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Background: Breast cancer (BC) in women aged ≤40 years carrying germline pathogenetic variants (PVs) in BRCA1/2 genes is infrequent but often associated with aggressive features. Human epidermal growth factor receptor 2 (HER2)-low-expressing BC has recently emerged as a novel therapeutic target but has not been characterized in this rare patient subset., Methods: Women aged ≤40 years with newly diagnosed early-stage HER2-negative BC (HER2-0 and HER2-low) and germline BRCA1/2 PVs from 78 health care centers worldwide were retrospectively included. Chi-square test and Student t-test were used to describe variable distribution between HER2-0 and HER2-low. Associations with HER2-low status were assessed with logistic regression. Kaplan-Meier method and Cox regression analysis were used to assess disease-free survival (DFS) and overall survival. Statistical significance was considered for p ≤ .05., Results: Of 3547 included patients, 32.3% had HER2-low BC, representing 46.3% of hormone receptor-positive and 21.3% of triple-negative (TN) tumors. HER2-low vs. HER2-0 BC were more often of grade 1/2 (p < .001), hormone receptor-positive (p < .001), and node-positive (p = .003). BRCA2 PVs were more often associated with HER2-low than BRCA1 PVs (p < .001). HER2-low versus HER2-0 showed better DFS (hazard ratio [HR], 0.86; 95% CI, 0.76-0.97) in the overall population and more favorable DFS (HR, 0.78; 95% CI, 0.64-0.95) and overall survival (HR, 0.65; 95% CI, 0.46-0.93) in the TN subgroup. Luminal A-like tumors in HER2-low (p = .014) and TN and luminal A-like in HER2-0 (p = .019) showed the worst DFS., Conclusions: In young patients with HER2-negative BC and germline BRCA1/2 PVs, HER2-low disease was less frequent than expected and more frequently linked to BRCA2 PVs and associated with luminal-like disease. HER2-low status was associated with a modestly improved prognosis., (© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Introduction: Triple negative breast cancer (TNBC) is a rare but aggressive biological subtype of breast cancer associated with higher locoregional and distant recurrence rates and lower overall survival despite advancements in diagnostic and treatment strategies., Areas Covered: This review explores the evolving landscape of locoregional recurrence (LRR) in TNBC with improved surgical and radiation therapy delivery techniques including salvage breast conserving surgery (SBCS), re-irradiation, and thermo-radiation. We review current retrospective and prospective, albeit limited, clinical data highlighting the optimal management of locoregionally recurrent TNBC. We also discuss tumor genomic profiling and transcriptome analysis and review potential investigational directions., Expert Opinion: Significant progress has been made in the prevention of LRR but rates remain suboptimal, particularly in the TNBC population, and outcomes following LRR are poor. Further prospective studies are needed to identify the most effective and safest systemic therapy regimens and to whom it should be offered. There has been growing interest in the role of molecular markers, genomic signatures, and tumor microenvironment in predicting outcomes and guiding LRR treatment. Transcriptome analyses and biomarker-driven investigations are currently being studied and represent a promising era of development in the management of LRR.

BACKGROUND Breast cancer is the most common malignancy in women worldwide. Despite treatment, recurrence and metastasis are common. Lobular breast cancer most commonly metastasizes to the lungs, liver, lymph nodes, and sites in the brain. Metastasis to the gastrointestinal tract is rare, with few cases reported to date. CASE REPORT This report describes a patient with late colon and gastric metastases from lobular breast cancer mimicking primary colon and gastric cancers. CONCLUSIONS Immunohistochemical methods can help differentiate metastatic breast disease to the gastrointestinal tract from primary gastrointestinal malignancy.