Breast biomarkers evolution between primary and distant metastasis: incidence and significance.

Aims: To evaluate the evolution when breast cancer (BC) is classified as three clinical profiles and five clinical profiles by incorporating human epidermal growth factor 2 (HER2)-low to the biomarkers' profile.

Methods And Results: BC with distant metastasis that has document hormonal receptors (HR) (positive, negative) and HER2 (positive, low, zero) results were included (n = 161). Cases were categorised into three clinical profiles (HR-positive/HER2-negative, HER2-positive and TNBC) and five (HR-positive/HER2-zero, HR-positive/HER2-low, HR-negative/HER2-zero, HR-negative/HER2-low, HR-positive or negative/HER2-positive).

Detrimental Impact of Chemotherapy Dose Reduction or Discontinuation in Early Stage Triple-Negative Breast Cancer Treated With Pembrolizumab and Neoadjuvant Chemotherapy: A Multicenter Experience.

Background: Pembrolizumab combined with neoadjuvant chemotherapy (NAC) is the current standard of care in early stage triple-negative breast cancer (TNBC) based on higher event-free survival and pathological complete response (pCR) in Keynote-522 (KN-522) clinical trial. However, this aggressive five-drug regimen is associated with increased risks for immune-related adverse events (irAEs). We investigated real-world clinical outcomes and toxicity of this regimen as well as factors predictive of pCR and irAEs.

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.

Infiltration of Common Myeloid Progenitor (CMP) Cells is Associated With Less Aggressive Tumor Biology, Lower Risk of Brain Metastasis, Better Response to Immunotherapy, and Higher Patient Survival in Breast Cancer.

Objective: To investigate the clinical relevance of common myeloid progenitor (CMP) cells in breast tumor microenvironment (TME).

Background: The role of rare cells in TME is less studied. In Silico transcriptomic analyses of real-world data enable us to detect and quantify rare cells, including CMP cells.

Validation Study of the Newly Proposed Refined Diagnostic Criteria for Malignant Phyllodes Tumor With 136 Borderline and Malignant Phyllodes Tumor Cases.

The World Health Organization (WHO) diagnostic criteria for malignant phyllodes tumor (MPT) may miss a significant number of MPTs with metastatic potential. New refined diagnostic criteria (Refined Criteria) for MPT were recently proposed. The aim of this study is to validate the Refined Criteria.

Diagnosis and Management of Desmoid Fibromatosis of the Breast.

Desmoid fibromatosis of the breast (also known as desmoid tumor of the breast) is a rare entity infrequently encountered by oncologists and surgeons caring for patients with breast disease. The current body of literature is highly reliant on case series and extrapolations from other sites of desmoid tumor-related disease. Much remains unclear regarding the pathological origins, natural history, and response to treatment of this condition.

Emerging measurements for tumor-infiltrating lymphocytes in breast cancer.

Tumor-infiltrating lymphocytes are a general term for lymphocytes or immune cells infiltrating the tumor microenvironment. Numerous studies have demonstrated tumor-infiltrating lymphocytes to be robust prognostic and predictive biomarkers in breast cancer. Recently, immune checkpoint inhibitors, which directly target tumor-infiltrating lymphocytes, have become part of standard of care treatment for triple-negative breast cancer.

Clinical, Epidemiologic, and Pathologic Significance of ERBB2-Low Expression in Breast Cancer.

Importance: It is unclear whether breast cancer (BC) with low ERBB2 expression (ERBB2-low) is a distinct clinical, pathological, and epidemiological entity from BC classified as no ERBB2 expression (ERBB2-negative).

Objective: To evaluate the clinical, pathological, and epidemiologic features of BC with ERBB2-low expression compared with ERBB2-negative BC in a large population study.

Design, Setting, And Participants: This cohort study was conducted as part of the Pathways Study, a prospective, racially and ethnically diverse cohort study of women with BC enrolled between 2006 and 2013 in Kaiser Permanente Northern California (KPNC).

Selective breast/gynecologic pathology fellowship training in the United States: Experience of program directors.

Published data on combined breast and gynecologic [breast/gyn] surgical pathology fellowship training programs are limited. Our study aimed to survey the landscape of such fellowships in the United States (US), including specific information about their characteristics and the educational activities therein. Using web searches, we identified programs offering combined breast/gyn surgical pathology fellowship training.

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.

Racial and Ethnic Disparity in Preoperative Chemosensitivity and Survival in Patients With Early-Stage Breast Cancer.

Importance: It remains unclear what survival benefit is associated with preoperative chemosensitivity after receiving neoadjuvant chemotherapy (NACT) among patients with resectable breast cancer from diverse racial and ethnic backgrounds.

Objective: To investigate racial and ethnic disparities in chemosensitivity and association with survival in patients with early-stage breast cancer.

Design, Setting, And Participants: This retrospective cohort study queried data from the National Cancer Database (NCDB) between calendar years 2010 and 2018.

The Evolving Approach to Breast Cancer: Moving toward De-Escalating Treatment and Personalized Medicine.

In recent years, more attention has been directed to personalized medicine in the management and treatment of breast cancer (BC) [...

Intratumoral Tumor Infiltrating Lymphocytes (TILs) are Associated With Cell Proliferation and Better Survival But Not Always With Chemotherapy Response in Breast Cancer.

Objective: To investigate the clinical relevance of intratumoral tumor infiltrating lymphocytes (TILs) in breast cancer as measured by computational deconvolution of bulk tumor transcriptomes.

Summary Background Data: Commonly assessed TILs, located in tumor stroma without direct contact with cancer cells (stromal TILs), correlate with breast cancer treatment response and survival. The clinical relevance of intratumoral TILs has been less studied partly due to their rarity; however, they may have nonnegligible effects given their direct contact with cancer cells.

DNA methylation differences in noncoding regions in ER negative breast tumors between Black and White women.

Introduction: Incidence of estrogen receptor (ER)-negative breast cancer, an aggressive tumor subtype associated with worse prognosis, is higher among African American/Black women than other US racial and ethnic groups. The reasons for this disparity remain poorly understood but may be partially explained by differences in the epigenetic landscape.

Methods: We previously conducted genome-wide DNA methylation profiling of ER- breast tumors from Black and White women and identified a large number of differentially methylated loci (DML) by race.

Metaplastic Breast Carcinoma Revisited; Subtypes Determine Outcomes: Comprehensive Pathologic, Clinical, and Molecular Review.

Metaplastic breast carcinoma (MpBC) is a heterogeneous group of tumors that clinically could be divided into low risk and high risk. It is important to recognize the different types of MpBC, as the high-risk subtypes have worse clinical outcomes than triple-negative breast cancer. It is important for the pathologist to be aware of the MpBC entities and use the proposed algorithms (morphology and immunohistochemistry) to assist in rendering the final diagnosis.

An epigenome-wide analysis of socioeconomic position and tumor DNA methylation in breast cancer patients.

Background: Disadvantaged socioeconomic position (SEP), including lower educational attainment and household income, may influence cancer risk and outcomes. We hypothesized that DNA methylation could function as an intermediary epigenetic mechanism that internalizes and reflects the biological impact of SEP.

Methods: Based on tumor DNA methylation data from the Illumina 450 K array from 694 breast cancer patients in the Women's Circle of Health Study, we conducted an epigenome-wide analysis in relation to educational attainment and household income.

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.

Association Between Recreational Physical Activity and mTOR Signaling Pathway Protein Expression in Breast Tumor Tissue.

Unlabelled: Physical activity (PA) is associated with decreased signaling in the mTOR pathway in animal models of mammary cancer, which may indicate favorable outcomes. We examined the association between PA and protein expression in the mTOR signaling pathway in breast tumor tissue. Data on 739 patients with breast cancer, among which 125 patients had adjacent-normal tissue, with tumor expression for mTOR, phosphorylated (p)-mTOR, p-AKT, and p-P70S6K were analyzed.

Clinicopathologic Predictors of Clinical Outcomes in Mammary Adenoid Cystic Carcinoma: A Multi-institutional Study.

Adenoid cystic carcinoma (AdCC) is an uncommon type of invasive breast carcinoma with a favorable prognosis. However, some cases are aggressive. The study aims to define the clinicopathologic predictors of outcome.

Results and lessons from dual extraction of DNA and RNA from formalin-fixed paraffin-embedded breast tumor tissues for a large Cancer epidemiologic study.

Background: The use of archived formalin-fixed paraffin-embedded (FFPE) tumor tissues has become a common practice in clinical and epidemiologic genetic research. Simultaneous extraction of DNA and RNA from FFPE tissues is appealing but can be practically challenging. Here we report our results and lessons learned from processing FFPE breast tumor tissues for a large epidemiologic study.

Greater Body Fatness Is Associated With Higher Protein Expression of LEPR in Breast Tumor Tissues: A Cross-Sectional Analysis in the Women's Circle of Health Study.

Background: The mechanisms underlying the association of overall and central body fatness with poorer breast cancer outcomes remain unclear; altered gene and/or protein expression of the adipokines and their receptors in breast tumors might play a role.

Methods: In a sample of Black and White women with primary invasive breast cancer, we investigated associations of body mass index (BMI), waist circumference, hip circumference, waist-to-hip ratio (WHR), fat mass index (FMI), and percent body fat with protein expression (log-transformed, n = 722) and gene expression (log2-transformed, n = 148) of leptin (LEP), leptin receptor (LEPR), adiponectin (ADIPOQ), and adiponectin receptors 1 and 2 (ADIPOR1, ADIPOR2). Multivariable linear models, adjusting for race, menopausal status, and estrogen receptor status, were used to assess these associations, with Bonferroni correction for multiple comparisons.

Tumor-associated mononuclear cells in the tumor bed of triple-negative breast cancer associate with clinical outcomes in the post-neoadjuvant chemotherapy setting.

Purpose: To evaluate the clinical role of tumor-associated macrophages, including foamy (FM) and hemosiderin-laden macrophages (HLM) in the tumor bed (TB) of triple-negative breast cancer (TNBC) post-neoadjuvant chemotherapy (NACT).

Methods: We conducted a pathologic review of 129 women, diagnosed with TNBC between 2002 and 2016 at our institute. The residual cancer burden (RCB) was calculated.