Pilot Study on the Utility of Circulating HER2/Neu Levels in the Serum of Breast Cancer Patients.

Background/aim: Accurate and timely assessment of the human epidermal growth factor receptor 2 (HER2/neu) overexpression is pivotal for the identification of breast cancer (BC) patients that could benefit from HER2-targeted therapy. Currently approved tissue-based HER2 assays (tHER2) are limited to testing HER2 status on tumor samples obtained at a few points in time during the course of the disease. Herein, we assessed serum HER2 (sHER2) status longitudinally in 81 serial samples prospectively collected from 43 consenting patients pre- and post-therapy to revisit the idea of serum testing in the follow-up of BC patients.

Intraoperative Assessment of Sentinel Lymph Nodes in Breast Cancer Patients Post-Neoadjuvant Therapy.

Background: Shift toward minimizing axillary lymph node dissection in patients with breast cancer post neoadjuvant therapy has led to the assessment of sentinel lymph nodes by frozen section intraoperatively to determine the need for axillary lymph node dissection. However, few studies have examined the accuracy of sentinel lymph node frozen section after neoadjuvant therapy. Our objective is to compare the accuracy of sentinel lymph node frozen section in patients with breast cancer with and without neoadjuvant therapy and to identify features that may influence accuracy.

Ductal carcinoma in situ of the breast: an update for the pathologist in the era of individualized risk assessment and tailored therapies.

Ductal carcinoma in situ (DCIS) is a neoplastic proliferation of mammary ductal epithelial cells confined to the ductal-lobular system, and a non-obligate precursor of invasive disease. While there has been a significant increase in the diagnosis of DCIS in recent years due to uptake of mammography screening, there has been little change in the rate of invasive recurrence, indicating that a large proportion of patients diagnosed with DCIS will never develop invasive disease. The main issue for clinicians is how to reliably predict the prognosis of DCIS in order to individualize patient treatment, especially as treatment ranges from surveillance only, breast-conserving surgery only, to breast-conserving surgery plus radiotherapy and/or hormonal therapy, and mastectomy with or without radiotherapy.

Comparative Analysis of Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer According to 2007 and 2013 American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations.

Purpose To study the effect of the 2013 updates to the 2007 American Society of Clinical Oncology/College of American Pathologists recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer on testing patterns and interpretation in a large regional reference laboratory. Patients and Methods Patient cases with HER2 testing scores for breast biomarker evaluation were selected from our laboratory information system during two 12-month periods (2012 and 2014). The number of tests performed, type of specimens, proportion of HER2-positive and equivocal patient cases, and number of repeat tests on subsequent excisional specimens were examined and compared.

Human epidermal growth factor receptor 2 testing in primary breast cancer in the era of standardized testing: a Canadian prospective study.

Purpose: Therapies that target overexpression of human epidermal growth factor receptor 2 (HER2) rely on accurate and timely assessment of all patients with new diagnoses. This study examines HER2 testing of primary breast cancer tissue when performed with immunohistochemistry (IHC) and additional in situ hybridization (ISH) for negative cases (IHC 0/1+). The analysis focuses on the rate of false-negative HER2 tests, defined as IHC 0/1+ with an ISH ratio ≥ 2.

HER2 in situ hybridization in breast cancer: clinical implications of polysomy 17 and genetic heterogeneity.

Trastuzumab-containing therapy is a standard of care for patients with HER2+ breast cancer. HER2 status is routinely assigned using in situ hybridization to assess HER2 gene amplification, but interpretation of in situ hybridization results may be challenging in tumors with chromosome 17 polysomy or intratumoral genetic heterogeneity. Apparent chromosome 17 polysomy, defined by increased chromosome enumeration probe 17 (CEP17) signal number, is a common genetic aberration in breast cancer and represents an alternative mechanism for increasing HER2 copy number.

Experts' opinion: Recommendations for retesting breast cancer metastases for HER2 and hormone receptor status.

The human epidermal growth factor receptor 2 (HER2) and hormone receptor status of recurrent breast cancer may change between the tumor and metastases from negative to positive and vice versa, potentially affecting the treatment regimen. Retesting of metastases may therefore be crucial to allow appropriate selection of patients for whom targeted therapy is indicated; however, retesting is not routinely performed. This article recommends that metastases be retested for HER2 and hormone receptor status and provides practical guidance on when and how to retest, as agreed by a panel of expert pathologists with extensive experience of HER2 and hormone receptor testing.

Systematic review on hormone receptor testing in breast cancer.

Assessment of hormone receptors (estrogen and progesterone) helps to direct therapy for women with breast cancer. Immunohistochemistry is most commonly used to assess hormone receptor status and it is essential that these tests are performed accurately and reliably within and across laboratories. The overall purpose of this guideline is to improve the quality and accuracy of hormone receptor testing and its utility as a prognostic and predictive marker for invasive and in situ breast cancer.

Time to disease recurrence in basal-type breast cancers: effects of tumor size and lymph node status.

Background: : Basal-like breast cancers are a subgroup of breast cancers defined by the absence of staining for estrogen-receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2/neu) and by positive staining for the cytokeratins (CKs) expressed in the myoepithelial cells of the ducts and lobules (CK5/CK6, CK14) and for epidermal growth factor receptor (EGFR). This class of tumors has an unusually aggressive course, and it is not clear whether conventional prognostic factors for breast cancers also predict outcome for patients who have the basal phenotype.

Methods: : A panel of 962 breast cancers was stained for 5 markers (ER, PR, HER-2/neu, CK5/CK6, and EGFR).

Value and limitations of measuring HER-2 extracellular domain in the serum of breast cancer patients.

The human epidermal receptor-2 (HER-2) is overexpressed or amplified in 15% to 25% of breast cancers. Determination of HER-2 tumor status offers clinically useful information, as it selects patients who may benefit from treatment with trastuzumab, the monoclonal antibody against HER-2. Currently approved methods for HER-2 testing include immunohistochemistry or fluorescent in situ hybridization using tumor tissue.

Intraoperative consultation for axillary sentinel lymph node biopsy: an 8-year audit.

To summarize the authors' 8-year institutional experience with intraoperative consultation via frozen section (FS) on sentinel lymph node biopsy (SLNB) in breast cancer patients we recorded the, complete operative procedure including additional surgery on the ipsilateral axilla and intraoperative consultation and permanent histopathologic processing for all cases with inoperative consultation on SLNB in breast cancer patients between the groups, chi(2) and Fisher's exact tests were used. Intraoperative consultation was positive in 116/706 cases (16.4%) and final pathology in 158/706 cases (22.

Patterns of recurrence in the basal and non-basal subtypes of triple-negative breast cancers.

Traditional prognostic markers for breast cancer include estrogen receptor (ER), progesterone receptor (ER) and HER2/neu. Negative staining for these three markers defines the 'triple-negative' phenotype. By adding markers for cytokeratin 5/6 and EGFR, triple-negative breast cancers can be divided into 'basal-like' and 'normal-like' subgroups.

Immunophenotyping of serous carcinoma of the female genital tract.

To update the data on the expression of 'mesothelioma markers' by serous carcinomas of various sites we have studied cases from ovary (n=56), endometrium (n=37), fallopian tube (n=6), primary peritoneum (n=5) and cervix (n=3) using a panel of antibodies (WT1, P53, estrogen receptors, HER2/neu, D2-40, cytokeratin 5/6 and E-cadherin). Ovarian carcinomas demonstrated D2-40 and cytokeratin 5/6 immunoreactivity in 23.2 and 55.

Pattern of metastatic spread in triple-negative breast cancer.

Purpose: The prognosis of women with triple-negative breast cancers (defined as cancers that are estrogen receptor-negative, progesterone receptor-negative and HER2/neu negative) is poor, compared to women with other subtypes of breast cancer. It is proposed that the underlying difference in recurrence rates may be explained in part by different routes of metastatic spread.

Experimental Design: We studied a cohort of 1608 patients diagnosed with breast cancer, diagnosed between January 1987 and December 1997 at Women's College Hospital in Toronto.

Expression of c-kit in fibroepithelial lesions of the breast is a mast cell phenomenon.

The expression of c-kit, a protooncogene tyrosine kinase receptor (CD117), in phyllodes tumors of the breast has been the subject of recent investigations. We examined stromal c-kit expression by immunohistochemistry in 68 cases comprising fibroadenomas, fibroadenomas with cellular stroma, and benign, borderline, and malignant phyllodes tumors. Membrane staining was identified in the epithelium of 82% of cases, representing all diagnostic categories in the study.

Estrogen and progesterone receptor levels in nonneoplastic breast epithelium of breast cancer cases versus benign breast biopsy controls.

Background: Previous studies and biological mechanisms of carcinogenesis suggest that the steroid receptor content of benign breast epithelium may be related to breast cancer risk. The objective in this study was to compare the levels of estrogen receptor-alpha (ER) and progesterone receptor (PR) in nonneoplastic breast epithelium between breast cancer cases and biopsy controls.

Methods: Between 1995 and 1997 at two sites (Women's College Hospital in Toronto and Kingston General Hospital), 667 women who were scheduled for diagnostic excisional breast biopsies completed a questionnaire providing personal information and agreed to allow analysis of routinely resected tissue.

Triple-negative breast cancer: clinical features and patterns of recurrence.

Purpose: To compare the clinical features, natural history, and outcomes for women with "triple-negative" breast cancer with women with other types of breast cancer.

Experimental Design: We studied a cohort of 1,601 patients with breast cancer, diagnosed between January 1987 and December 1997 at Women's College Hospital in Toronto. Triple-negative breast cancers were defined as those that were estrogen receptor negative, progesterone receptor negative, and HER2neu negative.

Standardization of HER2 testing: results of an international proficiency-testing ring study.

Human epidermal growth factor receptor 2 (HER2) positivity in breast cancer is a prognostic factor regarding tumor aggressiveness and a predictive factor for response to trastuzumab (Herceptin). Early and accurate HER2 testing of all breast cancer patients at primary diagnosis is essential for optimal disease management. Routine HER2 tests, such as immunohistochemistry and fluorescence in situ hybridization (FISH), are subject to interlaboratory variation, and validation by laboratory proficiency testing is important to improve standardization.

American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer.

Purpose: To develop a guideline to improve the accuracy of human epidermal growth factor receptor 2(HER2) testing in invasive breast cancer and its utility as a predictive marker.

Methods: The American Society of Clinical Oncology and the College of American Pathologists convened an expert panel, which conducted a systematic review of the literature and developed recommendations for optimal HER2 testing performance. The guideline was reviewed by selected experts and approved by the board of directors for both organizations.

American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer.

Purpose: To develop a guideline to improve the accuracy of human epidermal growth factor receptor 2 (HER2) testing in invasive breast cancer and its utility as a predictive marker.

Methods: The American Society of Clinical Oncology and the College of American Pathologists convened an expert panel, which conducted a systematic review of the literature and developed recommendations for optimal HER2 testing performance. The guideline was reviewed by selected experts and approved by the board of directors for both organizations.

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.

Chromogenic in-situ hybridization: a viable alternative to fluorescence in-situ hybridization in the HER2 testing algorithm.

Assessment of human epidermal growth factor receptor-2 status is standard practice in women with breast cancer. Most laboratories use immunohistochemistry as a screening test, with equivocal results confirmed by fluorescence in-situ hybridization (FISH). Chromogenic in-situ hybridization (CISH) is a relatively new method for detection of gene amplification using a peroxidase reaction, which can be viewed using a standard light microscope.

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.