HER-2 expression

In addition, we highlight the importance of molecular stratification and biomarker-driven approaches to identify patients most likely to benefit from anti-angiogenic therapy. Overall, while VEGFR-targeted therapy alone has shown limited success, rational combination strategies and improved patient selection may significantly enhance its clinical utility in TNBC.

Specifically, tumors with HER2 2+ expression exhibited a smaller median diameter, while the classic histological subtype was predominantly observed in HER2 0/1+ tumors. These associations indicate that differential HER2 expression may delineate distinct pathological phenotypes of bladder urothelial carcinoma.

Concurrently, dysregulated signaling, such as the Wnt/β-catenin pathway, inhibits dendritic cell maturation and recruits Myeloid-Derived Suppressor Cells (MDSCs) and regulatory T cells (Tregs) into the tumor microenvironment, thereby blunting the anti-tumor T cell response. This review examines the role of key pluripotency regulators in TNBC-mediated immune evasion, highlighting emerging immunotherapeutic strategies targeting these networks and summarizing current clinical research.

Future directions emphasize next-generation ICIs, optimized combination regimens, and AI-driven biomarker integration to achieve durable, personalized treatments. This review underscores the potential of immunotherapy to redefine TNBC management while highlighting the imperative for continued innovation to address unmet clinical needs.

The use of antibody-drug conjugates (ADCs) specific to human epidermal growth factor receptor 2 (HER2), such as ado-trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (Enhertu, T-DXd), and trastuzumab duocarmazine (SYD985), to treat breast cancer patients has been associated with a variety of toxicities including corneal epithelial keratitis. Incubation of normal human corneal epithelial cell lines with trastuzumab or T-DXd demonstrated the capacity for receptor-mediated endocytosis of HER2-targeted therapies by epithelia in the eye. Our findings of HER2 expression in normal human corneal epithelium suggest that the ocular adverse events associated with HER2-targeted ADCs may be driven, at least in part, by an on-target effect.

P=N/A, N=10, Recruiting, Emory University | Trial completion date: Apr 2027 --> Feb 2028 | Trial primary completion date: Apr 2026 --> Feb 2027

Mirvetuximab soravtansine (MIRV), which targets folate receptor-1 (FOLR1), is FDA-approved for platinum-resistant tubo-ovarian cancers with ≥75% moderate/strong staining, and emerging studies show meaningful responses to MIRV combination therapy even at lower FOLR1 expression. FOLR1 met current MIRV treatment criteria in one case, while ten others showed expression ranging from 5% to 70%. Although most tumors did not meet current biomarker thresholds for Trastuzumab or MIRV monotherapy, detectable expression supports exploring anti-HER2 T-Dxd and MIRV combination treatments in selected MA/MLA cases.

This approach has the potential to detect low HER2 expression in less invasive samples. However, validation through larger-scale clinical trials should be considered to achieve more efficiency.

Heterogeneity in ER, PR, HER2, and molecular subtype expression significantly influences prognosis and treatment outcomes in metastatic breast cancer. Reassessment of receptor status in metastatic lesions is essential for optimizing individualized treatment strategies and improving patient outcomes.

In summary, our study establishes the comprehensive molecular atlas and a targeted therapeutic subtyping framework, revealing therapeutic vulnerabilities and providing novel insights for advancing precision oncology in OCCC management.

 MBC in this cohort presented with aggressive histopathological features and predominantly advanced-stage disease. These findings highlight the need for improved breast cancer awareness, early detection, and individualized treatment strategies, particularly in resource-limited settings.

While MAPK pathway inhibitors show limited efficacy in monotherapy, preclinical and clinical data suggest that their integration with existing treatment strategies may enhance therapeutic robustness, delay resistance and reduce recurrence. Targeting MAPK, in combination with other drugs that restrain CSC plasticity could represent a promising strategy to improve long-term outcomes in TNBC.