Quantitative comparison of immunohistochemical HER2-low detection in an interlaboratory study.

Aims: Recently, human epidermal growth factor 2 (HER2)-low (i.e. HER2 score 1+ or 2+ without amplification) breast cancer patients became eligible for trastuzumab-deruxtecan treatment.

Estrogen regulation and functional role of FGFR4 in estrogen receptor positive breast cancer.

Background: Resistance to endocrine therapy is a major challenge of managing estrogen receptor positive (ER+) breast cancer. We previously reported frequent overexpression of FGFR4 in endocrine resistant cell lines and breast cancers that recurred and metastasized following endocrine therapy, suggesting FGFR4 as a potential driver of endocrine resistance. In this study, we investigated the role of FGFR4 in mediating endocrine resistance and explored the therapeutic potential of targeting FGFR4 in advanced breast cancer.

Analytical validation of the 7-gene biosignature for prediction of recurrence risk and radiation therapy benefit for breast ductal carcinoma .

Purpose: Ductal carcinoma (DCIS), is a noninvasive breast cancer, representing 20-25% of breast cancer diagnoses in the USA. Current treatment options for DCIS include mastectomy or breast-conserving surgery (BCS) with or without radiation therapy (RT), but optimal risk-adjusted treatment selection remains a challenge. Findings from past and recent clinical trials have failed to identify a 'low risk' group of patients who do not benefit significantly from RT after BCS.

Novel markers in breast pathology.

Breast pathology is an ever-expanding database of information which includes markers, or biomarkers, that detect or help treat the disease as prognostic or predictive information. This review focuses on these aspects of biomarkers which are grounded in immunohistochemistry, liquid biopsies and next-generation sequencing.

Deep learning models for histologic grading of breast cancer and association with disease prognosis.

Histologic grading of breast cancer involves review and scoring of three well-established morphologic features: mitotic count, nuclear pleomorphism, and tubule formation. Taken together, these features form the basis of the Nottingham Grading System which is used to inform breast cancer characterization and prognosis. In this study, we develop deep learning models to perform histologic scoring of all three components using digitized hematoxylin and eosin-stained slides containing invasive breast carcinoma.

The Story of the Magee Equations: The Ultimate in Applied Immunohistochemistry.

Magee equations (MEs) are a set of multivariable models that were developed to estimate the actual Onco type DX (ODX) recurrence score in invasive breast cancer. The equations were derived from standard histopathologic factors and semiquantitative immunohistochemical scores of routinely used biomarkers. The 3 equations use slightly different parameters but provide similar results.

A Novel Biosignature Identifies Patients With DCIS With High Risk of Local Recurrence After Breast Conserving Surgery and Radiation Therapy.

Purpose: There is an unmet need to identify women diagnosed with ductal carcinoma in situ (DCIS) with a low risk of in-breast recurrence (IBR) after breast conserving surgery (BCS), which could omit radiation therapy (RT), and also to identify those with elevated IBR risk remaining after BCS plus RT. We evaluated a novel biosignature for a residual risk subtype (RRt) to help identify patients with elevated IBR risk after BCS plus RT.

Methods And Materials: Women with DCIS treated with BCS with or without RT at centers in the US, Australia, and Sweden (n = 926) were evaluated.

A Consortium for Analytic Standardization in Immunohistochemistry.

Context.—: The authors announce the launch of the Consortium for Analytic Standardization in Immunohistochemistry, funded with a grant from the National Cancer Institute. As with other laboratory testing, analytic standards are important for many different stakeholders: commercial vendors of instruments and reagents, biopharmaceutical firms, pathologists, scientists, clinical laboratories, external quality assurance organizations, and regulatory bodies.

Determining breast cancer biomarker status and associated morphological features using deep learning.

Background: Breast cancer management depends on biomarkers including estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (ER/PR/HER2). Though existing scoring systems are widely used and well-validated, they can involve costly preparation and variable interpretation. Additionally, discordances between histology and expected biomarker findings can prompt repeat testing to address biological, interpretative, or technical reasons for unexpected results.

Avoiding "False Positive" and "False Negative" Immunohistochemical Results in Breast Pathology.

Immunohistochemistry (IHC) plays an important role in the evaluation of breast pathology specimens to provide both diagnostic and prognostic/therapeutic information. Although most IHCs used in breast pathology can be easily interpreted, pitfalls do exist, especially in some uncommon scenarios. This review intends to focus on the challenging areas such as the interpretation of myoepithelial cell markers in differentiating benign proliferation and in situ carcinoma from invasive carcinoma, lobular cell markers in differentiating lobular from ductal carcinoma, cytokeratin and other markers in diagnosing metaplastic carcinoma, and breast tissue origin markers in diagnosing breast primary carcinoma.

Prognostic Utility of Breast Cancer Index to Stratify Distant Recurrence Risk in Invasive Lobular Carcinoma.

Purpose: The prognostic utility of Breast Cancer Index (BCI) for risk assessment of overall (0-10 years), early (0-5 years), and late (5-10 years) distant recurrence (DR) in hormone receptor-positive (HR+) invasive lobular carcinoma (ILC) was evaluated.

Experimental Design: BCI gene expression analysis was performed blinded to clinical outcome utilizing tumor specimens from patients with HR+ ILC from a multi-institutional cohort. The primary endpoint was time to DR.

Metaplastic carcinomas of the breast without evidence of epithelial differentiation: a diagnostic approach for management.

Aims: Although rare, malignant sarcomatoid breast tumours without evidence of epithelial differentiation comprise a diagnostic challenge with management implications. Earlier studies have generally considered these to be primary breast sarcomas; however, supporting evidence is lacking and management remains variable. This study aimed to provide an evidence-based approach to improve the consistency of diagnosis and management for such cases.

Best Practice (Efficient) Immunohistologic Panel for Diagnosing Metaplastic Breast Carcinoma.

Immunohistochemistry (IHC) plays a key role in the diagnosis of metaplastic breast carcinomas (MBCs), particularly the spindle cell variant. The most efficient immunopanel has yet to be developed. We studied the immunoprofile of 45 MBCs including 23 matrix-producing MBCs, 11 squamous cell carcinomas, 6 spindle cell carcinomas, and 5 mixed-subtypes (2 cases including spindle cell components).

Prosigna® breast cancer assay: histopathologic correlation, development, and assessment of size, nodal status, Ki-67 (SiNK™) index for breast cancer prognosis.

The Prosigna® assay is a United States Food and Drug Administration (US-FDA) cleared molecular test for prognostic use in hormone receptor-positive stage I/II breast cancer in postmenopausal women. We analyzed histopathologic features of 79 cases with Prosigna® assay results and found a significant correlation between tumor size, grade, and Ki-67 labeling index with Prosigna® score (0-40, 41-60, and 61-100) and Prosigna® risk categories. Since the Prosigna® risk stratification is influenced by lymph node status, we designed an index that included lymph node status and the two most correlated variables (size and Ki-67 labeling index).

Differential Regulation and Targeting of Estrogen Receptor α Turnover in Invasive Lobular Breast Carcinoma.

Invasive lobular breast carcinoma (ILC) accounts for 10% to 15% of breast cancers diagnosed annually. Evidence suggests that some aspects of endocrine treatment response might differ between invasive ductal carcinoma (IDC) and ILC, and that patients with ILC have worse long-term survival. We analyzed The Cancer Genome Atlas dataset and observed lower levels of ESR1 mRNA (P = 0.

The healthcare value of the Magee Decision Algorithm™: use of Magee Equations™ and mitosis score to safely forgo molecular testing in breast cancer.

Magee Equations™ are multivariable models that can estimate oncotype DX® Recurrence Score, and Magee Equation 3 has been shown to have chemopredictive value in the neoadjuvant setting as a standalone test. The current study tests the accuracy of Magee Decision Algorithm™ using a large in-house database. According to the algorithm, if all Magee Equation scores are <18, or 18-25 with a mitosis score of 1, then oncotype testing is not required as the actual oncotype recurrence score is expected to be ≤25 (labeled "do not send").

Immunohistochemical Markers With Potential Diagnostic, Prognostic, and Therapeutic Significance in Uterine Carcinosarcoma: A Clinicopathologic Study of 43 Cases.

Uterine carcinosarcomas (UCS) are rare and highly aggressive tumors. Although it is currently accepted that the majority of UCS are metaplastic carcinomas, their aggressive behavior is unparalleled to that of any other high-grade endometrial neoplasms. Therefore, the search for the distinct immunohistochemical and molecular features that could help in the development of new treatment strategies continues.

Patient characteristics associated with being offered take home naloxone in a busy, urban emergency department: a retrospective chart review.

Background: Overdose deaths can be prevented by distributing take home naloxone (THN) kits. The emergency department (ED) is an opportune setting for overdose prevention, as people who use opioids frequently present for emergency care, and those who have overdosed are at high risk for future overdose death. We evaluated the implementation of an ED-based THN program by measuring the extent to which THN was offered to patients presenting with opioid overdose.

Frequent amplifications of ESR1, ERBB2 and MDM4 in primary invasive lobular breast carcinoma.

Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer following invasive ductal carcinoma (IDC). To identify potential genetic drivers of ILC progression, we used NanoString nCounter technology to investigate the DNA copy number (CN) in 70 well-curated primary ILC samples. We confirmed prior observations of frequent amplification of CCND1 (33%), and MYC (17%) in ILC, but additionally identified a substantial subset of ILCs with ESR1 and ERBB2 (19%) amplifications.

Follow-up outcomes of benign vascular lesions of breast diagnosed on core needle biopsy: A study of 117 cases.

Benign vascular lesions of breast are uncommon findings on core biopsy and surgical excision has been recommended to rule out a more serious lesion. However, a recent study suggested that excision may be spared for vascular lesion without atypia. The aim of this study was to assess the follow-up outcomes in lesions yielding benign vascular lesions on core biopsy.

Isolated Flat Epithelial Atypia on Core Biopsy Specimens Is Associated With a Low Risk of Upgrade at Excision.

Objectives: We present a retrospective review of 111 breast core biopsy specimens with flat epithelial atypia (FEA) and corresponding excision to better understand rates of upgrade following this diagnosis.

Methods: In total, 252 breast core biopsy specimens were identified. Cases were excluded if biopsy slides or excision results were unavailable, for ipsilateral carcinoma or other findings warranting excision, or biopsy performed for indications other than mammographically detected calcifications.