Low Z-4OHtam concentrations are associated with adverse clinical outcome among early stage premenopausal breast cancer patients treated with adjuvant tamoxifen.

Low steady-state levels of active tamoxifen metabolites have been associated with inferior treatment outcomes. In this retrospective analysis of 406 estrogen receptor-positive breast cancer (BC) patients receiving adjuvant tamoxifen as initial treatment, we have associated our previously reported thresholds for the two active metabolites, Z-endoxifen and Z-4-hydroxy-tamoxifen (Z-4OHtam), with treatment outcomes in an independent cohort of BC patients. Among all patients, metabolite levels did not affect survival.

NR2F1 stratifies dormant disseminated tumor cells in breast cancer patients.

Background: The presence of disseminated tumor cells (DTCs) in bone marrow (BM) is an independent prognostic factor in early breast cancer but does not uniformly predict outcome. Tumor cells can persist in a quiescent state over time, but clinical studies of markers predicting the awakening potential of DTCs are lacking. Recently, experiments have shown that NR2F1 (COUP-TF1) plays a key role in dormancy signaling.

Prognostic significance of S100A4-expression and subcellular localization in early-stage breast cancer.

Purpose: Prognostic factors are useful in order to identify early-stage breast cancer patients who might benefit from adjuvant treatment. The metastasis-promoting protein S100A4 has previously been associated with poor prognosis in breast cancer patients. The protein is expressed in diverse subcellular compartments, including the cytoplasm, extracellular space, and nucleus.

Clinical outcome with correlation to disseminated tumor cell (DTC) status after DTC-guided secondary adjuvant treatment with docetaxel in early breast cancer.

Purpose: The presence of disseminated tumor cells (DTCs) in bone marrow (BM) predicts survival in early breast cancer. This study explores the use of DTCs for identification of patients insufficiently treated with adjuvant therapy so they can be offered secondary adjuvant treatment and the subsequent surrogate marker potential of DTCs for outcome determination.

Patients And Methods: Patients with early breast cancer who had completed six cycles of adjuvant fluorouracil, epirubicin, and cyclophosphamide (FEC) chemotherapy underwent BM aspiration 2 to 3 months (BM1) and 8 to 9 months (BM2) after FEC.

Comparison of molecular and immunocytochemical methods for detection of disseminated tumor cells in bone marrow from early breast cancer patients.

Background: Disseminated tumor cells (DTCs) have potential to predict the effect of adjuvant treatment. The purpose of this study was to compare two methods, reverse transcription quantitative PCR (RT-qPCR) and immunocytochemisty (ICC), for detecting breast cancer DTCs in bone marrow (BM) from early breast cancer patients.

Methods: We investigated a subset (n = 313) of BM samples obtained from 271 early breast cancer patients in the "Secondary Adjuvant Taxotere Treatment" (SATT)-trial.

Disseminated tumor cells as selection marker and monitoring tool for secondary adjuvant treatment in early breast cancer. Descriptive results from an intervention study.

Background: Presence of disseminated tumor cells (DTCs) in bone marrow (BM) after completion of systemic adjuvant treatment predicts reduced survival in breast cancer. The present study explores the use of DTCs to identify adjuvant insufficiently treated patients to be offered secondary adjuvant treatment intervention, and as a surrogate marker for therapy response.

Methods: A total of 1121 patients with pN1-3 or pT1c/T2G2-3pN0-status were enrolled.

Expression of cyclooxygenase-2 in invasive breast carcinomas and its prognostic impact.

Representative tumour sections from 468 patients with invasive breast cancer were immunostained for cyclooxygenase-2 (COX-2) and evaluated. The relationships between COX-2 expression, clinical outcome and various clinicopathological variables, including tumour vascularity and disseminated tumour cells (DTC) in the bone marrow were examined. COX-2 expression in invasive breast carcinoma cells was positively associated with oestrogen receptor and/or progesterone receptor positivity (p<0.

Combined analysis of vascular invasion, grade, HER2 and Ki67 expression identifies early breast cancer patients with questionable benefit of systemic adjuvant therapy.

Introduction: Over-treatment of low-risk early breast cancer patients with adjuvant systemic therapies is an important clinical challenge. Better techniques are required which can be used to distinguish between the large group of patients with no residual disease after surgery and consequently no benefit of adjuvant treatment, from the smaller group with high relapse risk. A better integration of available prognostic factors might contribute to improved prediction of clinical outcome.

Expression of vascular endothelial growth factor and vascular endothelial growth factor receptors 1 and 2 in invasive breast carcinoma: prognostic significance and relationship with markers for aggressiveness.

Aims: Vascular endothelial growth factor (VEGF), VEGF receptor 1 (VEGFR-1) and VEGF receptor 2 (VEGFR-2) play a role in breast cancer growth and angiogenesis. We examined the expression and relationship with clinical outcome and other prognostic factors.

Methods And Results: Tumour sections from 468 breast cancer patients were immunostained for VEGF, VEGFR-1, and VEGFR-2, and their relationships with tumour vascularity, disseminated tumour cells (DTCs) in bone marrow and other clinicopathological parameters were evaluated.

The prognostic significance of tumour cell detection in the peripheral blood versus the bone marrow in 733 early-stage breast cancer patients.

Introduction: The detection of circulating tumour cells (CTCs) in the peripheral blood and disseminated tumour cells (DTCs) in the bone marrow are promising prognostic tools for risk stratification in early breast cancer. There is, however, a need for further validation of these techniques in larger patient cohorts with adequate follow-up periods.

Methods: We assayed CTCs and DTCs at primary surgery in 733 stage I or II breast cancer patients with a median follow-up time of 7.

Persistence of disseminated tumor cells in the bone marrow of breast cancer patients predicts increased risk for relapse--a European pooled analysis.

Background: The prognostic significance of disseminated tumor cells (DTC) in bone marrow (BM) of breast cancer patients at the time of primary diagnosis has been confirmed by a large pooled analysis. In view of the lack of early indicators for secondary adjuvant treatment, we here evaluated whether the persistence of DTCs after adjuvant therapy increases the risk of subsequent relapse and death.

Patients And Methods: Individual patient data from 676 women with primary diagnosis of early breast cancer stages I-III from 3 follow-up studies were pooled.

DNA methylation patterns in luminal breast cancers differ from non-luminal subtypes and can identify relapse risk independent of other clinical variables.

The diversity of breast cancers reflects variations in underlying biology and affects the clinical implications for patients. Gene expression studies have identified five major subtypes- Luminal A, Luminal B, basal-like, ErbB2+ and Normal-Like. We set out to determine the role of DNA methylation in subtypes by performing genome-wide scans of CpG methylation in breast cancer samples with known expression-based subtypes.

Detection and clinical relevance of early disseminated breast cancer cells depend on their cytokeratin expression pattern.

The factors determining the clinical relevance of disseminated tumor cells (DTC) in breast cancer patients are largely unknown. Here we compared the specificity and clinical performance of two antibodies frequently used for DTC detection. Reactivities of antibodies A45-B/B3 (A45) and AE1/AE3 (AE) for selected cytokeratins (CK) were assessed by 2-DE Western Blot analysis.

Breast carcinoma vascularity: a comparison of manual microvessel count and Chalkley count.

Manual counting of microvessels as intratumoral microvessel density (MVD) and Chalkley counting have been used in several studies to assess the prognostic impact of vascularity in invasive breast carcinomas. In our present study, the aim was to evaluate the prognostic value of angiogenesis in invasive breast carcinoma assessed by MVD and Chalkley techniques in the same series of patients. A total of 498 breast carcinoma patients with median follow up time 85 months were evaluated.

The prognostic impact of occult nodal metastasis in early breast carcinoma.

The clinical relevance of isolated tumor cell (ITC: 0.2-2.

Vascularization in primary breast carcinomas: its prognostic significance and relationship with tumor cell dissemination.

Purpose: The interaction between tumor cells, stroma, and endothelial cells is important for the dissemination of tumor cells. The aim of the present study is to examine vascularity in primary breast carcinomas and its prognostic significance and relationship with tumor cell dissemination.

Experimental Design: A total of 498 invasive breast carcinomas were analyzed.

Presence of bone marrow micrometastasis is associated with different recurrence risk within molecular subtypes of breast cancer.

Expression profiles of primary breast tumors were investigated in relation to disseminated tumor cells (DTCs) in bone marrow (BM) in order to increase our understanding of the dissemination process. Tumors were classified into five pre-defined molecular subtypes, and presence of DTC identified (at median 85 months follow-up) a subgroup of luminal A patients with particular poor outcome (p=0.008).

Recurrent group A Streptococcal genital infection after Puerperal sepsis.

Recurrent group A streptococcal infection is a well-known phenomenon. It is well documented as a problem in pharyngotonsillitis and skin infections. This report describes a case of recurrent genital infection after puerperal sepsis caused by group A streptococci.