Coalescing single-cell genomes and transcriptomes to decode breast cancer progression.

Understanding epithelial lineages of breast cancer and genotype-phenotype relationships requires direct measurements of the genome and transcriptome of the same single cells at scale. To achieve this, we developed wellDR-seq, a high-genomic-resolution, high-throughput method to simultaneously profile the genome and transcriptome of thousands of single cells. We profiled 33,646 single cells from 12 estrogen-receptor-positive breast cancers and identified ancestral subclones in multiple patients that showed a luminal hormone-responsive lineage, indicating a potential cell of origin.

High-throughput assay confirmation of a T-cell receptor pre-mRNA fragment as a blood-based inflammatory breast cancer biomarker.

Previous TGIRT-seq analysis of RNAs in Inflammatory Breast Cancer (IBC) patient tumors, peripheral blood mononuclear cells (PBMCs) and plasma identified a short T-cell receptor mRNA fragment () as a potential IBC biomarker that was detected in plasma samples from IBC patients but not patients with non-inflammatory breast cancer or healthy donors. Here, we traced the origin of this RNA fragment to IBC patient PBMCs and used a high-throughput RT-PCR/Cas12a assay with larger numbers of samples to confirm its prevalence in IBC patient PBMCs. Detection of this RNA was enhanced by T4 polynucleotide kinase treatment, indicating the presence of a 2',3'-cyclic phosphate.

Utility of whole-slide imaging for rapid evaluation of thyroid FNA: A multireader prospective study.

Background: Rapid on-site evaluation (ROSE) of thyroid fine-needle aspiration biopsy (FNAB) improves diagnostic adequacy and facilitates ancillary molecular testing. In this prospective, multireader study, the authors evaluated the feasibility of using whole-slide images (WSIs) for ROSE to determine specimen adequacy and preliminary categorization (according to The Bethesda System for Reporting Thyroid Cytopathology [Bethesda]) of image-guided thyroid FNABs compared with conventional light-microscopic (LM) examination of the same specimens in a referral cancer center.

Methods: The authors evaluated 98 ultrasound-guided thyroid FNAB cases.

Neoadjuvant HER2-targeted regimens with or without anthracyclines for HER2-positive inflammatory breast cancer: a multicenter retrospective study.

Purpose: Randomized clinical trials have shown no benefit from adding anthracyclines to neoadjuvant treatment for HER2-positive breast cancer; however, the efficacy in inflammatory breast cancer (IBC) is unknown. Here we compared pathologic response rates for preoperative regimens with or without anthracyclines in HER2-positive primary IBC.

Methods: We retrospectively reviewed patients diagnosed with HER2-positive primary IBC in 2014-2021 who received neoadjuvant therapy and modified radical mastectomy at MD Anderson Cancer Center, IBC Network institutions and Dana-Farber Cancer Institute.

Soluble E-cadherin Drives Brain Metastasis in Inflammatory Breast Cancer.

Unlabelled: The brain is a common site of relapse in inflammatory breast cancer (IBC), an E-cadherin positive, aggressive form of breast cancer. We found that elevated serum levels of soluble E-cadherin (sEcad), an 80-kDa fragment of E-cadherin, in patients with metastatic IBC correlated with poorer outcomes and increased rates of brain metastases. In our effort to understand the underlying mechanism, we discovered that sEcad binds to XIAP, an inhibitor of cell death, activating the pro-survival NF-kβ signaling in tumor cells.

Current landscape and emerging opportunities for using telecytology for rapid on-site assessment in cytopathology.

In recent years, cytopathology practices increasingly are considering the adoption of digital modalities to support remote rapid on-site evaluation (ROSE) of fine-needle aspiration biopsies. Currently, various digital options are available, each of which has unique advantages and limitations. This review covers all relevant aspects of telecytology for ROSE, including digital pathology options, operators, validation, quality assurance, reimbursement, and recommendations from professional organizations.

Inhibition of MCL-1 and MEK Overcomes MEK Inhibitor Resistance in Triple-Negative and Inflammatory Breast Cancers.

The MAPK pathway can drive resistance in highly aggressive breast cancers. Our previous work showed that the MEK inhibitor (MEKi) AZD6244 (selumetinib) prevented lung metastasis in a breast cancer xenograft model. In clinical studies, MEKis as single agents have had only modest activity against solid tumors due to the onset of resistance.

AXL promotes inflammatory breast cancer progression by regulating immunosuppressive macrophage polarization.

Background: Tumor-associated macrophages (TAMs) are key promoters of inflammatory breast cancer (IBC), the most aggressive form of breast cancer. The receptor tyrosine kinase AXL is highly expressed in various cancer types, including IBC, but its role in TAMs remains unexplored.

Methods: We examined the effects of AXL inhibitor TP-0903 on tumor growth and tumor microenvironment (TME) component M2 macrophages (CD206) in IBC and triple-negative breast cancer mouse models using flow cytometry and immunohistochemical staining.

Development of a multi-institutional dataset to validate a novel inflammatory breast cancer diagnostic score.

Background: Susan G. Komen, the Inflammatory Breast Cancer (IBC) Research Foundation, and the Milburn Foundation convened patient advocates, clinicians, and researchers to propose novel quantitative scoring rubrics for IBC diagnosis. In this study, we developed a multi-institutional clinical dataset to test and validate the proposed scoring system.

Selective Elimination of Breast Surgery for Invasive Breast Cancer: A Nonrandomized Clinical Trial.

Importance: Neoadjuvant systemic therapy (NST) has been associated with pathologic complete response (pCR) in up to 60% of breast cancers (BCs). The findings of this trial question the necessity of surgery.

Objective: To report preplanned 5-year efficacy outcomes evaluating radiotherapy alone without breast surgery in patients selected with image-guided vacuum assisted biopsy (VAB).

The Role of Fine-Needle Aspiration in Conjunction With Ancillary Immunophenotyping for Accurate Recognition of a Case of Splenosis in Perirectal Soft Tissue.

Splenosis is the implantation of splenic tissue into other organs following splenectomy or traumatic spleen injury. It typically manifests in the peritoneal cavity but can appear in other locations. Splenic nodules are often incidentally discovered during imaging, with nuclear scintigraphy being the gold standard for recognition.

Prospective and Retrospective Analysis of Whole-Slide Images of Sentinel and Targeted Lymph Node Frozen Sections in Breast Cancer.

Different digital modalities are currently available for frozen section (FS) evaluation in surgical pathology practice. However, there are limited studies that demonstrate the potential of whole-slide imaging (WSI) as a robust digital pathology option for FS diagnosis. In the current study, we compared the diagnostic accuracy achieved with WSI to that achieved with light microscopy (LM) for evaluating FSs of axillary sentinel lymph nodes (SLNs) and clipped lymph nodes (LNs) from patients with breast cancer using 2 modalities.

NOS inhibition sensitizes metaplastic breast cancer to PI3K inhibition and taxane therapy via c-JUN repression.

Metaplastic breast cancer (MpBC) is a highly chemoresistant subtype of breast cancer with no standardized therapy options. A clinical study in anthracycline-refractory MpBC patients suggested that nitric oxide synthase (NOS) inhibitor NG-monomethyl-l-arginine (L-NMMA) may augment anti-tumor efficacy of taxane. We report that NOS blockade potentiated response of human MpBC cell lines and tumors to phosphoinositide 3-kinase (PI3K) inhibitor alpelisib and taxane.

Trichorhinophalangeal syndrome 1 expression in breast and nonbreast metastases from Müllerian, lung, gastrointestinal tract, and pancreatic primary tumors by immunohistochemistry with cytology cell block specimens.

Background: Trichorhinophalangeal syndrome 1 (TRPS1) expression in primary breast and other solid tumors has been investigated but its role as a marker in metastatic tumors is unclear. The objective of this study was to evaluate the sensitivity and specificity of TRPS1 as a breast cancer immunomarker in metastatic tumors that originated from breast, Müllerian, lung, gastrointestinal (GI), and pancreatic primary tumors with cell blocks from fine-needle aspiration (FNA) and effusion specimens.

Methods: Cell blocks were immunostained with anti-TRPS1 monoclonal antibody (clone EPR16171).

Feasibility of breast conserving surgery alone in HER2-positive exceptional responders to neoadjuvant systemic therapy.

It is unknown if radiation therapy provides additional benefit among patients who achieve pathologic complete response (pCR) following neoadjuvant systemic therapy (NST). We sought to assess feasibility of radiation omission after breast conserving surgery in early-stage, node-negative, HER2+ breast cancer patients with pCR after NST. This was a single-arm study of women 30 years and older with cT2N0 disease based on imaging.

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.

Epigenetic activation of SOX11 is associated with recurrence and progression of ductal carcinoma in situ to invasive breast cancer.

Background: Risk of recurrence and progression of ductal carcinoma in situ (DCIS) to invasive cancer remains uncertain, emphasizing the need for developing predictive biomarkers of aggressive DCIS.

Methods: Human cell lines and mouse models of disease progression were analyzed for candidate risk predictive biomarkers identified and validated in two independent DCIS cohorts.

Results: RNA profiling of normal mammary and DCIS tissues (n = 48) revealed that elevated SOX11 expression correlates with MKI67, EZH2, and DCIS recurrence score.

Concordance between pathologists and between specimen types in detection of HER2-low breast carcinoma by immunohistochemistry.

Context: Recent clinical trials indicate that HER2-targeted therapy may benefit HER2-low breast cancer patients including HER2 score 1+ or 2+ and no gene amplification. Concordance between pathologists and between core biopsy and surgical excision in establishing HER2-low status was evaluated.

Design: 57 patients with HER2 negative breast cancer (IHC 0, 1+, or 2+, no gene amplification) by core biopsy were included.

Immunohistochemical assessment of HER2 low breast cancer: interobserver reproducibility and correlation with digital image analysis.

Purpose: The recent findings from the DESTINY-Breast04 trial highlighted the clinical importance of distinguishing between HER2 immunohistochemistry (IHC) scores 0 and 1 + in metastatic breast cancer (BC). However, pathologist interpretation of HER2 IHC scoring is subjective, and standardized methodology is needed. We evaluated the consistency of HER2 IHC scoring among pathologists and the accuracy of digital image analysis (DIA) in interpreting HER2 IHC staining in cases of HER2-low BC.

Recommendations for Performance Evaluation of Machine Learning in Pathology: A Concept Paper From the College of American Pathologists.

Context.—: Machine learning applications in the pathology clinical domain are emerging rapidly. As decision support systems continue to mature, laboratories will increasingly need guidance to evaluate their performance in clinical practice.

Patient Interest in Exploring Nonsurgical Treatment Approaches for Early-Stage Breast Cancer: A Qualitative Study.

Purpose: Advances in radiation therapy have enabled the ability to deliver ablative treatments, but there has been limited application of these treatments to early-stage breast cancers with a goal of omitting surgery. The purpose of this study was to explore patient interest in pursuing nonsurgical treatment approaches for their early-stage breast cancer.

Methods And Materials: We conducted a qualitative study involving interviews with 21 patients with early-stage breast cancer who were eligible for participation in a phase 2 clinical trial offering omission of definitive surgery.