A phase I/II trial of epirubicin and docetaxel in locally advanced breast cancer (LABC) on 2-weekly or 3-weekly schedules: NCIC CTG MA.22.

This phase I/II neoadjuvant trial (ClinicalTrials.gov identifier NCT00066443) determined maximally-tolerated doses (MTD), dose-limiting toxicities, response-to-therapy, and explored the role of novel response biomarkers. MA.

Diagnostic performance of quantitative shear wave elastography in the evaluation of solid breast masses: determination of the most discriminatory parameter.

Objective: The purpose of this article is to assess the diagnostic performance of quantitative shear wave elastography in the evaluation of solid breast masses and to determine the most discriminatory parameter.

Subjects And Methods: B-mode ultrasound and shear wave elastography were performed before core biopsy of 123 masses in 112 women. The diagnostic performance of ultrasound and quantitative shear wave elastography parameters (mean elasticity, maximum elasticity, and elasticity ratio) were compared.

Phase I trial of intraoperative detection of tumor margins in patients with HER2-positive carcinoma of the breast following administration of 111In-DTPA-trastuzumab Fab fragments.

Introduction: Our aim was to conduct a Phase I clinical trial to determine the feasibility of intraoperative detection of tumor margins in HER2 positive breast carcinoma using a hand-held γ-probe following administration of (111)In-DTPA-trastuzumab Fab fragments. Accurate delineation of tumor margins is important for preventing local recurrence.

Methods: Six patients with HER2-positive in situ or invasive ductal carcinoma were administered 74MBq (0.

D2-40 is expressed on the luminal surface of pulmonary airspaces in normal developing and adult lung but is lost in conditions associated with intra-alveolar infiltrates.

The D2-40 antigen is a glycosylated sialomucin that is strongly expressed by lymphatic endothelial cells. Recently we observed the expression of D2-40 on the luminal surface of pulmonary airspaces in lung sections. The aim of the study was to assess the expression of D2-40 antigen in normal lung development and in various pathologic conditions in which abnormal alveolar infiltrates were present.

IGFBP7 reduces breast tumor growth by induction of senescence and apoptosis pathways.

Insulin-like growth factor binding protein 7 (IGFBP7) has been shown to be a tumor suppressor in a variety of cancers. We previously have shown that IGFBP7 expression is inversely correlated with disease progression and poor outcome in breast cancer. Overexpression of IGFBP7 in MDA-MB-468, a triple-negative breast cancer (TNBC) cell line, resulted in inhibition of growth and migration.

Association of low tumor RNA integrity with response to chemotherapy in breast cancer patients.

The CAN-NCIC-MA22 phase I/II clinical trial evaluated women with locally advanced or inflammatory breast cancer treated with epirubicin and docetaxel at 2 or 3 weekly intervals in sequential cohorts. The relationship between various biomarkers and treatment response was assessed. Breast biopsy cores were obtained from 50 patients pre-, mid-, and post-treatment.

A human bone NOD/SCID mouse model to distinguish metastatic potential in primary breast cancers.

In this study, we created a clinically relevant model using NOD/SCID mice engrafted with human bone fragments in both right and left flanks, and show that the human bone implants are viable and functional for more than 6 mo. To investigate the growth and metastatic behavior of breast cancer, human primary breast tumor specimens were transplanted into human bone grafts under only the right flanks of the human-bone NOD/SCID mice. Some of the engrafted tumors proliferated extensively with massive neo-vascularization and also metastasized to the initially tumor-free left flank bone grafts.

Lymphatic invasion identified by monoclonal antibody D2-40, younger age, and ulceration: predictors of sentinel lymph node involvement in primary cutaneous melanoma.

Objectives: To assess whether lymphatic invasion identified by immunostaining with monoclonal antibody (Mab) D2-40 in primary cutaneous melanomas correlates with other clinicopathologic factors and to assess whether lymphatic invasion is a potential predictor of sentinel lymph node (SLN) status.

Design: Retrospective case-series study.

Setting: Academic referral center.

Biological Markers Predictive of Invasive Recurrence in DCIS.

DCIS is a heterogeneous group of non-invasive cancers of the breast characterized by various degrees of differentiation and unpredictable propensity for transformation into invasive carcinoma. We examined the expression and prognostic value of 9 biological markers with a potential role in tumor progression in 133 patients with pure DCIS treated with breast conserving surgery alone, between 1982-2000. Histology was reviewed and immunohistochemical staining was performed.

Breast metastasis by medullary thyroid carcinoma detected by FDG positron emission tomography.

Medullary thyroid carcinoma (MTC) is an uncommon thyroid cancer comprising 5% to 8% of thyroid neoplasms. In contrast to common thyroid tumors, this tumor originates from the calcitonin-producing C cells. Regional metastases to cervical lymph nodes occur early in the disease, whereas distant metastasis occurs late.

Breast cancer metastasis in a human bone NOD/SCID mouse model.

A major dilemma facing patients with breast cancer is how to decide between over treating indolent tumors and failing to adequately treat aggressive, potentially lethal cancers. Determination of the metastatic potential of a patient's breast cancer would clearly help guide those treatment decisions. Breast cancer commonly spreads to bone in 70% of women with advanced disease.

Intratumoral heterogeneity of HER2/neu in breast cancer--a rare event.

HER2/neu is overexpressed in about 20% of invasive breast carcinomas. Numerous studies have shown that there is high level of concordance between the HER2/neu status of the primary breast cancer and the metastases of a given patient. Recently, changes in HER2/neu status with tumor progression have been reported, suggesting the possibility of an emerging different tumor clone.

p27 phosphorylation by Src regulates inhibition of cyclin E-Cdk2.

The kinase inhibitor p27Kip1 regulates the G1 cell cycle phase. Here, we present data indicating that the oncogenic kinase Src regulates p27 stability through phosphorylation of p27 at tyrosine 74 and tyrosine 88. Src inhibitors increase cellular p27 stability, and Src overexpression accelerates p27 proteolysis.

Significance of lymph vessel invasion identified by the endothelial lymphatic marker D2-40 in node negative breast cancer.

Monoclonal antibody D2-40, a marker of lymphatic endothelium, identifies tumor emboli in lymph vessels. The aim of the study was to assess whether D2-40+ lymph vessel invasion (LVI) correlates with clinicopathologic factors including lymphovascular invasion (LVI) as assessed by haematoxylin and eosin-stained sections (H&E+ or H&E-) and to assess the prognostic significance in node-negative breast cancer. The study group consisted of 303 node-negative breast cancer patients that had a median follow-up of 7.

Biological significance of occult micrometastases in histologically negative axillary lymph nodes in breast cancer patients using the recent American Joint Committee on Cancer breast cancer staging system.

The biological significance of occult metastases in axillary lymph nodes of breast cancer patients is controversial. The purpose of the study was to determine the prognostic significance of occult micrometastases using the current American Joint Committee on Cancer (AJCC) staging system in a cohort of women with node-negative breast cancer, of whom 5% received adjuvant systemic therapy and who all had long-term follow-up. We studied a cohort of 214 consecutive histologically node-negative breast cancer patients with a median follow-up of 8 years.

Analysis of the HER2/neu gene amplification in microdissected breast cancer tumour samples.

The HER2/neu oncogene has been reported to be amplified in > 20% of invasive ductal carcinomas. In order to investigate the HER2/neu status in pure populations of breast cancer cells, a laser capture microdissection (LCM) system was used. Formalin-fixed paraffin-embedded breast tissue areas corresponding to normal ducts, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) were microdissected and genomic DNA was isolated by a modified proteinase K- phenol extraction method and subjected to PCR for HER2/neu analysis.

Prognostic significance of circulating tumour cells enumerated after filtration enrichment in early and metastatic breast cancer patients.

Background: We previously found a higher incidence of circulating tumour cells (CTCs) in women with metastatic breast cancer compared to early disease. In this study, we present follow-up data to explore the prognostic significance of these findings.

Methods: CTCs were quantified by immunostaining and direct visualization after centrifugation and filtration enrichment of peripheral blood from 131 patients.

Ascertaining prognosis for breast cancer in node-negative patients with innovative survival analysis.

Clinical decisions to administer adjuvant systemic therapy to women with early breast cancer require knowledge about baseline prognosis, which is only assessable in the absence of such adjuvant treatment, which most patients currently do receive. The Cox model is the standard tool for assessing the effect of prognostic factors; however, there may be substantive differences in the estimated prognosis obtained by the Cox model rather than a log-normal model. For more than 50 years, clinical breast cancer data for cohorts of patients have supported the choice of a log-normal model.

A novel RING-type ubiquitin ligase breast cancer-associated gene 2 correlates with outcome in invasive breast cancer.

The RING finger family of proteins possess ubiquitin ligase activity and play pivotal roles in protein degradation and receptor-mediated endocytosis. In this study, we examined whether the breast cancer-associated gene 2 (BCA2), a novel RING domain protein, has E3 ubiquitin ligase activity and investigated its expression status in breast tumors. The full-length BCA2 gene was cloned from the human breast cancer cell line MDA-MB-468.

Etiologic factors associated with p53 immunostaining in cutaneousmalignant melanoma.

Findings from a case-control study of cutaneous malignant melanoma (CMM) in Queensland, Australia, suggest that melanomas exhibiting p53 immunostaining possess different risk factors from those of other melanomas. To further explore this hypothesis, a case-only analysis of risk factors for p53 immunostaining with anti-p53 MAb DO-7 was undertaken in 523 people diagnosed with CMM in Canada and Australia. Phenotypic factors and past sun exposure were measured using a self-administered questionnaire and telephone interview.

Detection of lymphatic invasion in primary melanoma with monoclonal antibody D2-40: a new selective immunohistochemical marker of lymphatic endothelium.

Objectives: To identify the presence of lymphatic invasion in primary cutaneous melanoma using monoclonal antibody D2-40, a marker of lymphatic endothelium, and to correlate the presence of lymphatic invasion with other clinicopathologic characteristics of the tumors.

Design: Retrospective melanoma case series study comparing conventional hematoxylin-eosin staining with D2-40 immunostaining for detection of lymphatic invasion.

Setting: Departments of Pathology and Dermatology, Sunnybrook and Women's College Health Sciences Center, University of Toronto, Toronto, Ontario.

Imaging of HER2/neu-positive BT-474 human breast cancer xenografts in athymic mice using (111)In-trastuzumab (Herceptin) Fab fragments.

Trastuzumab (Herceptin) Fab were prepared by digestion of intact IgG with immobilized papain, derivatized with diethylenetriaminepentaacetic acid (DTPA) and radiolabeled with (111)In. The dissociation constant (Kd) for binding of Fab to HER2/neu-positive SK-BR-3 human breast cancer cells was two- to threefold higher than for intact IgG (14-36 vs. 8-14 nM).

Prognostic factors affecting the natural history of node-negative breast cancer.

Purpose: We undertook a natural history investigation of a broad selection of prognostic factors in a cohort of women with node-negative breast cancer.

Patients And Methods: The cohort consisted of 415 consecutive histologic node-negative (T1-3, M0) patients, operated on for primary breast cancer at Women's College Hospital, Toronto, Canada, between 1977 and 1986. Only 7% of these patients were given adjuvant systemic therapy; further, for the 48% of women who underwent lumpectomy, only 29% received adjuvant radiotherapy to the breast.

Enumeration of circulating tumor cells in the blood of breast cancer patients after filtration enrichment: correlation with disease stage.

The biological and clinical significance of circulating tumor cells (CTC) in the peripheral blood of breast cancer patients is not known. To study this question, we used a direct visualization assay to correlate the number of CTC with disease stage and progression. The CTC were enriched from the nucleated cell fraction by filtration and enumerated visually following immunostaining with anti-cytokeratin 8 (CK8) antibody CAM 5.

Characterization of a novel human breast cancer associated gene (BCA3) encoding an alternatively spliced proline-rich protein.

As part of an integrated study of breast cancer gene expression, partial cDNAs were cloned from normal and tumor breast cells by subtractive-hybridization and differential display cloning. The DNA sequence for one of these breast cancer associated genes was used to construct the larger 1319 bp BCA3 cDNA sequence using ESTs without assigned names or functions. High-level BCA3 mRNA expression was found in breast and prostate tumor cell lines whereas normal breast and prostate tissues have low-level expression.