A Comparative Analysis of the Value of HER2 Immunohistochemistry Scoring in Primary and Metastatic Breast Cancer, in the Era of HER2 "Low" Breast Cancers.

Background: In the DESTINY-B04 trial, patients with pretreated HER2 low metastatic breast cancer (defined as immunohistochemistry score of 1+ or 2+ and negative in situ hybridization) had significant survival improvement with Trastuzumab therapy.

Methods: The goal of our study was to compare the HER2 immunohistochemistry scores of paired primary and metastatic breast cancer, with emphasis on HER2 low criteria and its implications for detailed immunohistochemistry interpretation. Using the pathology database from 2011, we identified 272 cases of primary breast cancers with paired metastases.

Best practices for achieving consensus in HER2-low expression in breast cancer: current perspectives from practising pathologists.

Aims: Human epidermal growth factor receptor 2 (HER2) expression is an important biomarker in breast cancer (BC). Most BC cases categorised as HER2-negative (HER2-) express low levels of HER2 [immunohistochemistry (IHC) 1+ or IHC 2+/in-situ hybridisation not amplified (ISH-)] and represent a clinically relevant therapeutic category that is amenable to targeted therapy using a recently approved HER2-directed antibody-drug conjugate. A group of practising pathologists, with expertise in breast pathology and BC biomarker testing, outline best practices and guidance for achieving consensus in HER2 IHC scoring for BC.

Identification of Glandular (Acinar)/Tubule Formation in Invasive Carcinoma of the Breast: A Study to Determine Concordance Using the World Health Organization Definition.

Context.—: The Nottingham Grading System (NGS) developed by Elston and Ellis is used to grade invasive breast cancer (IBC). Glandular (acinar)/tubule formation is a component of NGS.

Analytical Validation of the PreciseDx Digital Prognostic Breast Cancer Test in Early-Stage Breast Cancer.

Background: PreciseDx Breast (PDxBr) is a digital test that predicts early-stage breast cancer recurrence within 6-years of diagnosis.

Materials And Methods: Using hematoxylin and eosin-stained whole slide images of invasive breast cancer (IBC) and artificial intelligence-enabled morphology feature array, microanatomic features are generated. Morphometric attributes in combination with patient's age, tumor size, stage, and lymph node status predict disease free survival using a proprietary algorithm.

Emerging Landscape of Targeted Therapy of Breast Cancers With Low Human Epidermal Growth Factor Receptor 2 Protein Expression.

Context.—: Human epidermal growth factor receptor 2 (HER2) status in breast cancer is currently classified as negative or positive for selecting patients for anti-HER2 targeted therapy. The evolution of the HER2 status has included a new HER2-low category defined as an HER2 immunohistochemistry score of 1+ or 2+ without gene amplification.

Correlation of the Ki67 Working Group prognostic risk categories with the Oncotype DX Recurrence Score in early breast cancer.

Background: The relationship between Ki67 assessed by immunohistochemistry (IHC) and the Oncotype DX Recurrence Score (RS) is unclear. The objective of this study was to determine the correlation between the 21-gene RS and IHC-measured Ki67 with the prognostic classification groups recommended by the International Ki67 Working Group (IKWG).

Methods: The authors performed a retrospective chart review of women who had hormone receptor (HR)-positive, human epidermal growth factor receptor 2-negative early breast cancer with zero to three positive lymph nodes and both Ki67 and the 21-gene RS performed at their institution from 2013 to 2021.

Concordance in Breast Cancer Grading by Artificial Intelligence on Whole Slide Images Compares With a Multi-Institutional Cohort of Breast Pathologists.

Context.—: Breast carcinoma grade, as determined by the Nottingham Grading System (NGS), is an important criterion for determining prognosis. The NGS is based on 3 parameters: tubule formation (TF), nuclear pleomorphism (NP), and mitotic count (MC).

Mastectomy or Margin Re-excision? A Nomogram for Close/Positive Margins After Lumpectomy for DCIS.

Background: Anatomic extent of ductal carcinoma in situ (DCIS) may be uncertain in spite of clinical, pathologic, and imaging data. Consequently close/positive margins are common with lumpectomy for DCIS and often lead to a challenge in deciding whether to perform a re-excision or mastectomy.

Patients And Methods: From a single health system, we identified cases of lumpectomy for DCIS with close/positive margins who underwent re-excision for the purpose of constructing a nomogram.

High endogenous CCL2 expression promotes the aggressive phenotype of human inflammatory breast cancer.

Inflammatory Breast Cancer (IBC) is a highly aggressive malignancy with distinct clinical and histopathological features whose molecular basis is unresolved. Here we describe a human IBC cell line, A3250, that recapitulates key IBC features in a mouse xenograft model, including skin erythema, diffuse tumor growth, dermal lymphatic invasion, and extensive metastases. A3250 cells express very high levels of the CCL2 chemokine and induce tumors enriched in macrophages.

Does previous history of cancer or atypia predict histologic upgrade for pure intraductal papillomas diagnosed via core biopsy? A study of 490 cases at a single institution.

Background: Management of pure intraductal papillomas (IDP) without atypia diagnosed on core needle biopsy (CNB) remains controversial given highly variable rates of upgrade in the literature.

Aim: We sought to identify clinical and histologic factors that predict upgrade to atypia or malignancy in a large population.

Methods And Results: A retrospective review was performed of all cases of pure IDP diagnosed on CNB and then surgically excised at a single institution from 2008 to 2018.

Secondary Invasive Breast Events among Patients with Hormone-Positive Breast Cancer and High-Risk Oncotype DX Recurrence Scores 26-30 and ≥31.

Background: The Oncotype DX Recurrence Score (ODx RS) is the most widely adopted genomic assay used to guide treatment for patients with early-stage, hormone-positive (HR+) breast cancer (BC), with higher scores predicting greater risk of recurrence and benefit from chemotherapy. Patients with ODx RS >25 typically recieve adjuvant chemotherapy; however, data regarding efficacy of chemotherapy for reducing recurrence in this population have been mixed.

Objectives: This study aimed to evaluate outcomes of patients with early-stage HR+ BC with high-risk ODx RS (26-30 and ≥31) in order to assess treatment patterns and outcomes.

Interobserver variability in the assessment of stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative invasive breast carcinoma influences the association with pathological complete response: the IVITA study.

High stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative breast cancer (TNBC) are associated with pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). Histopathological assessment of sTILs in TNBC biopsies is characterized by substantial interobserver variability, but it is unknown whether this affects its association with pCR. Here, we aimed to investigate the degree of interobserver variability in an international study, and its impact on the relationship between sTILs and pCR.

MRI Features of Free Liquid Silicone in the Transgender Female Breast.

Objective: To define MRI features of free liquid silicone injection (FLSI) of the breast in transgender women considering surgical management.

Methods: This study was IRB-approved. MRI images from transgender women with FLSI imaged between 2009 and 2019 were reviewed.

Measuring Invasive Breast Carcinoma on Core Biopsy-Is It Necessary?

Context.—: Pathologic tumor size is significant in the treatment of breast carcinoma and is routinely measured on excision.

Objective.

Response in breast vs axilla after neoadjuvant treatment and implications for nonoperative management of invasive breast cancer.

Improved imaging and neoadjuvant chemotherapy (NAT) have led to higher pathologic complete response rates (pCR) in patients with invasive breast cancer. This has questioned the necessity of surgery and axillary lymph node (ALN) dissection in these patients. Prospective clinical trials are implementing extensive core biopsies of the tumor bed of patients with clinical complete response as a means to identify and spare them breast surgery.

Histologic grading of breast carcinoma: a multi-institution study of interobserver variation using virtual microscopy.

Breast carcinoma grading is an important prognostic feature recently incorporated into the AJCC Cancer Staging Manual. There is increased interest in applying virtual microscopy (VM) using digital whole slide imaging (WSI) more broadly. Little is known regarding concordance in grading using VM and how such variability might affect AJCC prognostic staging (PS).

Evaluation of surgically excised breast tissue microstructure using wide-field optical coherence tomography.

Background: Currently, positive margins at lumpectomy contribute to health care cost, patient anxiety, and treatment delay. Multiple technology solutions are being explored with the aim of lowering re-excision rates for breast-conserving surgery (BCS). We examined wide-field optical coherence tomography (WF-OCT), an innovative adjunct intraoperative imaging tool for tissue visualization of margins.

Interobserver variability in upfront dichotomous histopathological assessment of ductal carcinoma in situ of the breast: the DCISion study.

Histopathological assessment of ductal carcinoma in situ, a nonobligate precursor of invasive breast cancer, is characterized by considerable interobserver variability. Previously, post hoc dichotomization of multicategorical variables was used to determine the "ideal" cutoffs for dichotomous assessment. The present international multicenter study evaluated interobserver variability among 39 pathologists who performed upfront dichotomous evaluation of 149 consecutive ductal carcinomas in situ.

Adenomyoepitheliomas of the Breast Frequently Harbor Recurrent Hotspot Mutations in PIK3-AKT Pathway-related Genes and a Subset Show Genetic Similarity to Salivary Gland Epithelial-Myoepithelial Carcinoma.

Adenomyoepitheliomas (AME) of the breast and epithelial-myoepithelial carcinomas (EMCs) of salivary gland are morphologically similar tumors defined by the presence of a biphasic population of ductal epithelial elements mixed with myoepithelial cells. We sought to explore the molecular profile of AMEs and determine whether they might also share the PLAG1, HMGA2, and HRAS alterations seen in EMCs. Tumor tissue from 19 AMEs was sequenced and analyzed using Ion AmpliSeq Cancer Hotspot Panel v2 covering ∼2800 COSMIC mutations across 50 cancer-related genes.

Evaluation of Biomarkers in Multiple Ipsilateral Synchronous Invasive Breast Carcinomas.

Context.—: The College of American Pathologists guidelines recommend testing additional tumor foci in multifocal invasive breast carcinomas for the biomarkers estrogen receptor (ER), progesterone receptor, and HER2 only if the carcinomas show different morphologies or grades.

Objective.

MYB rearrangement and immunohistochemical expression in adenomyoepithelioma of the breast: a comparison with adenoid cystic carcinoma.

Aims: Adenomyoepithelioma (AME) and adenoid cystic carcinoma (ACC) of the breast have been noted to occur simultaneously, raising the possibility that AME may represent a related or precursor lesion to ACC. ACC frequently harbours genetic rearrangement of the MYB gene. We sought to clarify the relationship between AME and ACC by comparing their rates of MYB expression by IHC and MYB rearrangement by FISH.

Not All Ductal Carcinomas In Situ Are Created IDLE (Indolent Lesions of Epithelial Origin).

Context.—: Mammographic screening has increased the incidence of ductal carcinoma in situ (DCIS), but this has not been accompanied by a decline in the incidence of invasive carcinoma (IC). Consequently, the surgical treatment of DCIS has recently been questioned, with some advocating only surveillance (with or without neoadjuvant endocrine therapy) after a core biopsy diagnosis of DCIS.

Observation versus excision of lobular neoplasia on core needle biopsy of the breast.

Purpose: Controversy surrounds management of lobular neoplasia (LN), [atypical lobular hyperplasia (ALH) or lobular carcinoma in situ (LCIS)], diagnosed on core needle biopsy (CNB). Retrospective series of pure ALH and LCIS reported "upgrade" rate to DCIS or invasive cancer in 0-40%. Few reports document radiologic/pathologic correlation to exclude cases of discordance that are the likely source of most upgrades, and there is minimal data on outcomes with follow-up imaging and clinical surveillance.

Invasive mucinous carcinoma of the breast and response patterns after neoadjuvant chemotherapy (NAC).

Aims: Neoadjuvant chemotherapy (NAC) is often used to treat localised invasive breast cancer. Invasive mucinous carcinoma (IMC) is considered to be an indolent form of invasive breast cancer, and is rarely treated with NAC. We report the largest series of IMCs treated with NAC, and report a characteristic, but not well recognised, pattern of pathological response.