Comprehensive prognostic analysis in breast cancer integrating clinical, tumoral, micro-environmental and immunohistochemical criteria.

Significant morphological, clinical and biological prognostic factors vary according to molecular subtypes of breast tumors, yet comprehensive analysis of such factors linked to survival in each group is lacking. Clinicopathological and micro-environmental criteria, estrogen (ER), progesterone (PR) receptors, HER2, Ki67, basal markers, CD24, CD44, ALDH1, BCL2, E-Cadherin and Trio were assessed in 1070 primary operable breast cancers from a single center according to five main molecular subtypes and associations with distant metastasis-free survival (DMFS) were examined. There were 682 (64 %) luminal A (LA), 166 (16 %) Luminal B HER2 negative (LBH-), 47 (4 %) Luminal B HER2 positive (LBH+), 108 (10 %) triple negative (TN) and 67 (6 %) HER2-enriched tumors (H2+).

An array CGH based genomic instability index (G2I) is predictive of clinical outcome in breast cancer and reveals a subset of tumors without lymph node involvement but with poor prognosis.

Background: Despite entering complete remission after primary treatment, a substantial proportion of patients with early stage breast cancer will develop metastases. Prediction of such an outcome remains challenging despite the clinical use of several prognostic parameters. Several reports indicate that genomic instability, as reflected in specific chromosomal aneuploidies and variations in DNA content, influences clinical outcome but no precise definition of this parameter has yet been clearly established.

[Accuracy of intraoperative imprint cytology of sentinel lymph nodes in cT1 infiltrating breast cancer].

Intraoperative examination of sentinel lymph nodes (SLN) in breast cancer can avoid a new surgical procedure in case of positive SLN, but its value, efficacy and the methods used are still controversial. The aim of our study was to evaluate the imprint cytology intraoperative method of SLN analysis performed at our institution. We did a retrospective study of the sentinel lymph node procedures performed during a period of 24  months on cT1N0 unifocal breast cancers.

All atypia diagnosed at stereotactic vacuum-assisted breast biopsy do not need surgical excision.

The necessity of excision is debatable when atypia are diagnosed at stereotactic vacuum-assisted breast biopsy (microbiopsy). Among the 287 surgical excisions performed at Institut Bergonié from 1999 to 2009, we selected a case-control study group of 151 excisions; 52 involving all the diagnosed cancers and 99 randomly selected among the 235 excisions without cancer, following atypical microbiopsy (24 flat epithelial atypia; 50 atypical ductal hyperplasia; 14 lobular neoplasia; 63 mixed lesions). Mammographical calcification (type, extension, complete removal) and histological criteria of epithelial atypia (type, number of foci, size/extension), topography and microcalcification extension at microbiopsy were compared according to the presence or absence of cancer at excision.

Nucleic acid quality preservation by an alcohol-based fixative: comparison with frozen tumors in a routine pathology setting.

Pathologic diagnosis requires tissue fixation for histologic and immunohistologic analysis, and formalin is routinely used for this. The disadvantage of this fixative is its inability to preserve nucleic acids. Pathologic tumor diagnosis requires extensive molecular analyses, for which formalin fixation may be not adequate.

Ductal carcinoma in situ of the breast: influence of age on diagnostic, therapeutic, and prognostic features. Retrospective study of 812 patients.

Background: The objective of this retrospective study was to identify prognostic, diagnostic, and therapeutic disparities between younger (≤ 40 years) and older (> 40 years) women with ductal carcinoma in situ (DCIS) of the breast.

Methods: From 1971 to 2001, all patients treated for DCIS at Institut Bergonié were included in our analyses. Follow-up data was collected over 10 years.

Molecular apocrine differentiation is a common feature of breast cancer in patients with germline PTEN mutations.

Introduction: Breast carcinoma is the main malignant tumor occurring in patients with Cowden disease, a cancer-prone syndrome caused by germline mutation of the tumor suppressor gene PTEN characterized by the occurrence throughout life of hyperplastic, hamartomatous and malignant growths affecting various organs. The absence of known histological features for breast cancer arising in a PTEN-mutant background prompted us to explore them for potential new markers.

Methods: We first performed a microarray study of three tumors from patients with Cowden disease in the context of a transcriptomic study of 74 familial breast cancers.

Is it useful to detect lymphovascular invasion in lymph node-positive patients with primary operable breast cancer?

Background: Lymphovascular invasion (LVI) is a widely recognized prognostic factor in lymph node-negative breast cancers. However, there are only limited and controversial data about its prognostic significance in lymph node-positive patients.

Methods: Among 931 patients operated on and monitored at the authors' institution for an invasive breast carcinoma between 1989 and 1992, all 374 lymph node-positive breast cancers entered the study (median follow-up, 126 months).

[Adenoid cystic carcinoma of the breast: clinical, histological and immunohistochemical characterization].

Background: Adenoid cystic carcinoma (ACC) of the Breast is a rare tumour (less than 1 % of all breast carcinomas). The aim of this study was to determine the clinical, histological and immunohistochemical characteristics of these tumours.

Methods: From the database of the Bergonié Institute of Bordeaux, 30 cases of ACC were identified.

Prediction of HER2 gene status in Her2 2+ invasive breast cancer: a study of 108 cases comparing ASCO/CAP and FDA recommendations.

Most Her2 testing guidelines recommend that all cases scoring Her2 2+ by immunohistochemistry should be analyzed by fluorescent in situ hybridization (FISH) to determine HER2 status to confirm eligibility for Trastuzumab therapy in breast cancer. The aim of our study was to determine HER2 gene and chromosome 17 (CEN17) status in a series of 108 Her2 2+ consecutive cases and study the correlation between pathological characteristics of the tumors and HER2 amplification. Invasive breast cancers were tested by FISH using the Dako HER2 FISH pharmDx kit.

D2-40 in breast cancer: should we detect more vascular emboli?

Peritumoral emboli assessed on hematoxylin-eosin-stained slides are taken into account for treatment of patients with operable breast cancer. We assessed whether immunostaining with D2-40 improves the prognostic significance of emboli in a group of tumors with a large immunohistochemical sampling and a long-term follow-up. Topography, number, and extension of hematoxylin-eosin and D2-40 emboli were compared in 94 node-negative breast cancers (median number of immunostained slides per tumor: 3).

Distinction between isolated tumor cells and micrometastases in breast cancer: is it reliable and useful?

Background: In routine practice, the distinction between isolated tumor cells (ITC) and micrometastases (MIC) in patients with breast cancer is sometimes difficult to discern. The authors assessed differences in classifying patients according to the American Joint Commission on Cancer (AJCC) and the International Union Against Cancer (UICC) definitions and method of sizing.

Methods: We assessed the characteristics of metastatic deposits in only 1 involved lymph node in 337 patients with operable breast cancer (median follow-up, 15.

[Management of breast epithelial atypia].

While awaiting a molecular classification of breast epithelial atypia, the authors give some guidelines about their management, in reference to studies in literature and to their own experience at the Institut Bergonié. This experience is based on the analysis of 2,833 serially sectioned surgical breast biopsies performed for micro-calcifications without any palpable mass (median number of blocks per biopsy: 26) in patients with a long median follow-up (160 months). Some guidelines are given about the application of the WHO classification of atypical non invasive proliferative breast lesions, measurement of atypical ductal hyperplasia, management of patients with epithelial atypia on core needle biopsies and management of surgical biopsies corresponding to re excision to set out a small concomitant close cancer, present in nearly one third of the cases.

Epithelial atypia in biopsies performed for microcalcifications. practical considerations about 2,833 serially sectioned surgical biopsies with a long follow-up.

This study analyzes the occurrence of epithelial atypia in 2,833 serially sectioned surgical breast biopsies (SB) performed for microcalcifications (median number of blocks per SB:26) and the occurrence of subsequent cancer after an initial diagnosis of epithelial atypia (median follow-up 160 months). Epithelial atypia (flat epithelial atypia, atypical ductal hyperplasia, and lobular neoplasia) were found in 971 SB, with and without a concomitant cancer in 301 (31%) and 670 (69%) SB, respectively. Thus, isolated epithelial atypia were found in 670 out of the 2,833 SB (23%).

Identification of typical medullary breast carcinoma as a genomic sub-group of basal-like carcinomas, a heterogeneous new molecular entity.

Introduction: Typical medullary breast carcinoma (MBC) has recently been recognized to be part of the basal-like carcinoma spectrum, a feature in agreement with the high rate of TP53 mutations previously reported in MBCs. The present study was therefore designed to identify phenotypic and genetic alterations that distinguish MBCs from basal-like carcinomas (BLC).

Methods: Expression levels of estrogen receptor (ER), progesterone receptor (PR), ERBB2, TP53, cytokeratins (KRTs) 5/6, 14, 8/18, epidermal growth factor receptor and KIT, as well as TP53 gene sequence and high-density array comparative genomic hybridization (CGH) profiles, were assessed and compared in a series of 33 MBCs and 26 BLCs.

[Digitalized imaging pathology: application to quality control in cancer diagnosis].

Objectives: To test a double histology reading system based on digitalized imaging for cancer diagnosis.

Material And Methods: Pathology images of cancer diagnosis material were produced in real time by a digital imaging system integrated into the laboratory data processing system. Over a 30-day period, second readings were performed using the digitalized images.

Mammography of ductal carcinoma in situ of the breast: review of 909 cases with radiographic-pathologic correlations.

We retrospectively analysed mammographies of 909 ductal carcinoma in situ (DCIS) (1980-1999) and compared our results to those of literature. Microcalcifications were present in 75% of the cases, and soft-tissue abnormalities in 27% cases with association with calcifications in 14% of cases. Palpable masses were found in 12% of the cases and nipple discharge was present in 12% of the cases.

Immunohistochemically detected lymph node metastases from breast carcinoma: practical considerations about the new American Joint Committee on Cancer classification.

Background: The authors applied the sixth edition of the American Joint Committee on Cancer (AJCC) classification system to their previously published group of patients with breast carcinoma who had immunohistochemically detected lymph node metastases.

Methods: The original lymph node-negative slides from 218 patients, including 129 patients with infiltrating duct carcinoma (IDC) and 89 patients with infiltrating lobular carcinoma (ILC), were reviewed and then destained to perform immunohistochemistry. Each tumor cell deposit was measured.

[Diagnostic approach to breast papillary lesions].

Breast papillary lesions are difficult to interpret and include a large variety of benign, atypical and malignant lesions. We report the case of a 41-Year-old woman presenting with an intracystic papillary carcinoma, in order to illustrate our pragmatic diagnostic approach, which includes the use of a decision tree, useful for differentiating the different types of breast papillary lesions.

[Strategies for management of axillary lymph nodes in breast cancer. Point of view of the Institut Bergonié. ].

Sentinel lymph node biopsy in breast cancer has changed pathology management of axillary lymph nodes by pathologists, but there is still no consensus either for serial sectioning nor for immunohistochemistry. We analyze: 1) data in the literature about the prognostic significance of micrometastases (pNlmi) and immunohistochemically detected infiltrating tumor cells (pN0(i+) in axillary lymph nodes. 2) management strategies at the Bergonié Institute and by other teams for axillary lymph nodes and sentinel lymph nodes.

Breast ductal carcinoma in situ with microinvasion: a definition supported by a long-term study of 1248 serially sectioned ductal carcinomas.

Background: The significance of microinvasion is still debated and clinical management is controversial. The authors defined ductal carcinoma in situ with microinvasion (DCIS-MI) as DCIS with infiltration of the periductal stroma by a few tumor cells, singly (type 1) or in clusters (type 2). With this definition, the authors attempted to evaluate the clinical significance of microinvasion.