ReviewClinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico2026
Redefining breast cancer: therapeutic opportunities in HER2-low and emerging molecular subtypes.
Review in Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Authors and funding
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Abstract
Breast cancer classification has undergone significant evolution; however, the long-standing binary model distinguishing HER2-positive from HER2-negative disease is now recognized as overly simplistic and clinically limiting. Emerging evidence supports the identification of HER2-low (IHC 1 + or 2 + /ISH -) as a biologically heterogeneous and therapeutically actionable subgroup within the continuum of HER2 expression. This review synthesizes current advances in the understanding of HER2-low disease, with particular emphasis on its molecular characteristics, diagnostic challenges, and therapeutic implications in the era of precision oncology. The clinical relevance of HER2-low tumors has been propelled by the development of next-generation antibody-drug conjugates (ADCs), most notably trastuzumab deruxtecan, which has demonstrated robust survival benefits in patients previously classified as HER2-negative. These agents leverage low antigen expression through improved linker stability, high drug-to-antibody ratios, and a potent bystander effect, thereby expanding the scope of HER2-targeted therapy. In parallel, accumulating data reveal substantial biological complexity in HER2-low tumors, including variable hormone receptor co-expression, distinct genomic and transcriptomic signatures, and dynamic tumor microenvironment interactions. Key limitations such as inter-observer variability in HER2 assessment, intratumoral heterogeneity, and emerging resistance mechanisms-driven by drug efflux transporters and clonal evolution-are also critically examined. Furthermore, advances in liquid biopsy, artificial intelligence-assisted pathology, and multi-omics integration are redefining tumor stratification beyond static HER2 categorization. Overall, this review highlights HER2-low as a paradigm-shifting entity and underscores the need to harmonize diagnostic precision with innovative therapeutic strategies to optimize clinical outcomes.
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42481820What Socratic holds
Registered trials
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