE (< 10 x high-power field) and 17 with extensive ETE (> 10 x high-power field). RESULTS: With a median follow-up duration of 92 months, only two patients had an axillary recurrence (2%): one had focal ETE and one had no ETE. Neither of these patients received axillary radiation therapy. Overall survival and recurrence-free survival were significantly decreased with ETE in patients whether axillary radiation therapy had been administered or not. Analysis showed that the age of the patient correlated significantly with extensive ETE (P = .04) and that the number of positive lymph nodes (< or = three v > three) correlated significantly with ETE (whether focal or extensive) (P = .0001). A multivariate analysis of extranodal tumor extension and number of positive lymph nodes showed that ETE was associated with decreased survival (P = .05), although to a lesser degree than number of positive lymph nodes (P = .003). CONCLUSION: These results show that ETE is associated with decreased survival and increased recurrence rates regardless of the extent of the radiation therapy field. Also, ETE does not necessarily indicate a significantly increased incidence of axillary recurrence. Therefore, axillary irradiation based on this pathologic finding may not be indicated.

Age Factors↗
PubMed1995

Does administration of chemotherapy before radiotherapy in breast cancer patients treated with conservative surgery negatively impact local control?

PURPOSE: To determine if a delay of irradiation to the intact breast for administration of adjuvant chemotherapy results in increased local recurrence in breast cancer. PATIENTS AND METHODS: The records of 262 women with 264 cases of breast cancer were reviewed. Group I contained 105 patients treated with conservative surgery, chemotherapy, and radiotherapy. Group II contained 157 patients (used as a concurrent control) treated with conservative surgery and radiotherapy only. Eighty-nine percent of subjects in group I received all chemotherapy before radiotherapy. Fifty-eight percent of patients received hormone therapy. Seventy-one percent of patients had negative surgical margins, and 74% had negative lymph nodes. For group I, conservative surgery-radiotherapy intervals in months were less than 1 (five, 5%), > or = 1 to less than 3 (10, 9%), > or = 1 to less 6 (48, 46%), and > or = 6 (42, 40%), mean of 5. For group II, the intervals were less than 1 (20, 13%), > or = 1 to less than 3 (123, 79%), > or = 3 to less than 6 (11, 7%), and > or = 6 (two, 1%), mean of 1.5. RESULTS: Thirty patients (11.5%) have disease recurrence (19 distant [6%] and 12 local [5%]). There were no significant differences in local recurrence (group I, four [4%]; group II, eight [5%]; difference not significant). There were no significant differences in local recurrence in any surgery-radiotherapy interval within each group. Although we found marginal increases in the percentage of local recurrences in group I patients (with prolonged surgery-radiotherapy intervals) who had positive margins, positive lymph nodes, and tumor size more than 2 cm versus group II (without prolonged surgery-radiotherapy intervals), these results were not significant. CONCLUSION: We could not identify any surgery-radiotherapy interval that resulted in increased local recurrence if radiotherapy was delayed for administration of adjuvant chemotherapy in breast cancer patients. Because of the heterogenous population of breast cancer patients, our results also support the need for further study to determine the optimum integration of radiotherapy and chemotherapy in the management of the conservatively treated breast.

Adult↗
PubMed1995

p53 in node-negative breast carcinoma: an immunohistochemical study of epidemiologic risk factors, histologic features, and prognosis.

PURPOSE: The present study explores p53 in relation to the following four aspects of node-negative breast carcinoma: epidemiologic risk factors, tumor histopathology, prognosis, and HER2/neu (HER) expression. MATERIALS AND METHODS: Immunohistochemical (IH) staining for p53 was performed on formaldehyde-fixed, paraffin-embedded primary invasive carcinomas from 440 node-negative patients with a median follow-up duration of 119 months. RESULTS: The IH expression, or lack thereof, of p53 separately or in combination with HER did not prove to be prognostically significant and there was no consistent association of p53 with epidemiologic risk factors. p53 was expressed in 68% of medullary carcinomas (MEDs), which is a significantly higher frequency (P < .001) than in lobular (9%) and duct (23%) carcinomas. p53 was not found in some types of low-grade carcinomas (tubular and papillary), and was observed in a minority of mucinous carcinomas. p53 was present significantly more often in carcinomas with high-grade or poorly differentiated nuclear grade than in low- or intermediate-grade tumors. There was an inverse statistically significant relationship between estrogen receptor (ER) positivity and p53 expression. Tumors with the p53(+)/HER(-) immunophenotype tended to be MEDs or duct carcinomas with a marked lymphoplasmacytic reaction. Infiltrating lobular carcinomas (IFLCs) were largely p53(-)/HER(-). p53(+)/HER(+) carcinomas had the best prognosis. The poorest outcome was associated with the p53(-)/HER(+) immunophenotype. This trend was statistically significant for recurrence-free and overall survival in patients with T1NOMO infiltrating duct carcinoma (IFDC). CONCLUSION: The IH demonstration of p53 was not a reliable prognostic indicator in the node-negative breast carcinoma patients studied and it was not associated with major epidemiologic risk factors. The combined immunophenotypic expression of p53 and HER was significantly associated with some histologic types of breast carcinoma and with prognosis in T1NOMO breast carcinoma.

Breast Neoplasms↗