Human epidermal growth factor receptor 2 (HER2)-positive breast carcinoma (BC) encompasses a spectrum of molecular subtypes, characterized by varying HER2/CEP17 ratios and HER2 copy numbers, influencing responses to anti-HER2 therapy. This study stratified HER2 fluorescence in situ hybridization (FISH)-positive patients into 3 distinct groups-group 1 with high copy number (G1-HC: ratio ≥2, copy number ≥6), group 1 with low copy number (G1-LC: ratio ≥2, copy number ≥4 and <6), and group 3 (G3: ratio <2.0, copy number ≥6.
View Article and Find Full Text PDFObjectives: The American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) recommend cold ischemia time (cIT) be <60 min, and formalin fixation time (FFT) 6-72 h, to optimize immunohistochemistry (IHC) based on breast cancer data. We assessed whether cIT and FFT impact IHC in endometrial cancer (EC), and determined which factors affect cIT and FFT.
Methods: Surgical EC cases from 2019 to 2023 were reviewed.
Accurate recurrence risk stratification is crucial for optimizing treatment plans for breast cancer patients. Current prognostic tools like Oncotype DX (ODX) offer valuable genomic insights for HR+/HER2- patients but are limited by cost and accessibility, particularly in underserved populations. In this study, we present Deep-BCR-Auto, a deep learning-based computational pathology approach that predicts breast cancer recurrence risk from routine H&E-stained whole slide images (WSIs).
View Article and Find Full Text PDFAims: 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.
View Article and Find Full Text PDFInflammatory breast cancer (IBC) poses an ongoing challenge as rates of disease recurrence and mortality remain high compared to stage-matched controls. However, frontline therapy has evolved through the years, including the widespread use of neoadjuvant chemotherapy (NAC) given the prognostic importance of pathologic complete response (pCR). Due to these sweeping changes, we need new data to assess current recurrence and survival outcomes for locally advanced IBC in the context of matched non-inflammatory controls.
View Article and Find Full Text PDFIn DESTINY-Breast04 (DB-04), safety and efficacy of HER2-targeted antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) in previously treated HER2-low unresectable/metastatic breast cancer were established. This manuscript describes the analytical validation of PATHWAY Anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody (PATHWAY HER2 (4B5)) to assess HER2-low status and its clinical performance in DB-04. Preanalytical processing and tissue staining parameters were evaluated to determine their impact on HER2 scoring.
View Article and Find Full Text PDFAdv Anat Pathol
November 2023
In response to recent clinical trials that demonstrate the clinical benefit of antibody-drug conjugate drug therapy in breast cancer (BC) with human epidermal growth factor 2 (HER2) immunohistochemical scores of 1+ or 2+ and negative in situ hybridization results, a new concept of "HER2-low BC" has emerged to describe this newly relevant therapeutic category of BC. Clinical recognition of HER2-low BC has caused a paradigm shift in the therapeutic landscape and management of patients with BC and resulted in rapid changes in clinical practice guidelines. In addition the American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) recently updated their HER2 Guidelines Recommendations to specifically address HER2-low BC.
View Article and Find Full Text PDFThe early diagnosis of lymph node metastasis in breast cancer is essential for enhancing treatment outcomes and overall prognosis. Unfortunately, pathologists often fail to identify small or subtle metastatic deposits, leading them to rely on cytokeratin stains for improved detection, although this approach is not without its flaws. To address the need for early detection, multiple-instance learning (MIL) has emerged as the preferred deep learning method for automatic tumor detection on whole slide images (WSIs).
View Article and Find Full Text PDFIntroduction: The immunomodulatory impact of corticosteroids and concurrent chemotherapy is poorly understood within triple-negative breast cancer (TNBC). On a biochemical level, steroids have been linked to the signaling of chemotherapy-resistant pathways. However, on a clinical level, steroids play an essential role in chemotherapy tolerance through the prevention of chemotherapy-induced nausea and vomiting (CINV) and hypersensitivity reactions.
View Article and Find Full Text PDFContext.—: 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.
View Article and Find Full Text PDFBreast cancer is the most common malignancy in women, with over 40,000 deaths annually in the United States alone. Clinicians often rely on the breast cancer recurrence score, Oncotype DX (ODX), for risk stratification of breast cancer patients, by using ODX as a guide for personalized therapy. However, ODX and similar gene assays are expensive, time-consuming, and tissue destructive.
View Article and Find Full Text PDFHuman epidermal growth factor receptor 2 (HER2)-low breast cancer, defined by an immunohistochemical (IHC) score of 1+ or 2+ with negative in situ hybridization, is emerging as a predictive marker for the use of the antibody-drug conjugate. To understand how this category differs from HER2-zero cases, we investigated clinicopathological characteristics and HER2 fluorescence in situ hybridization results in a large cohort of 1309 continuous HER2-negative invasive breast carcinomas from 2018 to 2021 evaluated by the Food and Drug Administration-approved HER2 IHC test. Additionally, we compared Oncotype DX recurrence scores and HER2 mRNA expression between HER-low and HER2-zero cases in a separate cohort of 438 estrogen receptor-positive (ER+) early-stage breast carcinoma cases from 2014 to 2016.
View Article and Find Full Text PDFIntravascular papillary endothelial hyperplasia (Masson's Tumor) is a rare benign endothelial vascular lesion that can mimic angiosarcoma if not properly recognized. It represents less than 2% of all vascular tumors, but has been seen in the postradiation setting, which also makes differentiating it from angiosarcoma crucial. It is classically characterized as a circumscribed, intravascular mass that is hypoechoic on ultrasound, and T1 isointense and T2 heterogenous on MRI with variable enhancement.
View Article and Find Full Text PDFJ Pathol Transl Med
May 2022
The 5th edition WHO Classification of Breast Tumours (2019) has introduced changes to our practices. Highlights are presented below, with a focus on modifications to morphological subtype categorization. In addition, we summarize important updates to ER and PR testing made in the 2020 ASCO/CAP guidelines, and briefly discuss PD-L1 and Ki-67 testing in breast cancer.
View Article and Find Full Text PDFAnastomosing hemangioma (AH), a rare benign genitourinary tract hemangioma is subject to frequent misdiagnosis due to its rarity and clinical, histological, and immunohistochemical similarities it shares with several diagnoses, including well-differentiated angiosarcoma (AS). This is particularly true of angiosarcoma, nearly identical to AH when presented in tissue samples of limited size. Lack of specific clinical and radiologic manifestations on initial preoperative assessment, coupled with limited diagnostic experience or awareness, can lead to misinterpretation of this entity, potentially leading to unnecessary clinical management.
View Article and Find Full Text PDFBackground: Very few studies have investigated mismatch repair (MMR) deficiency in breast carcinoma (BC) in clinical setting. Given the recent approval of Pembrolizumab for solid tumors with MMR deficiency, we screened clinically advanced breast carcinoma patients for immunotherapy by examining their MMR status.
Patients And Methods: The cohort consisted of 163 clinical advanced BCs, including 5 primary, 14 locally recurrent, and 144 metastatic BCs.
Ductal carcinoma in situ (DCIS) in males is rare, and there are limited data aimed at understanding the adequate workup, imaging, and follow-up for men who present with breast masses. Attention should be given to black men who have a higher cancer risk and worse prognosis than white male counterparts.
View Article and Find Full Text PDFInvasive lobular carcinoma (ILC) accounts for 10% to 15% of breast cancers in the United States, 80% of which are estrogen receptor (ER)-positive, with an unusual metastatic pattern of spread to sites such as the serosa, meninges, and ovaries, among others. Lobular cancer presents significant challenges in detection and clinical management given its multifocality and multicentricity at presentation. Despite the unique features of ILC, it is often lumped with hormone receptor-positive invasive ductal cancers (IDC); consequently, ILC screening, treatment, and follow-up strategies are largely based on data from IDC.
View Article and Find Full Text PDFIntroduction: While the long-term oncologic safety of robot-assisted nipple sparing mastectomy (RNSM) remains to be elucidated, histologically detected residual breast tissue (RBT) can be a surrogate for oncologically sound mastectomy. The objective of this study is to determine the presence of RBT after RNSM.
Methods: Between August 2019-January 2020, we completed 5 cadaveric RNSMs.
Objective: The primary objective of this study was to delineate differences in management, overall and distant disease-free survival in males diagnosed with breast cancer and treated at The Ohio State University Comprehensive Cancer Center as compared to comprehensively matched female subjects. Secondary objectives included assessment of clinical and histopathologic features and recurrence score, as measured by Oncotype DX and the modified Magee equation #2.
Materials And Methods: This single institution retrospective study compared male and comprehensively matched female patients (1:2) with stage I-III breast cancer between 1994 and 2014.
Primary small cell carcinoma of the breast (SCCB) is a rare tumor subtype comprising <0.1% of all breast carcinomas. Here we present a case of thyroid transcription factor-1 (TTF-1) positive SCCB that recurred within 3 years of diagnosis in the lung and lymph nodes.
View Article and Find Full Text PDFBackground: Subjective qualitative descriptors are sometimes used to describe atypical breast lesions diagnosed on core needle biopsy (CNB) which are limited in extent. In clinical practice, this terminology is used to imply a lower expected risk of upgrade on surgical excision (EXC). It is uncertain how subjective terminology impacts clinical management.
View Article and Find Full Text PDFObjectives: The 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) human epidermal growth factor receptor 2 (HER2) guideline focused update revises the HER2 scoring criteria. We evaluated the impact on HER2 rates in breast carcinoma diagnosed at our center.
Methods: In a retrospective series of breast core biopsies with invasive carcinoma diagnosed between 2014 and 2017 (n = 1,350), HER2 status was classified according to 2013 and 2018 ASCO/CAP guidelines and changes in HER2 status identified.
This unusual case of concurrent eccrine adenocarcinoma, phyllodes tumor, and multinodular goiter serves to alert the oncologic community to the high prevalence of second cancers after childhood radiotherapy. Increased surveillance and index of suspicion are recommended to successfully diagnose and treat second primary cancers in this vulnerable population.
View Article and Find Full Text PDFIn metastatic breast cancer (MBC), it can be difficult to establish the origin if the primary tumor is triple negative or if there is a loss of biomarker expression. SOX10 expression has been reported in primary triple-negative breast cancer but is poorly studied in metastatic lesions. In this study, the diagnostic utility of a panel of SOX10, GATA3, and androgen receptor (AR) in MBC negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 was evaluated and compared with the expression of these markers in the matched primary breast cancer.
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