Relation of body mass index to tumor markers and survival among young women with invasive ductal breast carcinoma.

Background: Obesity has been shown to affect breast carcinoma prognosis, with the heaviest women having a higher mortality due to breast carcinoma. Few studies have focused on premenopausal women or the correlation of body mass index (BMI) to tumor characteristics related to prognosis.

Methods: The authors conducted a population-based follow-up study for mortality of 1177 women younger than 45 years of age who had invasive ductal breast carcinoma diagnosed from 1983 through 1992.

18fluorodeoxyglucose positron emission tomography to detect mediastinal or internal mammary metastases in breast cancer.

Purpose: To determine the prevalence of suspected disease in the mediastinum and internal mammary (IM) node chain by 18fluorodeoxyglucose (FDG) positron emission tomography (PET), compared with conventional staging by computed tomography (CT) in patients with recurrent or metastatic breast cancer.

Patients And Methods: We retrospectively evaluated intrathoracic lymph nodes using FDG PET and CT data in 73 consecutive patients with recurrent or metastatic breast cancer who had both CT and FDG PET within 30 days of each other. In reviews of CT scans, mediastinal nodes measuring 1 cm or greater in the short axis were considered positive.

[18F]fluoroestradiol radiation dosimetry in human PET studies.

Unlabelled: [18F]16alpha-fluoroestradiol (FES) is a PET imaging agent useful for the study of estrogen receptors in breast cancer. We estimated the radiation dosimetry for this tracer using data obtained in patient studies.

Methods: Time-dependent tissue concentrations of radioactivity were determined from blood samples and PET images in 49 patients (52 studies) after intravenous injection of FES.

Concurrent radiation therapy and paclitaxel or docetaxel chemotherapy in high-risk breast cancer.

Purpose: Evidence supports the inclusion of the taxanes in the treatment of breast cancer. A recent randomized trial has shown a survival advantage to the addition of paclitaxel in the adjuvant treatment of node-positive patients. Several studies have suggested diminished local control if adjuvant radiation is delayed, while in vitro and in vivo studies have demonstrated a benefit of concurrent administration of taxanes with radiation.

Dendritic cells lose ability to present protein antigen after stimulating antigen-specific T cell responses, despite upregulation of MHC class II expression.

Immature dendritic cells (DC) take up, process and present protein antigens; mature DC are specialized for stimulating primary T cell responses with increased expression of MHC class II and co-stimulatory molecules, but are incapable of processing and presenting soluble protein. The current study examined whether maturation of DC is triggered by T cell recognition of antigens presented by immature DC. Human DC derived from CD34+ progenitor cells by culture with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-6 (IL-6) in serum-free medium could prime naive CD4+ T cells to keyhole limpet hemocyanin (KLH) and ovalbumin (OVA).

A Multidisciplinary Approach to Locoregional Management of the Axilla for Primary Operable Breast Cancer.

BACKGROUND: Lymph node metastasis is the single most important factor in assessing breast cancer prognosis and planning systemic therapy. However, lymph node dissection portends significant morbidity, with little or no therapeutic benefit if the nodes prove to be negative for cancer. METHODS: The authors review indications for avoiding axillary dissection, and they analyze the results from lower-level axillary lymphadenectomy together with the morbidity from full axillary dissection.

Participation in breast cancer risk counseling among women with a family history.

Recent scientific breakthroughs in the genetics of breast cancer may have had effects on women's perceptions of risk and subsequent worry about breast cancer. Here, we present the rates of interest in counseling among women identified from diverse sources, their levels of cancer worry and perceived risk, and predictors of their agreement to participate in breast cancer risk counseling. Women were identified through breast cancer cases and through media offers.

Monitoring the response of patients with locally advanced breast carcinoma to neoadjuvant chemotherapy using [technetium 99m]-sestamibi scintimammography.

Background: Mammographic and physical examination assessments of the response of locally advanced breast carcinoma (LABC) to neoadjuvant therapy have been shown to be inaccurate. The authors studied the feasibility and accuracy of [technetium 99m]-sestamibi (MIBI) for monitoring the response of patients with LABC to neoadjuvant chemotherapy.

Methods: Patients receiving neoadjuvant chemotherapy for LABC underwent prone lateral scintimammography before therapy, after 2 months of therapy, and close to the completion of chemotherapy (presurgery) if chemotherapy continued for >3 months.

Infusional paclitaxel and weekly vinorelbine chemotherapy with concurrent filgrastim for metastatic breast cancer: high complete response rate in a phase I-II study of doxorubicin-treated patients.

Purpose: We investigated 96-hour paclitaxel infusion combined with weekly (days eight and 15) vinorelbine as salvage therapy for metastatic breast cancer in anthracycline-exposed patients. All patients received scheduled support with granulocyte colony-stimulating factor (G-CSF; filgrastim). Tumor response, toxicity, time to progression (TTP), and survival were assessed.

Value of combined FDG PET and MR imaging in the evaluation of suspected recurrent local-regional breast cancer: preliminary experience.

Purpose: To assess the performance and potential clinical effects of combined 2-[fluorine 18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) and magnetic resonance (MR) imaging of the axilla and brachial plexus in patients suspected of having local-regional breast cancer metastases.

Materials And Methods: Upper-body FDG PET and axillary and supraclavicular MR imaging were performed in 10 patients (age range, 45-71 years) with clinical findings suggestive of breast cancer metastases. Medical records were reviewed retrospectively.

Anthropometric and hormone effects of an eight-week exercise-diet intervention in breast cancer patients: results of a pilot study.

To assess the feasibility of an exercise-diet intervention in sedentary, overweight breast cancer patients, we conducted a pilot 8-week intervention. Recruitment letters and interest surveys were sent to 99 stage 1 or 2 breast cancer patients, ages 25-75 years, who were identified through two Seattle breast surgery practices and the University of Washington Breast Clinic. Ten patients were eligible and interested and were enrolled in the intervention, which consisted of thrice-weekly monitored aerobic exercise sessions and a low-fat (20% of calories from fat) diet.

High-titer HER-2/neu protein-specific antibody can be detected in patients with early-stage breast cancer.

Purpose: To evaluate HER-2/neu-specific antibody immunity in patients with breast cancer, to determine the rate of occurrence of serum antibodies to HER-2/neu in patients with breast cancer, and to relate the presence of specific immunity to overexpression of HER-2/neu protein in primary tumor.

Methods: The antibody response to HER-2/neu protein was analyzed in 107 newly diagnosed breast cancer patients. Sera was analyzed for the presence of HER-2/neu-specific antibodies with a capture enzyme-linked immunosorbent assay (ELISA) and verified by Western blot.

Induction of multiple anti-c-erbB-2 specificities accompanies a classical idiotypic cascade following 2B1 bispecific monoclonal antibody treatment.

The bispecific monoclonal antibody (bsmAb) 2B1, targeting the extracellular domain of c-erbB-2, the protein product of the HER-2/neu proto-ocogene, and Fc gamma RIII (CD16), expressed by human natural killer cells, neutrophils and differentiated monocytes, mediates the specific cytotoxic activity of these effector cells to tumor cells. A group of 24 patients with c-erbB-2-overexpressing tumors were treated with intravenously administered 2B1 in a phase I clinical trial and followed after treatment to evaluate the diversity and extent of the 2B1-induced humoral immune responses. As expected, 17 of 24 patients developed human anti-(murine Ig) antibodies (HAMA) to whole 2B1 IgG in a range from 100 ng/ml to more than 50000 ng/ml; 10 of these patients (42%) had strong (at least 1000 ng/ml) HAMA responses, some of which were still detectable at day 191.

Dose-intensive vinorelbine with concurrent granulocyte colony-stimulating factor support in paclitaxel-refractory metastatic breast cancer.

Purpose: We evaluated weekly single-agent intravenous (IV) vinorelbine as salvage therapy for metastatic breast cancer. After the first five patients, all received elective growth factor support with granulocyte colony-stimulating factor (G-CSF; filgrastim) in an attempt to maximize delivered dose-intensity (DDI). Objective tumor response, DDI, and toxicity were assessed, as well as time to progression (TTP) and survival.

Granulocyte-macrophage colony-stimulating factor: an effective adjuvant for protein and peptide-based vaccines.

The current studies evaluate granulocyte-macrophage colony-stimulating factor (GM-CSF) as a vaccine adjuvant. An important issue for developing vaccine therapy for human malignancy is identifying adjuvants that can elicit T-cell responses to proteins and peptides derived from "self" tumor antigens. GM-CSF, in vitro, stimulates the growth of antigen-presenting cells such as dendritic cells and macrophages.

Peptide-based, but not whole protein, vaccines elicit immunity to HER-2/neu, oncogenic self-protein.

HER-2/neu, an overexpressed oncogenic protein, has been proposed as a human cancer vaccine target. HER-2/neu is a "self" protein, however, and methods of vaccine strategies that would be effective in immunizing patients to a "self" tumor Ag have not been established. Many of the tumor Ags defined in humans are nonmutated self proteins, e.

Generation of immunostimulatory dendritic cells from human CD34+ hematopoietic progenitor cells of the bone marrow and peripheral blood.

Dendritic antigen-presenting cells are considered to be the most effective stimulators of T cell immunity. The use of dendritic cells has been proposed to generate therapeutic T cell responses to tumor antigens in cancer patients. One limitation is that the number of dendritic cells in peripheral blood is exceedingly low.

Immunity to the HER-2/neu oncogenic protein.

The study of oncogenic viruses led to the discovery that transforming retroviruses contain oncogenes homologous with and/or derived from cellular proto-oncogenes. In humans malignant transformation is often the result of the activation of proto-oncogenes. Normal proto-oncogenes can be activated to transforming proto-oncogenes by a variety of mechanisms including point mutation, translocation and amplification.

In vitro tests that predict tumor-associated idiotype levels in the serum of patients with B cell lymphomas and leukemias.

The presence of circulating tumor idiotype interferes with the in vivo effectiveness of anti-idiotype antibodies. We developed two assays that permit identification of patients with high levels of serum idiotype without the need for first producing an anti-idiotype antibody. A cell suspension made from the tumor was cultured for seven days with or without phytohemagglutin (PHA) and/or phorbol myristic acetate (PMA).

Studies on B lymphoid tumors treated with monoclonal anti-idiotype antibodies: correlation with clinical responses.

Monoclonal anti-idiotype antibodies can be made which are exquisitely specific for B lymphocytic malignancies. We have conducted a clinical trial in which some patients' tumors regressed after infusion of such antibodies. Here, we evaluated characteristics of the antibodies, the tumors, and the patients to determine which features best correlated with the clinical response.

Southern blot analysis of DNA extracted from formalin-fixed pathology specimens.

We have developed a method for the extraction of DNA from formalin-fixed, paraffin-embedded pathology specimens. High-molecular-weight DNA was recovered from well-fixed nonautolyzed samples of viable tissue. DNA recovered from samples exposed to picric acid or mercuric chloride containing fixatives was not intact.

The optimal application of forward and ninety-degree light scatter in flow cytometry for the gating of mononuclear cells.

Peripheral blood mononuclear cells from ten normal donors were labeled with a monoclonal antibody specific for monocytes and analyzed using a fluorescence activated cell sorter (FACS). Forward and 90 degrees light scatter parameters were studied in order to apply optimal computerized gating to identify and exclude monocytes from lymphocyte populations. An average of 9.

The induction of Leu-1 antigen expression in human malignant and normal B cells by phorbol myristic acetate (PMA).

Malignant cells from five patients with B cell leukemia or lymphoma were cultured with phorbol myristic acetate (PMA). PMA was found to induce cell surface expression of the Leu-1 antigen in cells from three of the five patients. Using one- and two-color immunofluorescence staining and flow cytometry, we have shown simultaneous expression of the Leu-1 antigen with other B cell markers.

Biclonal B-cell lymphoma.

The cells of most tumors are considered to be genetically homogeneous because they are assumed to represent a single clone descended from one abnormal cell. We have discovered three cases of B-cell lymphoma for which this generalization is not true. In each case, the tumor was composed of two subpopulations of cells, each expressing a different immunoglobulin molecule.