Precise correlation between MRI and histopathology - exploring treatment margins for MRI-guided localized breast cancer therapy.

Background: Magnetic resonance imaging (MRI) is more often considered to guide, evaluate or select patients for partial breast irradiation (PBI) or minimally invasive therapy. Safe treatment margins around the MRI-visible lesion (MRI-GTV) are needed to account for surrounding subclinical occult disease.

Purpose: To precisely compare MRI findings with histopathology, and to obtain detailed knowledge about type, rate, quantity and distance of occult disease around the MRI-GTV.

Impact of pathological characteristics on local relapse after breast-conserving therapy: a subgroup analysis of the EORTC boost versus no boost trial.

Purpose: To investigate the long-term impact of pathologic characteristics and an extra boost dose of 16 Gy on local relapse, for stage I and II invasive breast cancer patients treated with breast conserving therapy (BCT).

Patients And Methods: In the European Organisation for Research and Treatment of Cancer boost versus no boost trial, after whole breast irradiation, patients with microscopically complete excision of invasive tumor, were randomly assigned to receive or not an extra boost dose of 16 Gy. For a subset of 1,616 patients central pathology review was performed.

Prediction of BRCA1-association in hereditary non-BRCA1/2 breast carcinomas with array-CGH.

Background: While new defects in BRCA1 are still being found, it is unclear whether current breast cancer diagnostics misses many BRCA1-associated cases. A reliable test that is able to indicate the involvement of BRCA1 deficiency in cancer genesis could support decision making in genetic counselling and clinical management. To find BRCA1-specific markers and explore the effectiveness of the current diagnostic strategy, we designed a classification method, validated it and examined whether we could find BRCA1-like breast tumours in a group of patients initially diagnosed as non-BRCA1/2 mutation carriers.

Adult pelvic sarcomas: a heterogeneous collection of sarcomas?

Introduction. Adult pelvic soft tissue sarcomas are a rare group of heterogeneous malignancies. These sarcomas differ from extremity and trunk soft tissue sarcomas in presentation, characteristics and response to treatment.

ATBF1 and NQO1 as candidate targets for allelic loss at chromosome arm 16q in breast cancer: absence of somatic ATBF1 mutations and no role for the C609T NQO1 polymorphism.

Background: Loss of heterozygosity (LOH) at chromosome arm 16q is frequently observed in human breast cancer, suggesting that one or more target tumor suppressor genes (TSGs) are located there. However, detailed mapping of the smallest region of LOH has not yet resulted in the identification of a TSG at 16q. Therefore, the present study attempted to identify TSGs using an approach based on mRNA expression.

Prognostic significance of macrophage infiltration in leiomyosarcomas.

Purpose: Macrophages are migratory cells that are frequently recruited to the site of tumors. Their presence is associated with poor clinical outcome in a variety of epithelial malignancies. The aim of this study is to examine the prognostic significance of tumor-associated macrophages in sarcomas.

Comparison of gene expression profiles predicting progression in breast cancer patients treated with tamoxifen.

Background: Molecular signatures that predict outcome in tamoxifen treated breast cancer patients have been identified. For the first time, we compared these response profiles in an independent cohort of (neo)adjuvant systemic treatment naïve breast cancer patients treated with first-line tamoxifen for metastatic disease.

Methods: From a consecutive series of 246 estrogen receptor (ER) positive primary tumors, gene expression profiling was performed on available frozen tumors using 44K oligoarrays (n = 69).

Use of 70-gene signature to predict prognosis of patients with node-negative breast cancer: a prospective community-based feasibility study (RASTER).

Background: A microarray-based 70-gene prognosis signature might improve the selection of patients with node-negative breast cancer for adjuvant systemic treatment. The main aims of this MicroarRAy PrognoSTics in Breast CancER (RASTER) study were to assess prospectively the feasibility of implementation of the 70-gene prognosis signature in community-based settings and its effect on adjuvant systemic treatment decisions when considered with treatment advice formulated from the Dutch Institute for Healthcare Improvement (CBO) and other guidelines.

Methods: Between January, 2004 and December, 2006, 812 women aged under 61 years with primary breast carcinoma (clinical T1-4N0M0) were enrolled.

Clinical outcome after selective treatment of patients diagnosed with ductal carcinoma in situ of the breast.

Background: The effect of treatment of patients diagnosed with ductal carcinoma in situ (DCIS) of the breast was evaluated, and factors associated with local recurrence were assessed.

Methods: The study involved 504 patients treated by means of wide local excision alone (WLE) (n = 91), wide local excision and radiotherapy (WLE+RT) (n = 119), or mastectomy (n = 294) at the Netherlands Cancer Institute between 1986 and 2005. Clinical, pathological, and follow-up data were evaluated.

Squamous cell carcinoma in situ of the breast: a light microscopic and immunohistochemical study of a previously undescribed lesion.

Three cases of squamous carcinoma in situ of the breast, one with an invasive component are described in women aged 35, 51, and 59 years. Two cases were detected by screening mammography. In 1 case, the squamous ductal carcinoma in situ was extensive.

Validation of clinical prediction rules for a low probability of nonsentinel and extensive lymph node involvement in breast cancer patients.

Background: Two recently developed clinical prediction rules aim to anticipate the lack of nonsentinel lymph node metastases and the involvement of less than 4 lymph nodes in breast cancer patients with positive sentinel lymph nodes (SLNs).

Methods: The University of Louisville Breast SLN Study clinical prediction rules were validated on an independent set of SLN-positive patients with tumors < or = 15 mm.

Results: The data on 475 and 473 patients, respectively, were used for the validation.

Somatic loss of BRCA1 and p53 in mice induces mammary tumors with features of human BRCA1-mutated basal-like breast cancer.

Women carrying germ-line mutations in BRCA1 are strongly predisposed to developing breast cancers with characteristic features also observed in sporadic basal-like breast cancers. They appear as high-grade tumors with high proliferation rates and pushing borders. On the molecular level, they are negative for hormone receptors and ERBB2, display frequent TP53 mutations, and express basal epithelial markers.

Sentinel lymph node biopsy and non-sentinel node involvement in special type breast carcinomas with a good prognosis.

This study aimed at identifying factors related to sentinel lymph node (SLN) involvement in patients with tubular, cribriform, mucinous or papillary breast carcinoma and those related to non-SLN metastases if an SLN was positive. Multivariate analyses involved logistic and stepwise regressions. The SLNs harboured metastases in 85 of 572 cases, 78 of whom underwent axillary dissection; 19 presented non-SLN positive disease.

Sentinel lymph node biopsy in staging small (up to 15 mm) breast carcinomas. Results from a European multi-institutional study.

Sentinel lymph node (SLN) biopsy has become the preferred method for the nodal staging of early breast cancer, but controversy exists regarding its universal use and consequences in small tumors. 2929 cases of breast carcinomas not larger than 15 mm and staged with SLN biopsy with or without axillary dissection were collected from the authors' institutions. The pathology of the SLNs included multilevel hematoxylin and eosin (HE) staining.

Breast cancer survival and tumor characteristics in premenopausal women carrying the CHEK2*1100delC germline mutation.

Purpose: Women carrying a CHEK2*1100delC germline mutation have an increased risk of developing breast cancer. This study aims to determine the proportion of CHEK2*1100delC carriers in a premenopausal breast cancer population, unselected for family history of breast cancer, and to investigate tumor characteristics and disease outcome with sufficient follow-up.

Patients And Methods: We identified a retrospective cohort of 1,479 patients, who received surgery for invasive breast cancer between 1970 and 1994.

Somatic inactivation of E-cadherin and p53 in mice leads to metastatic lobular mammary carcinoma through induction of anoikis resistance and angiogenesis.

Metastatic disease is the primary cause of death in breast cancer, the most common malignancy in Western women. Loss of E-cadherin is associated with tumor metastasis, as well as with invasive lobular carcinoma (ILC), which accounts for 10%-15% of all breast cancers. To study the role of E-cadherin in breast oncogenesis, we have introduced conditional E-cadherin mutations into a mouse tumor model based on epithelium-specific knockout of p53.

Classification of ductal carcinoma in situ by gene expression profiling.

Introduction: Ductal carcinoma in situ (DCIS) is characterised by the intraductal proliferation of malignant epithelial cells. Several histological classification systems have been developed, but assessing the histological type/grade of DCIS lesions is still challenging, making treatment decisions based on these features difficult. To obtain insight in the molecular basis of the development of different types of DCIS and its progression to invasive breast cancer, we have studied differences in gene expression between different types of DCIS and between DCIS and invasive breast carcinomas.

Ultrasonography and fine-needle aspiration cytology in the preoperative evaluation of melanoma patients eligible for sentinel node biopsy.

Background: Ultrasonography with fine-needle aspiration cytology (FNAC) has proven to be a valuable diagnostic tool in the preoperative workup of patients with breast cancer or penile cancer eligible for sentinel lymph node biopsy. The aim of this study was to evaluate the use of this technique in the initial assessment of patients with primary cutaneous melanoma.

Methods: A total of 107 patients with cutaneous melanoma eligible for sentinel node biopsy with clinically negative nodes were studied prospectively.

Additional axillary metastases and stage migration in breast cancer patients with micrometastases or submicrometastases in sentinel lymph nodes.

Background: In patients with breast cancer, micrometastases and submicrometastases are increasingly found in sentinel nodes when step sectioning and/or immunohistochemical staining are applied. The aims of the current study were to investigate the incidence of micro- and submicrometastases in the sentinel node, to estimate the risk of additional metastases in the remaining axillary lymph nodes, and to consider implications for staging and treatment.

Methods: A total of 2150 breast cancer patients who had undergone axillary sentinel node biopsy between 1999 and 2004 were retrospectively evaluated.

Breast-conserving treatment with or without radiotherapy in ductal carcinoma-in-situ: ten-year results of European Organisation for Research and Treatment of Cancer randomized phase III trial 10853--a study by the EORTC Breast Cancer Cooperative Group and EORTC Radiotherapy Group.

Purpose: The European Organisation for Research and Treatment of Cancer conducted a randomized trial investigating the role of radiotherapy (RT) after local excision (LE) of ductal carcinoma-in-situ (DCIS) of the breast. We analyzed the efficacy of RT with 10 years follow-up on both the overall risk of local recurrence (LR) and related to clinical, histologic, and treatment factors.

Patients And Methods: After complete LE, women with DCIS were randomly assigned to no further treatment or RT (50 Gy).

Ultrasonography and fine-needle aspiration cytology can spare breast cancer patients unnecessary sentinel lymph node biopsy.

Background: Some 30% to 40% of the breast cancer patients scheduled for sentinel node biopsy have axillary metastasis. Pilot studies suggest that ultrasonography is useful in the preoperative detection of such nodes. The aims of this study were to evaluate the sensitivity of preoperative ultrasonography and fine-needle aspiration cytology for detecting axillary metastases and to assess how often sentinel node biopsy could be avoided.

Contrast-enhanced MRI in breast cancer patients eligible for breast-conserving therapy: complementary value for subgroups of patients.

The aim of this study was to identify patients prior to breast-conserving therapy (BCT) who have complementary value of contrast-enhanced magnetic resonance imaging (MRI) over conventional imaging in the assessment of tumor extent. All patients were eligible for BCT according to conventional imaging, and underwent preoperative MRI as part of this study. One hundred and sixty-five patients (166 tumors) were included.

Lobular carcinoma of the breast with hybrid myoepithelial and secretory ("myosecretory") cell differentiation.

Three cases of lobular carcinoma of the breast showing a complex morphology that included myoepithelial cell differentiation are reported. One case was a pure in situ acinar lesion, while the other 2 cases were in situ and invasive carcinomas. Three different cell types were seen in these tumors: one was the phenotype commonly seen in the garden variety of in situ lobular carcinoma (LCIS) constituted by noncohesive round to ovoid cells with round nuclei and positivity for epithelial membrane antigen (EMA), estrogen receptor (ER), and progesteron receptor (PR).

Breast cancer metastasis: markers and models.

Breast cancer starts as a local disease, but it can metastasize to the lymph nodes and distant organs. At primary diagnosis, prognostic markers are used to assess whether the transition to systemic disease is likely to have occurred. The prevailing model of metastasis reflects this view--it suggests that metastatic capacity is a late, acquired event in tumorigenesis.

Additional breast lesions in patients eligible for breast-conserving therapy by MRI: impact on preoperative management and potential benefit of computerised analysis.

This study was conducted to assess the incidence and impact of additional findings from magnetic resonance imaging (MRI) on the workup of patients eligible for breast-conserving therapy (BCT) and to optimise the specificity of further workup by combining radiological reading with computerised analysis. One hundred and sixteen patients eligible for BCT underwent preoperative MRI where the gold standard was histology or follow-up (median 35 months, range 23-48). The incidence of additional findings and impact on treatment (wider excision/conversion to mastectomy) were assessed.