Lobular Carcinoma in Situ: A 29-Year Longitudinal Experience Evaluating Clinicopathologic Features and Breast Cancer Risk.

Purpose: The increased breast cancer risk conferred by a diagnosis of lobular carcinoma in situ (LCIS) is poorly understood. Here, we review our 29-year longitudinal experience with LCIS to evaluate factors associated with breast cancer risk.

Patients And Methods: Patients participating in surveillance after an LCIS diagnosis are observed in a prospectively maintained database.

Gene expression profiling of lobular carcinoma in situ reveals candidate precursor genes for invasion.

Purpose: Lobular carcinoma in situ (LCIS) is both a risk indicator and non-obligate precursor of invasive lobular carcinoma (ILC). We sought to characterize the transcriptomic features of LCIS and ILC, with a focus on the identification of intrinsic molecular subtypes of LCIS and the changes involved in the progression from normal breast epithelium to LCIS and ILC.

Methods: Fresh-frozen classic LCIS, classic ILC, and normal breast epithelium (N) from women undergoing prophylactic or therapeutic mastectomy were prospectively collected, laser-capture microdissected, and subjected to gene expression profiling using Affymetrix HG-U133A 2.

Is there a role for routine screening MRI in women with LCIS?

Women with lobular carcinoma in situ (LCIS) have an elevated breast cancer risk, yet the benefit of MRI screening is unclear. We examined cancer detection rates with mammography alone versus mammography plus MRI in this high-risk population. From a prospectively maintained, single-institution database, we identified 776 patients diagnosed with LCIS after the adoption of screening MRI in April 1999.

Clonal relatedness between lobular carcinoma in situ and synchronous malignant lesions.

Introduction: Lobular carcinoma in situ (LCIS) has been accepted as a marker of risk for the development of invasive breast cancer, yet modern models of breast carcinogenesis include LCIS as a precursor of low-grade carcinomas. We provide evidence favoring a clonal origin for LCIS and synchronous estrogen receptor-positive malignant lesions of the ductal and lobular phenotype.

Methods: Patients with prior LCIS undergoing mastectomy were identified preoperatively from 2003 to 2008.

Cadherin-catenin complex dissociation in lobular neoplasia of the breast.

E-cadherin (E-CD) inactivation with loss of E-CD-mediated cell adhesion is the hallmark of lesions of the lobular phenotype. E-CD is typically absent by immunohistochemistry in both lobular carcinoma in situ (LCIS) and invasive lobular lesions, suggesting it occurs early in the neoplastic process. In laboratory models, downstream post-transcriptional modifiers such as TWIST and SNAIL contribute to the dissociation of the intracellular component of the cadherin-catenin complex (CCC), resulting in tumor progression and invasion.

Differentially expressed genes in window trials are influenced by the wound-healing process: lessons learned from a pilot study with anastrozole.

Background: Perioperative window trials provide an opportunity to obtain intact tumor samples at two different time-points for evaluation of potential surrogate biomarkers. We report results of a pilot trial designed to determine if treatment-mediated changes in gene expression can be detected in formalin-fixed paraffin-embedded (FFPE) samples after 10-d exposure to anastrozole in estrogen receptor (ER)-positive breast cancer compared with untreated controls.

Methods: Paired tumor samples (biopsy, surgical) were obtained from 26 postmenopausal women with ER-positive breast cancer.

A prospective evaluation of the durability of palliative interventions for patients with metastatic breast cancer.

Background: Although systemic therapy for metastatic breast cancer (MBC) continues to evolve, there are scant data to guide physicians and patients when symptoms develop. In this article, the authors report the frequency and durability of palliative procedures performed in the setting of MBC.

Methods: From July 2002 to June 2003, 91 patients with MBC underwent 109 palliative procedures (operative, n=76; IR n=39, endoscopic n=3).

Protocol for PTEN expression by immunohistochemistry in formalin-fixed paraffin-embedded human breast carcinoma.

The PI3K/PTEN pathway plays a major role in carcinogenesis. Dysregulation of this pathway occurs frequently in breast cancer, and loss of PTEN expression is emerging as a potentially important mechanism of resistance to the widely used anti-HER2 therapy, trastuzumab. However, assays for loss of PTEN expression have suffered from lack of consistency.

Stage IV breast cancer in the era of targeted therapy: does surgery of the primary tumor matter?

Background: Multiple studies have suggested that resection of the primary tumor improves survival in patients with stage IV breast cancer, yet in the era of targeted therapy, the relation between surgery and tumor molecular subtype is unknown. The objective of the current study was to identify subsets of patients who may benefit from primary tumor treatment and assess the frequency of local disease progression.

Methods: Patients presenting with stage IV breast cancer and intact primary tumors (n = 186) were identified from a prospectively maintained clinical database (2000-2004) and clinical data were abstracted (grading determined according to the American Joint Committee on Cancer staging system).

Lessons learned from 416 cases of nipple discharge of the breast.

Background: For patients with nipple discharge (ND), surgical duct excision is often required to exclude underlying malignancy. Our objective was to define clinical predictors of malignancy and examine the utility of common preoperative studies.

Study Design: We retrospectively identified 475 patients presenting with a chief complaint of ND from 1995 to 2005; 416 (88%) were eligible for review.

The significance of nipple discharge of the male breast.

Although male breast cancer typically presents as a palpable mass, failure to recognize the significance of other symptoms may lead to a delay in diagnosis. Here we present our experience with male patients presenting with a chief complaint of nipple discharge (ND). Using the ICD-9 code for "breast symptoms," we identified 2,319 patients without a current cancer diagnosis who presented to Memorial Sloan-Kettering Cancer Center for evaluation; 24 (1%) patients were male (1995-2005).

Changing indications for surgery in patients with stage IV breast cancer: a current perspective.

Background: Evolving concepts of cancer biology and emerging evidence of a potential survival benefit from local surgery have raised the question of an expanded role for surgery in select patients with metastatic breast cancer (MBC). To determine whether such developments have influenced clinical practice, the authors evaluated surgical practice patterns in the study institution over the last 15 years.

Methods: Two institutional databases were screened to identify patients with MBC who underwent breast surgery (1990-2005).

MRI identifies otherwise occult disease in select patients with Paget disease of the nipple.

Introduction: For patients with Paget disease (PD) of the nipple, preoperative imaging to detect and evaluate the extent of an underlying malignancy can facilitate appropriate treatment planning. The purpose of this study was to evaluate the role of breast MRI in this setting.

Study Design: Using ICD-9 codes for "breast symptoms," we identified 2,294 patients without a current cancer diagnosis seen at our institution (1995 to 2006).

The predictive value of ductography and magnetic resonance imaging in the management of nipple discharge.

Background: Standard evaluation (physical examination, mammography, sonography) often fails to identify an underlying lesion in patients with suspicious nipple discharge. The aim of this study was to determine the predictive value of ductography (DG) and magnetic resonance imaging (MRI) in this setting.

Methods: Using ICD-9 codes, we retrospectively identified 376 patients who presented with suspicious nipple discharge (ND) (1995-2005); 306 patients (68%) had negative standard evaluation.