Genomic alterations associated with early stages of breast tumor metastasis.

Background: Molecular studies suggest that acquisition of metastatic potential occurs early in the development of breast cancer; mechanisms by which cells disseminate from the primary carcinomas and successfully colonize foreign tissues are, however, largely unknown. Thus, we examined levels and patterns of chromosomal alterations in primary breast tumors from node-negative (n = 114) and node-positive (n = 115) patients to determine whether specific genomic changes are associated with tumor metastasis.

Methods: Fifty-two genetic markers representing 26 chromosomal regions commonly altered in breast cancer were examined in laser microdissected tumor samples to assess levels and patterns of allelic imbalance (AI).

Metastatic carcinoid tumour presenting as hepatic encephalopathy.

Background: Hepatic encephalopathy is rarely encountered with carcinoid syndrome, but massive hepatic replacement by carcinoid tumour can cause neuropsychiatric alterations.

Case Outline: A man of 42 years presented with carcinoid syndrome accompanied by features of hepatic encephalopathy. Following extended right hepatectomy his mental status returned to normal in line with markers of hepatic failure.

Comorbidity of substance dependence and depression: role of life stress and self-efficacy in sustaining abstinence.

The authors examined life stress and self-efficacy as predictors of time to relapse for 113 adults with comorbid major depressive disorder and alcohol and/or substance dependence in a randomized clinical trial comparing 2 psychotherapy interventions (integrated cognitive- behavioral therapy and 12-step facilitation therapy). Life stress, self-efficacy, and substance use were assessed at treatment entry, 12 weeks (mid-treatment), and 24 weeks (end of treatment). Time to relapse was defined as the number of days from treatment initiation until first alcohol and/or drug use.

A Bayesian derived network of breast pathology co-occurrence.

In this paper, we present the validation and verification of a machine-learning based Bayesian network of breast pathology co-occurrence. The present/not present occurrences of 29 common breast pathologies from 1631 pathology reports were used to build the network. All pathology reports were developed by a single pathologist.

The genomic heritage of lymph node metastases: implications for clinical management of patients with breast cancer.

Background: Metastatic breast cancer is an aggressive disease associated with recurrence and decreased survival. To improve outcomes and develop more effective treatment strategies for patients with breast cancer, it is important to understand the molecular mechanisms underlying metastasis.

Methods: We used allelic imbalance (AI) to determine the molecular heritage of primary breast tumors and corresponding metastases to the axillary lymph nodes.

Electrical impedance scanning as a new breast cancer risk stratification tool for young women.

Background: Electrical impedance scanning (EIS) measures changes in breast tissue associated with breast cancer (Br-Ca) development. The T-Scan(tm2000 (ED is designed to use EIS to identify women ages 30-39 with elevated risk of breast cancer (i.e.

HYOU1/Orp150 expression in breast cancer.

Background: Heat shock protein HYOU1, alternatively known as Orp150, plays an important role in hypoxia/ischemia and angiogenesis. Preliminary studies demonstrated increased HYOU1/Orp150 expression in prostate, bladder and invasive breast cancer. This study further evaluates HYOU1/Orp150 expression in different stages of breast cancer such as benign, pre-malignant and malignant lesions, and correlates it with clinical and pathological data.

The Clinical Breast Care Project: an important resource in investigating environmental and genetic contributions to breast cancer in African American women.

Age at diagnosis, pathological characteristics, and tumor behavior differ between African American (AAW) and Caucasian women (CW) with breast cancer, with AAW having more aggressive tumors and higher mortality rates. Although both societal and molecular contributions to these disparities have been suggested, the African American population has traditionally been under-represented in research and clinical protocols, limiting the power of epidemiologic and molecular studies to provide better understanding of disease pathogenesis in this minority population. The Clinical Breast Care Project (CBCP) has developed a large tissue and blood repository from patients undergoing treatment for breast cancer, with previous history of breast cancer, counseled in the Risk Reduction Clinic, screened by routine mammography, or undergoing elective reductive mammoplasty.

Breast cancer screening compliance among young women in a free access healthcare system.

Background And Objectives: To examine mammographic screening compliance among young military healthcare beneficiaries and to examine factors related to one time and recent mammographic compliance.

Methods: Medical records were reviewed for 1,073 subjects (age 41-47) recording dates of the two most recent screening mammograms. Examined outcomes were: whether the woman ever had mammography and, if so, whether she had a mammogram within 400 days.

Satisfaction with breast cancer screening and future screening participation.

Background: To measure satisfaction with an investigational breast cancer risk screening technique [electrical impedance scanning (EIS)] and to investigate the relationship between satisfaction and willingness to return for follow-up examination one year later.

Material/methods: 2727 women volunteers (age 18-45 years, military healthcare beneficiaries) underwent an EIS exam [reported as "negative" (average risk) or "positive" (high risk)]; then they filled out a questionnaire assessing satisfaction with the procedure. One year later, women were invited for follow-up screening.

Genomic instability and the development of metastatic lymph node tumors.

Background: Although recent data suggest that cells with metastatic potential disseminate from the primary breast tumor early in tumor development, the mechanism by which disseminated breast cancer cells proliferate within foreign tissues is not well understood. Here, we examined levels and patterns of allelic imbalance (AI) in metastatic lymph node (LN) tumors to identify molecular signals that promote the survival and growth of disseminated breast tumor cells.

Methods: DNA from 106 metastatic LN tumors from 25 patients was isolated after laser microdissection of pure tumor cell populations.

Correlation of levels and patterns of genomic instability with histological grading of DCIS.

Background: Histological grading of ductal carcinoma-in-situ (DCIS) lesions separates DCIS into three subgroups (well-, moderately, or poorly differentiated). It is unclear, however, whether breast disease progresses along a histological continuum or whether each grade represents a separate disease. In this study, levels and patterns of allelic imbalance (AI) were examined in DCIS lesions to develop molecular models that can distinguish pathological classifications of DCIS.

Prospective randomized study comparing sentinel lymph node evaluation with standard pathologic evaluation for the staging of colon carcinoma: results from the United States Military Cancer Institute Clinical Trials Group Study GI-01.

Background: The principal role of sentinel lymph node (SLN) sampling and ultrastaging in colon cancer is enhanced staging accuracy. The utility of this technique for patients with colon cancer remains controversial.

Purpose: This multicenter randomized trial was conducted to determine if focused assessment of the SLN with step sectioning and immunohistochemistry (IHC) enhances the ability to stage the regional nodal basin over conventional histopathology in patients with resectable colon cancer.

Breast, colorectal, and skin cancer screening practices and family history of cancer in U.S. women.

Background: Several national medical organizations recommend more intensive screening or screening at an earlier age for individuals with a family history of breast, colorectal, or skin cancer. This study examined whether women with a family history of cancer were more likely to use breast, colorectal, or skin cancer screenings compared with those without such a family history.

Methods: The data for this study came from female respondents who participated in the 2000 National Health Interview Survey.

Correlation of levels and patterns of genomic instability with histological grading of invasive breast tumors.

Pathological grade is a useful prognostic factor for stratifying breast cancer patients into favorable (well-differentiated tumors) and less favorable (poorly-differentiated tumors) outcome groups. The current system of tumor grading, however, is subjective and a large proportion of tumors are characterized as intermediate-grade tumors, making determination of optimal treatments difficult. To determine whether molecular profiles can discriminate breast disease by grade, patterns and levels of allelic imbalance (AI) at 26 chromosomal regions frequently altered in breast disease were examined in 185 laser microdissected specimens representing well-differentiated (grade 1; n = 55), moderately-differentiated (grade 2; n = 71), and poorly-differentiated (grade 3; n = 59) stage I-IV breast tumors.

Functional identity of genes detectable in expression profiling assays following globin mRNA reduction of peripheral blood samples.

Objectives: Whole-blood RNA for microarray analysis is easily accessible but contains a large proportion of globin mRNA that interferes with the accurate assessment of other genes. This study investigated the biological significance of genes whose expression was unmasked by globin mRNA reduction in peripheral blood.

Design And Methods: Samples were collected from healthy subjects using the PAXgene Blood RNA System, and globin mRNA was depleted using GLOBINclear.

Assessing serum cytokine profiles in breast cancer patients receiving a HER2/neu vaccine using Luminex technology.

We used the Luminex assay to compare serum cytokine profiles of breast cancer patients (BCa) to healthy controls, node-positive (NP) patients to node-negative (NN), and pre- and post-vaccination serum of BCa vaccinated with a HER2/neu E75 peptide vaccine. Sera from 36 pre- and post-vaccination BCa, (12 NP and 24 NN) and 13 healthy, female donors, were evaluated using Luminex technology. Levels of 22 cytokines consisting of interleukin (IL)-1alpha, -1beta, -2, -4, -5, -6, -7, -8, -10, -12, -13, -15, -17, IFN-gamma, G-CSF, GM-CSF, TNF-alpha, IP-10, MIP-1alpha, RANTES, eotaxin and monocyte chemotactic protein-1 (MCP-1) were assessed.

Detecting outlier microarray arrays by correlation and percentage of outliers spots.

We developed a quality assurance (QA) tool, namely microarray outlier filter (MOF), and have applied it to our microarray datasets for the identification of problematic arrays. Our approach is based on the comparison of the arrays using the correlation coefficient and the number of outlier spots generated on each array to reveal outlier arrays. For a human universal reference (HUR) dataset, which is used as a technical control in our standard hybridization procedure, 3 outlier arrays were identified out of 35 experiments.

Co-occurrence analysis for discovery of novel breast cancer pathology patterns.

To discover novel patterns in pathology co-occurrence, we have developed algorithms to analyze and visualize pathology co-occurrence. With access to a database of pathology reports, collected under a single protocol and reviewed by a single pathologist, we can conduct an analysis greater in its scope than previous studies looking at breast pathology co-occurrence. Because this data set is unique, specialized methods for pathology co-occurrence analysis and visualization are developed.

Investigating the combination of trastuzumab and HER2/neu peptide vaccines for the treatment of breast cancer.

Background: Trastuzumab, an anti-HER2/neu monoclonal antibody, is thought to promote HER2/neu receptor internalization and/or turnover. This study was designed to investigate the kinetics of trastuzumab treatment on tumor cells with varying levels of HER2/neu expression and to determine the effect of trastuzumab on HER2/neu-specific cytotoxic T lymphocyte-mediated lysis.

Methods: Three cell lines with varying levels of HER2/neu expression were incubated with varying doses of trastuzumab at multiple time points.

Factors associated with the incompliance with mammogram screening among individuals with a family history of breast cancer or ovarian cancer.

Objective: The national guidelines recommend more intensive screening for breast cancer for women with a family history of breast or ovarian cancer. Using the data from the 2000 National Health Interview Survey (NHIS), we examined factors related to the underuse of mammogram in this population.

Method: The study subjects were 1,215 women aged 30-79 who had a family history of breast or ovarian cancer in their first-degree relatives.

Analysis of naïve and memory CD4 and CD8 T cell populations in breast cancer patients receiving a HER2/neu peptide (E75) and GM-CSF vaccine.

We are conducting clinical trials of the E75 peptide as a vaccine in breast cancer (BrCa) patients. We assessed T cell subpopulations in BrCa patients before and after E75 vaccination and compared them to healthy controls. We obtained 17 samples of blood from ten healthy individuals and samples from 22 BrCa patients prior to vaccination.

Analysis of metabolic and regulatory pathways through Gene Ontology-derived semantic similarity measures.

This study investigates the feasibility of applying Gene Ontology (GO)-derived semantic similarity methods to the biological pathway analysis. The results derived from the analysis of human metabolic and regulatory pathways are consistent with the network biology. It suggests that the semantic similarity measurement may be used to help the pathway modeling.

Levels of circulating regulatory CD4+CD25+ T cells are decreased in breast cancer patients after vaccination with a HER2/neu peptide (E75) and GM-CSF vaccine.

Purpose: We are conducting clinical trials in breast cancer (BrCa) patients to test the HER2/neu peptide vaccine (E75). We have investigated the impact of this vaccine on circulating levels of regulatory T cells (Treg) and the resulting effects on antitumor responses.

Experimental Design: Twenty-two blood samples from healthy individuals and from 22 BrCa patients including pre- and post-vaccination samples from seven vaccinated HLA-A2+ patients were stained for CD4, CD25, and CD69 as well as CD8 and E75:HLA-A2 Ig dimer and quantified by flow cytometry.