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Biomedical subjects

P D Hall

Publications and source records attributed to P D Hall.

At least 19 recordsLinked to original sources
PubMed2001

Antibody response to DT-GM, a novel fusion toxin consisting of a truncated diphtheria toxin (DT) linked to human granulocyte-macrophage colony stimulating factor (GM), during a phase I trial of patients with relapsed or refractory acute myeloid leukemia.

We are conducting a Phase I trial of a fusion toxin (DT-GM) for the treatment of relapsed or refractory acute myeloid leukemia (AML). The fusion toxin consists of a truncated diphtheria toxin (DT) linked to human granulocyte-macrophage colony stimulating factor (GM). Prior to beginning the Phase I trial, our first goal was to determine whether healthy controls and adult AML patients had preexisting antibodies able to inhibit DT-GM. Sera from 5 of the 9 controls completely neutralized DT-GM by an in vitro bioassay to assess the inhibition of DT-GM. Sera from 43 patients with AML were tested by bioassay and a specific enzymoimmunoassay (EIA) for anti-DT-GM antibodies. Forty-two of 43 samples were positive by EIA, and 5 patients (11.6%) showed complete neutralization of DT-GM in the bioassay. Anti-DT-GM concentrations were significantly higher in samples demonstrating neutralization than in samples demonstrating no neutralization (P = 0.003). In the Phase I trial of DT-GM prior to therapy, none of 28 patients exhibited neutralization by bioassay, but 89% were positive by EIA. After the first course of DT-GM, 23% developed neutralizing antibodies by the bioassay, and 64% of patients exhibited an increase in their anti-DT-GM antibody concentrations by EIA. Further studies are needed to determine the clinical impact of the anti-DT-GM antibodies and whether the neutralization bioassay can be replaced by our EIA.

Adult↗
PubMed2001

Focal nodular hyperplasia with calcification and ossification.

We describe a 33-year-old woman with Crohn's disease, who presented with recurrent episodes of small bowel obstruction. A solitary liver lesion was discovered incidentally by abdominal ultrasound. Pathological examination of the resected specimen revealed features typical of focal nodular hyperplasia together with uncommon findings including calcification, ossification and fibrous obliteration of blood-filled "cysts", changes more commonly associated with regression in hepatic haemangiomas. This report strengthens the favoured hypothesis that a vascular malformation underlies the pathogenesis of focal nodular hyperplasia.

Adult↗
PubMed2000

Electrolytic treatment of colorectal liver tumour deposits in a rat model: a technique with potential for patients with unresectable liver tumours.

BACKGROUND/AIMS: Patients with unresectable malignant liver tumours have a poor prognosis. A technique is needed which improves long-term survival. Previous studies in the rat have shown that electrolysis is a safe, predictable and reproducible method for creating areas of necrosis in the normal rat liver. This study examined the effects of electrolysis on colorectal liver 'metastases' in the rat. METHODS: Tumours of colorectal origin were implanted into the livers of Wistar-WAG rats. Two weeks after implantation the tumours were treated with electrolysis. A direct current generator, connected to 2 platinum intrahepatic electrodes was used to examine the effects of various electrode configurations on the extent of tumour necrosis. RESULTS: Significant (p<0.001) tumour ablation was achieved with all electrode configurations. Tumour necrosis was more complete (p<0.05) with the electrodes positioned on either side of the tumour than with both electrodes placed in the centre of the tumour. Liver enzymes (AST and ALT) were significantly (p<0.001) elevated after treatment, but returned towards normal by 2 days. CONCLUSIONS: This study has shown that colorectal liver 'metastasis' can be ablated by electrolysis in a rat model. Two separate mechanisms of tumour ablation were observed: With the electrodes directly in or adjacent to the tumour, necrosis resulted from the action of cytotoxic electrode products, whereas by positioning the electrodes proximal to the tumour, necrosis was induced by a 'secondary' ischaemic effect. The findings confirm the view that electrolysis has great potential for treating patients with unresectable malignant liver tumours.

Adenocarcinoma↗
PubMed2000

Development of CPR security using impact analysis.

The HIPAA regulations will require that institutions ensure the prevention of unauthorized access to electronically stored or transmitted patient records. This paper discusses a process for analyzing the impact of security mechanisms on users of computerized patient records through "behind the scenes" electronic access audits. In this way, those impacts can be assessed and refined to an acceptable standard prior to implementation. Through an iterative process of design and evaluation, we develop security algorithms that will protect electronic health information from improper access, alteration or loss, while minimally affecting the flow of work of the user population as a whole.

Algorithms↗
PubMed2000

Influence of intestinal flora on the development of fibrosis and cirrhosis in a rat model.

BACKGROUND AND AIMS: The gut flora play a significant role in the disposition of many foreign substances, as well as producing nutrients and toxins that may be absorbed and reach the liver. This study examines the influence of antibiotic-induced alterations in gut flora on the development of hepatic fibrosis in a rat model. METHODS: Thirty-six male Porton rats were fed alcohol (3.9 g/kg per day) in the drinking water and exposed to carbon tetrachloride (CCl4) vapor (80 p.p.m.) for 6 h each night, five nights per week. Half were also given neomycin (330 mg/kg per day) and polymyxin B (105 mg/kg per day) in the drinking water. Fecal cultures were carried out at 0, 3, 8 and 13 weeks; rats were killed at 14 weeks. Coded liver section were assessed for fibrosis using a graded scale (0, no abnormal fibrosis to 4, early or established cirrhosis). RESULTS: Rats that received antibiotics had significantly higher fibrosis scores than those that did not (mean score 2.4 vs 1.4, P < 0.01, ordinal logistic regression). Three rats, all of which were in the antibiotic group, were cirrhotic. Rats that had received antibiotics fell into three groups. Four had overgrowth of Proteus mirabilis; in these the fibrosis scores (mean 1.5) were similar to those in the rats that did not receive antibiotic. In six, no organisms could be cultured; fibrosis scores of these (mean 2.3) were slightly elevated (P = 0.03), but this was mainly because of a single rat in this subgroup being cirrhotic. The remaining eight had overgrowth of Morganella morganii; these had significantly (P < 0.001) elevated fibrosis scores. Furthermore, in this subgroup, fibrosis scores were significantly correlated (Spearman's r = 0.82, P = 0.01) with the number of weeks of Morganella colonization. CONCLUSIONS: Antibiotic treatment exacerbated fibrosis in the alcohol/CCl4 rat model; this effect appeared to be related to the type of gut flora and may be endotoxin-mediated.

Animals↗
PubMed1999

Toxicology and pharmacokinetics of DTGM, a fusion toxin consisting of a truncated diphtheria toxin (DT388) linked to human granulocyte-macrophage colony-stimulating factor, in cynomolgus monkeys.

We developed a fusion toxin consisting of the catalytic and translocation domains of diphtheria toxin linked to human granulocyte-macrophage colony-stimulating factor (GM-CSF) (DTGM) for the treatment of patients with acute myeloid leukemia (AML). Our goal in this study was to determine the toxicity and pharmacokinetics of DTGM in cynomolgus monkeys (Macacca fascicularis), which possess cross-reactive GM-CSF receptors. Four groups of young adult monkeys (6 males and 12 females) were treated with five daily bolus iv infusions of 1, 5, 7.5, and 10 microgram/kg DTGM. Monkeys (2 males and 2 females) treated at 1 microgram/kg/day showed no significant side effects. Monkeys (2 males and 2 females) treated at 5 microgram/kg/day showed Grade 1-2 thrombopenia (NCI common toxicity criteria) on day 9. In contrast, monkeys (6 females) treated at 7.5 microgram/kg/day developed Grade 3 neutropenia, Grade 1-2 thrombopenia, Grade 1-3 anemia, and Grade 1-3 hypoalbuminemia. The neutropenia developed by day 4 in the 7.5 microgram/kg/day monkeys and by day 3 or 5 in the 10 microgram/kg/day monkeys and resolved in both groups by day 9, but the thrombopenia, anemia, and hypoalbuminemia persisted until day 16. Monkeys (2 male and 2 female) treated with 10 microgram/kg/day showed Grade 4 neutropenia that resolved by day 8 and Grade 2-3 anemia, hypoalbuminemia, and thrombopenia. Three of the animals developed sepsis. DTGM plasma half-life was 30 min with a peak concentration of 0.1 microgram/mL or 2 nM (1000-fold higher than the IC50 in vitro for AML blasts). Immune responses were minimal in all animals tested at 14 and 28 days with anti-DTGM levels <1 microgram/mL. All four animals at 10 microgram/kg died or were euthanized, and necropsies were performed. Animals necropsied on days 4 and 6 showed marked apoptosis and hypoplasia in the marrow, which was completely resolved for animals necropsied on day 9. No injury to other organs, including kidney, heart, liver, central nervous system, or lung, was seen. The drug was selectively toxic to malignant or differentiated myeloid cells with little toxicity to myeloid progenitors or other organs. Minimal effects in nontarget tissues make DTGM a promising candidate chemotherapeutic agent.

Animals↗
PubMed1999

DT388-GM-CSF, a novel fusion toxin consisting of a truncated diphtheria toxin fused to human granulocyte-macrophage colony-stimulating factor, prolongs host survival in a SCID mouse model of acute myeloid leukemia.

Despite significant advances in the treatment of acute myeloid leukemia (AML), the majority of patients will succumb to drug-resistant AML. To overcome this resistance, we have developed a novel fusion toxin consisting of the catalytic and translocation subunits of diphtheria toxin (DT388) linked to human granulocyte-macrophage colony-stimulating factor (GM-CSF). In vitro, DT388-GM-CSF demonstrated significant activity against numerous AML cell lines and fresh AML blasts. To determine its in vivo efficacy, we developed an in vivo model of human AML in severe combined immunodeficiency (SCID) mice injected intravenously with 1 x 10(7) HL-60 cells (AML-M2 cell line). The SCID mice developed abdominal masses, infiltration of the liver and bone marrow, and peripheral blasts with a median survival of 42.5 days. We tested DT388-GM-CSF, ara-C, human GM-CSF, and DAB389IL-2, which were injected intraperitoneally on days 2-6 in this model. DT3-GM-CSF significantly improved survival of the SCID mice over Ara-C, DAB389IL-2, or control (P < 0.001). DT388-GM-CSF-treated mice who developed leukemia exhibited no difference in the number of GM-CSF receptors (P = 0.39), ligand affinity (P = 0.77), or sensitivity (P = 0.56) to DT388-GM-CSF as compared to the controls. Frank leukemia in DT388-GM-CSF-treated mice may be due to incomplete penetration of drug into tissues rather than cellular resistance. DT388-GM-CSF is an active therapeutic agent in our SCID mouse model of AML with a unique mechanism of action and differing toxicities than current cytotoxic agents.

Animals↗
PubMed1998

Malignant progenitors from patients with acute myelogenous leukemia are sensitive to a diphtheria toxin-granulocyte-macrophage colony-stimulating factor fusion protein.

We have previously demonstrated that human granulocyte-macrophage colony-stimulating factor (GM-CSF) fused to a truncated diphtheria toxin (DT388-GMCSF) kills acute myelogenous leukemia (AML) cell lines bearing the GM-CSF receptor. We now report that exposure of malignant cells from 50 different patients with AML for 48 hours in culture to DT388-GMCSF reduces by a median of 1.6 logs (range, 0 to 3.7 logs) the number of leukemic cells capable of forming colonies in semisolid media (leukemic colony-forming cells [CFU-L]) with a median IC50 of 3 x 10(-12) mol/L (range, 5 to >4,000 x 10(-12) mol/L). Furthermore, the cell kill is dependent on the presence of high-affinity GM-CSF receptors on leukemic blasts, because CFU-L from 27 of 28 AML samples expressing > or = 35 GM-CSF receptors per cell were inhibited by the toxin, whereas the colony growth from all 4 leukemic samples (2 AML, 1 acute lymphoblastic leukemia [ALL], and 1 prolymphocytic leukemia [PLL]) that had less than 35 receptors per cell was unaffected by the drug. Sensitivity of CFU-L to DT388-GMCSF was seen regardless of the clinical responsiveness of the patient's leukemia to standard chemotherapy agents. In contrast, clonogenic cells from normal bone marrow formed colonies at near control numbers after exposure to much higher toxin concentrations (4 x 10(-9) mol/L) than those required to kill CFU-L from most patients. Thus, leukemic progenitors isolated directly from the peripheral blood of most AML patients show the same sensitivity to DT388-GMCSF as previously demonstrated for AML cell lines. Under the same conditions of exposure, normal hematopoietic progenitors are relatively unaffected by DT388-GMCSF, suggesting its potential as a therapeutic agent in AML.

Adult↗
PubMed1998

Toxicology and pharmacokinetics of DT388-GM-CSF, a fusion toxin consisting of a truncated diphtheria toxin (DT388) linked to human granulocyte-macrophage colony-stimulating factor (GM-CSF) in C57BL/6 mice.

Because the majority of acute myeloid leukemia (AML) blasts express the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor, we are developing a fusion toxin consisting of a truncated diphtheria toxin (DT388) linked to human GM-CSF for multi-drug resistant AML. Our goal was to determine the toxicity and pharmacokinetics of DT388-GM-CSF in C57BL/6 mice. Because human GM-CSF does not cross-react with the mouse GM-CSF receptor, the toxicity observed should be nonspecific toxicity of DT388. We injected C57BL/6 mice i.p. with 0.1, 0.5, 1.0, 1.5, 1.75, 2.0, 3.5, 5.0, or 10 micrograms/day of DT388-GM-CSF for 5 consecutive days. For pharmacokinetics, blood samples were drawn at 20, 40, 60, 120, and 180 min after i.p. administration of 81 micrograms/kg of DT388-GM-CSF. In mice, the LD10 of DT388-GM-CSF is between 84.4 (1.5) and 104.4 (1.75) micrograms/kg (microgram) when administered for 5 consecutive days. All mice receiving > or = 201 micrograms/kg (3.5 micrograms) for 5 consecutive days died. Histopathologic examination of morbid animals showed only renal toxicity with acute proximal tubular necrosis. DT388-GM-CSF is stable in vivo based on nonreducing SDS-PAGE gel of plasma samples of 125I-labeled DT388-GM-CSF injected i.p.. The peak concentration of DT388-GM-CSF was 3.3 x 10(-8) M at 40 min and exhibited a t1/2 of 24 min. Based on its half-life, DT388-GM-CSF concentrations in the plasma are above the concentration inhibiting 50% protein synthesis and inducing apoptosis in 50% of HL-60 cells (AML cell line) for 5.2 h. Only four of 17 mice developed a weak immune response (0.9-160 ng/mL) 3 weeks after treatment. DT388-GM-CSF exhibits a short t1/2, but concentrations exceed those required in vitro to inhibit AML cell lines.

Animals↗
PubMed1998

Broadsheet number 47: Chronic hepatitis: an update with guidelines for histopathological assessment of liver biopsies. Board of Education of The Royal College of Pathologists of Australasia.

The liver biopsy remains the 'gold standard' for the diagnosis of chronic hepatitis, particularly since it is the only investigation that permits assessment of the severity (grade of histological activity and stage of fibrosis) of liver injury. As outlined below, the liver biopsy is invaluable for both diagnosis and the monitoring of therapy. To optimise the value of the liver biopsy, a standardised approach for assessment and reporting of chronic hepatitis is recommended.

Biopsy↗
PubMed1997

Modulation of the apoptotic response of human myeloid leukemia cells to a diphtheria toxin granulocyte-macrophage colony-stimulating factor fusion protein.

It has previously been shown that human granulocyte-macrophage colony-stimulating factor (GM-CSF) can be fused to a truncated diphtheria toxin (DT) to produce a recombinant fusion toxin that kills GM-CSF receptor-bearing cells. We now report that DT388-GM-CSF induces apoptosis and inhibition of colony formation in semisolid medium in receptor positive cells, and that the induction of apoptosis correlates with GM-CSF-receptor occupancy at low ligand concentrations. Also, the induction of apoptosis correlates with the inhibition of protein synthesis and is inversely related to the amount of intracellular antiapoptotic proteins (Bcl2 and Bc1XL). Nine myeloid leukemia cells lines and four nonmyeloid leukemia cell lines were incubated with 0.7 nmol/L of 125I-GM-CSF in the presence or absence of excess cold GM-CSF and bound label measured. High affinity receptor numbers varied from 0 to 291 molecules per cell. Cells were incubated with varying concentrations of recombinant fusion toxin for 48 hours and incorporation of 3H-leucine (protein synthesis), segmentation of nuclei after DAPI staining (apoptosis), and colony formation in 0.2% agarose (clonogenicity) were measured. DT388-GM-CSF at 4 x 10(-9) mol/L inhibited colony formation 1.5 to 3.0 logs for receptor positive cell lines. Protein synthesis and apoptosis IC50s varied among cell lines from greater than 4 x 10(-9) mol/L to 3 x 10(-13) mol/L. GM-CSF-receptor occupancy at 0.7 nmol/L GM-CSF-ligand concentration correlated with the protein synthesis IC50. Similarly, the protein synthesis inhibition and apoptosis induction correlated well, except in cells overexpressing Bcl2 and BclXL, in which 25- to 150-fold inhibition of apoptosis was observed. We conclude that DT388-GM-CSF can kill acute myeloid leukemia blasts but that apoptotic sensitivities will depend on the presence of at least 100 high affinity GM-CSF receptors/cell and the absence of overexpressed antiapoptotic proteins.

Apoptosis↗
PubMed1997

A phase I and pharmacokinetic study of high dose tamoxifen and weekly cisplatin in patients with metastatic melanoma.

BACKGROUND: The authors have previously demonstrated that tamoxifen (TAM) is synergistic with cisplatin (DDP) in patients with metastatic melanoma. In vitro studies have demonstrated that TAM/DDP synergy is dependent on a TAM effect that is currently under investigation. In an attempt to improve the complete response rate of this regimen, the authors initiated a Phase I trial to determine the maximum tolerated dose (MTD) of TAM that could be safely administered with weekly DDP. METHODS: TAM was started on Day 1 at a dose of 80 mg/day and was increased by 40 mg to the MTD in groups of 3 patients. DDP (80 mg/m2) was begun on Day 2 and repeated weekly for a total of 3 weeks. During Week 4, the patients were not treated with DDP but instead evaluated for response. If disease stabilization or regression was documented, the patients received a second 3-week cycle of DDP and were then reevaluated for response. Patients with progressive disease were removed from the study. RESULTS: In 25 consecutive patients, the overall response rate was 20%. No responses were observed in patients treated with TAM at a dose of <240 mg/day. Among 13 patients treated at or above this dose, there were 2 complete responses, 3 partial responses, 2 mixed responses, and 6 patients with progressive disease. The overall response rate for patients treated with 240 mg of TAM or higher was 38.5%. Dose-limiting toxicity, which occurred at a TAM dose of 280 mg/day, was primarily hematologic and gastrointestinal in nature. There was one toxic death (due to septic neutropenia) at this dose. There were no episodes of thrombosis. CONCLUSIONS: A TAM dose of 240 mg/day is the recommended Phase II dose. Based on the 38.5% overall response rate at this dose, the authors have initiated a Phase II study.

Adult↗
PubMed1997

Compatibility of filgrastim with selected antimicrobial drugs during simulated Y-site administration.

The compatibility of filgrastim with imipenem-cilastatin, ceftazidime, fluconazole, gentamicin, tobramycin, and amikacin was studied. Filgrastim 40 micrograms/mL or filgrastim 10 micrograms/mL (with human albumin) was combined with (1) imipenem-cilastatin 5 mg/mL (in terms of imipenem content), (2) ceftazidime 10 mg/mL (as the sodium salt), (3) fluconazole 2 mg/ mL, (4) gentamicin 1.6 mg/ mL (as the sulfate), (5) tobramycin 1.6 mg/mL (as the sulfate), or (6) amikacin 5 mg/ mL (as the sulfate). Equal volumes (5 mL) of the test-agent solutions were added in pairs to glass containers (simulating Y-site administration) in triplicate. Samples were analyzed for filgrastim activity, drug concentration, pH, and visible physical changes during storage at approximately 25 degrees C for up to four hours. Filgrastim activity was measured by the in vitro bioassay, and antimicrobial drug concentrations were measured by stability-indicating high-performance liquid chromatography or fluorescence polarization immunoassay. Filgrastim retained its activity, except for the combination of filgrastim at the lower concentration with gentamicin or at the higher concentration with imipenem-cilastatin. Antimicrobial drug concentrations did not change significantly during the study. No precipitation, color change, or haze was noted in any mixture. Changes in pH were negligible except for an increase in the mixture of filgrastim at either concentration with ceftazidime. In most cases, filgrastim retained its activity in the presence of a variety of antimicrobial drugs for up to four hours; in all cases, the antimicrobial drugs remained stable.

Anti-Infective Agents↗
PubMed1995

Biotransformation and hepatotoxicity of HCFC-123 in the guinea pig: potentiation of hepatic injury by prior glutathione depletion.

The chlorofluorocarbon substitute 1,1-dichloro-2,2,2-trifluoroethane (HCFC-123) is a structural analog of halothane. Both are oxidatively metabolized by CYP2EI, producing a reactive trifluoroacyl acid chloride intermediate and have been shown to cause acute liver necrosis in the guinea pig. With halothane, liver injury has been associated with the degree of reactive intermediate binding to hepatic protein. This injury can be potentiated by prior glutathione (GSH) depletion. Thus, the combination of GSH depletion and HCFC-123 exposure was evaluated for its hepatotoxic potential in this species. Male outbred Hartley guinea pigs were injected with either 0.8 g/kg l-buthionine-(S,R)-sulfoximine (BSO) to deplete hepatic glutathione or vehicle control solution 24 hr before a 4-hr inhalation exposure to 1.0% (v/v) HCFC-123 with 40% O2. HCFC-123 caused minimal liver injury with only 1 of 8 exposed animals displaying confluent zone 3 necrosis. GSH depletion potentiated injury producing submassive to massive liver necrosis in some animals. This potentiation was associated with a 36% increase in covalent binding of reactive HCFC-123 intermediates to hepatic protein. These results were not due to alterations in the biotransformation of HCFC-123 as indicated by plasma concentrations of the metabolites trifluoroacetic acid and fluoride ion which were not affected by BSO pretreatment. HCFC-123 was also found to cause a decrease in liver GSH concentrations following exposure. These findings demonstrate a role for hepatic GSH in helping to prevent covalent binding by the trifluoroacyl acid chloride intermediate. Inhalation of HCFC-123 can cause acute hepatic injury in the guinea pig that is worsened by low hepatic GSH concentrations.

Animals↗
PubMed1995

Development of tolerance to antinociceptive effects of an intrathecal morphine/clonidine combination in rats.

Previous animal studies have shown the antinociceptive effects of intrathecal clonidine and intrathecal morphine to be synergistic. This study investigated the intrathecal administration of multiple doses of this drug combination to examine the rate of development of tolerance and to determine whether there was any toxic effect on the spinal cord. Rats with indwelling intrathecal catheters were given saline, morphine (2.5-7.5 micrograms), clonidine (17.5 micrograms), or clonidine (17.5 micrograms) plus morphine (1 microgram) intrathecally twice daily for 4 1/2 days (total of 9 doses). Hot plate and tail flick tests were conducted after the first, fifth and ninth doses. After the ninth dose animals were killed and their spinal cords were removed for histological examination. Tolerance developed to the antinociceptive effects of the drug combination, but at a slower rate than to morphine alone. No evidence of toxicity or injury to the spinal cord was observed other than changes which could be ascribed to the presence of the catheter.

Animals↗
PubMed1995

Adjuvant therapy of node-negative breast cancer.

OBJECTIVE: To present the controversies regarding adjuvant cytotoxic chemotherapy or hormonal therapy in patients with node-negative breast cancer, and to evaluate the use of prognostic factors in identifying patients with node-negative breast cancer who will benefit from adjuvant therapy. DATA SOURCE: A MEDLINE search was performed to identify pertinent primary literature and review articles. Articles also were identified through Current Contents, textbooks, and bibliographies of selected articles. DATA EXTRACTION: The most recent clinical trials that evaluated cytotoxic chemotherapy or hormonal therapy in patients with node-negative breast cancer were chosen. Recent review articles and clinical trials that analyzed prognostic factors also were evaluated. DATA SYNTHESIS: The treatment of patients with node-negative breast cancer remains controversial. Approximately 60-80% of patients with this diagnosis will be alive 10 years after initial treatment without adjuvant therapy. The use of chemotherapy or hormonal therapy in node-negative disease increased after the 1988 National Cancer Institute Clinical Alert. Since that time, the research in node-negative breast cancer has focused on identifying prognostic factors and evaluating new treatment regimens. It is hoped that prognostic factors will help direct treatment decisions by identifying subgroups of patients who may benefit from adjuvant therapy. Prognostic factors currently being evaluated include tumor size, hormonal receptors, ploidy status, S-phase fraction, and cathepsin D. CONCLUSIONS: Many patients with node-negative breast cancer will be cured by local therapy alone. Even so, up to 58% of node-negative patients may develop recurrent disease. Reduction of breast cancer recurrence in patients with node-negative breast cancer has been documented as a result of adjuvant chemotherapy or tamoxifen. Of utmost priority is the identification of patients with node-negative breast cancer at highest risk for recurrence so that they may receive appropriate adjuvant therapy with curative intent, while sparing patients at lower risk for recurrence the toxic effects and financial burden incurred by unnecessary adjuvant treatment.

Breast Neoplasms↗