Active Monitoring With or Without Endocrine Therapy for Low-Risk Ductal Carcinoma In Situ: The COMET Randomized Clinical Trial.

Importance: Active monitoring for low-risk ductal carcinoma in situ (DCIS) of the breast has been proposed as an alternative to guideline-concordant care, but the safety of this approach is unknown.

Objective: To compare rates of invasive cancer in patients with low-risk DCIS receiving active monitoring vs guideline-concordant care.

Design, Setting, And Participants: Prospective, randomized noninferiority trial enrolling 995 women aged 40 years or older with a new diagnosis of hormone receptor-positive grade 1 or grade 2 DCIS without invasive cancer at 100 US Alliance Cancer Cooperative Group clinical trial sites from 2017 to 2023.

Serous-like breast carcinomas: immunophenotypic, genetic, and clinicopathologic characterization of a morphologically distinct group of tumours.

Aims: Unusual morphologic patterns of breast carcinomas can raise diagnostic consideration for metastasis or special breast cancer subtypes with management implications. We describe rare invasive breast cancers that mimic serous carcinoma of the gynaecologic tract (serous-like breast carcinomas, SLBC) and characterize their clinicopathologic, immunophenotypic, and genetic features.

Methods And Results: All patients were female (n = 15, median age 49 years) without a history of gynaecologic malignancy.

An estrogen receptor signaling transcriptional program linked to immune evasion in human hormone receptor-positive breast cancer.

Unlabelled: T cells are generally sparse in hormone receptor-positive (HR+) breast cancer, potentially due to limited antigen presentation, but the driving mechanisms of low T cell abundance remains unclear. Therefore, we defined and investigated programs ('gene modules'), related to estrogen receptor signaling (ERS) and immune signaling using bulk and single-cell transcriptome and multiplexed immunofluorescence of breast cancer tissues from multiple clinical sources and human cell lines. The ERS gene module, dominantly expressed in cancer cells, was negatively associated with immune-related gene modules TNFα/NF-κB signaling and type-I interferon (IFN-I) response, which were expressed in distinct stromal and immune cell types, but also, in part, expressed and preserved as a cancer cell-intrinsic mechanisms.

Integrative Multiomic Profiling of Triple-Negative Breast Cancer for Identifying Suitable Therapies.

Purpose: Triple-negative breast cancer (TNBC) is a heterogeneous disease that carries the poorest prognosis of all breast cancers. Although novel TNBC therapies in development are frequently targeted toward tumors carrying a specific genomic, transcriptomic, or protein biomarker, it is poorly understood how these biomarkers are correlated.

Experimental Design: To better understand the molecular features of TNBC and their correlation with one another, we performed multimodal profiling on a cohort of 95 TNBC.

U.S. payer budget impact of using an AI-augmented cancer risk discrimination digital histopathology platform to identify high-risk of recurrence in women with early-stage invasive breast cancer.

Aims: Use of gene expression signatures to predict adjuvant chemotherapy benefit in women with early-stage breast cancer is increasing. However, high cost, limited access, and eligibility for these tests results in the adoption of less precise assessment approaches. This study evaluates the cost impact of PreciseDx Breast (PDxBr), an AI-augmented histopathology platform that assesses the 6-year risk of recurrence in early-stage invasive breast cancer patients to help improve informed use of adjuvant chemotherapy.

Effect of testosterone therapy on breast tissue composition and mammographic breast density in trans masculine individuals.

Background: The effect of gender-affirming testosterone therapy (TT) on breast cancer risk is unclear. This study investigated the association between TT and breast tissue composition and breast tissue density in trans masculine individuals (TMIs).

Methods: Of the 444 TMIs who underwent chest-contouring surgeries between 2013 and 2019, breast tissue composition was assessed in 425 TMIs by the pathologists (categories of lobular atrophy and stromal composition) and using our automated deep-learning algorithm (% epithelium, % fibrous stroma, and % fat).

Dataset for reporting of the invasive carcinoma of the breast: recommendations from the International Collaboration on Cancer Reporting (ICCR).

Background And Objectives: Current national or regional guidelines for the pathology reporting on invasive breast cancer differ in certain aspects, resulting in divergent reporting practice and a lack of comparability of data. Here we report on a new international dataset for the pathology reporting of resection specimens with invasive cancer of the breast. The dataset was produced under the auspices of the International Collaboration on Cancer Reporting (ICCR), a global alliance of major (inter-)national pathology and cancer organizations.

Integration of Pathological Criteria and Immunohistochemical Evaluation for Invasive Lobular Carcinoma Diagnosis: Recommendations From the European Lobular Breast Cancer Consortium.

Invasive lobular carcinoma (ILC) is the second most frequent type of breast cancer (BC) and its peculiar morphology is mainly driven by inactivation of CDH1, the gene coding for E-cadherin cell adhesion protein. ILC-specific therapeutic and disease-monitoring approaches are gaining momentum in the clinic, increasing the importance of accurate ILC diagnosis. Several essential and desirable morphologic diagnostic criteria are currently defined by the World Health Organization, the routine use of immunohistochemistry (IHC) for E-cadherin is not recommended.

A dedicated structured data set for reporting of invasive carcinoma of the breast in the setting of neoadjuvant therapy: recommendations from the International Collaboration on Cancer Reporting (ICCR).

Aims: The International Collaboration on Cancer Reporting (ICCR), a global alliance of major (inter-)national pathology and cancer organisations, is an initiative aimed at providing a unified international approach to reporting cancer. ICCR recently published new data sets for the reporting of invasive breast carcinoma, surgically removed lymph nodes for breast tumours and ductal carcinoma in situ, variants of lobular carcinoma in situ and low-grade lesions. The data set in this paper addresses the neoadjuvant setting.

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.

Qualification of a multiplexed tissue imaging assay and detection of novel patterns of HER2 heterogeneity in breast cancer.

Emerging data suggests that HER2 intratumoral heterogeneity (ITH) is associated with therapy resistance, highlighting the need for new strategies to assess HER2 ITH. A promising approach is leveraging multiplexed tissue analysis techniques such as cyclic immunofluorescence (CyCIF), which enable visualization and quantification of 10-60 antigens at single-cell resolution from individual tissue sections. In this study, we qualified a breast cancer-specific antibody panel, including HER2, ER, and PR, for multiplexed tissue imaging.

Defining the Biology of Estrogen Receptor-Low-Positive Breast Cancer.

Background: We sought to better define estrogen receptor-low-positive (ER-low+) breast cancer biology and determine the utility of the Oncotype DX Breast Recurrence Score (RS) assay in this population.

Methods: Patients with information regarding percentage ER positivity and PAM50 subtype were identified in The Cancer Genome Atlas (TCGA) and subtype distribution was determined. Next, patients with ER-low+ (ER 1-10%), HER2- breast cancer undergoing upfront surgery with known RS result were identified in the National Cancer Database (NCDB) and our institutional Dana-Farber Brigham Cancer Center (DF/BCC) database; RS distribution was examined.

Salivary Gland-like Tumors of the Breast.

Context: The World Health Organization classification of tumors of the breast recognizes several special type carcinomas and benign lesions with features comparable to those of salivary gland tumors.

Objective: To discuss the histologic, immunophenotypic, molecular, and clinical features of salivary gland-like carcinomas of the breast. These breast tumors are often negative for hormone receptors and human epidermal growth factor receptor 2 (HER2), that is, triple-negative, but they generally have a much better prognosis than triple-negative breast carcinomas of no special type.

ESMO expert consensus statements (ECS) on the definition, diagnosis, and management of HER2-low breast cancer.

Human epidermal growth factor receptor 2 (HER2)-low breast cancer has recently emerged as a targetable subset of breast tumors, based on the evidence from clinical trials of novel anti-HER2 antibody-drug conjugates. This evolution has raised several biological and clinical questions, warranting the establishment of consensus to optimally treat patients with HER2-low breast tumors. Between 2022 and 2023, the European Society for Medical Oncology (ESMO) held a virtual consensus-building process focused on HER2-low breast cancer.

Toker Cell Hyperplasia in the Nipple-Areolar Complex of Transmasculine Individuals.

We previously reported breast histopathologic features associated with testosterone therapy in transmasculine chest-contouring surgical specimens. During that study, we observed a high frequency of intraepidermal glands in the nipple-areolar complex (NAC) formed by Toker cells. This study reports Toker cell hyperplasia (TCH)-the presence of clusters of Toker cells consisting of at least 3 contiguous cells and/or glands with lumen formation-in the transmasculine population.

NR4A3 Expression Is Consistently Absent in Acinic Cell Carcinomas of the Breast: A Potential Nosologic Shift.

Acinic cell carcinoma (AciCC) is a tumor that is recognized in both the breast and salivary glands. Recently, the recurrent genomic rearrangement, t(4;9)(q13;q31) was identified in salivary AciCC that results in constitutive upregulation of the nuclear transcription factor NR4A3, which can be detected by immunohistochemistry. In this study, we sought to evaluate NR4A3 expression in breast AciCC using immunohistochemistry.

Validation and real-world clinical application of an artificial intelligence algorithm for breast cancer detection in biopsies.

Breast cancer is the most common malignant disease worldwide, with over 2.26 million new cases in 2020. Its diagnosis is determined by a histological review of breast biopsy specimens, which can be labor-intensive, subjective, and error-prone.

Results of a worldwide survey on the currently used histopathological diagnostic criteria for invasive lobular breast cancer.

Invasive lobular carcinoma (ILC) represents the second most common subtype of breast cancer (BC), accounting for up to 15% of all invasive BC. Loss of cell adhesion due to functional inactivation of E-cadherin is the hallmark of ILC. Although the current world health organization (WHO) classification for diagnosing ILC requires the recognition of the dispersed or linear non-cohesive growth pattern, it is not mandatory to demonstrate E-cadherin loss by immunohistochemistry (IHC).

Impact of the Histologic Pattern of Residual Tumor After Neoadjuvant Chemotherapy on Recurrence and Survival in Stage I-III Breast Cancer.

Background: Additional risk-stratification measures are needed in breast cancer patients with residual disease after neoadjuvant chemotherapy (NAC). We aimed to describe oncologic outcomes in a modern cohort treated with NAC, and evaluate the prognostic value of histologic pattern of residual tumor.

Patients And Methods: We included patients with stage I-III breast cancer treated with NAC and surgery from 2004 to 2014.

Presence of Non-classic LCIS Is Not a Contraindication to Breast Conservation in Patients with Concomitant Invasive Breast Cancer or DCIS.

Background: Non-classic lobular carcinoma in situ (NC-LCIS) represents a spectrum of lesions, histologically distinct from classic LCIS (C-LCIS) and ductal carcinoma in situ (DCIS). Several studies have reported on the safety of breast conservation (BCS) in patients with DCIS or invasive breast cancer and concomitant C-LCIS, yet there are no data addressing this question for patients with concomitant NC-LCIS. We evaluated local recurrence (LR) after BCS in patients with DCIS or invasive cancer and concomitant NC-LCIS.