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Multi-Omics Insights Driving Personalized Therapy in Metastatic Triple-Negative Breast Cancer (TNBC)

Patient: 55 years – Female with metastatic triple-negative breast carcinoma (ER–, PR–, HER2 1+)

Clinical Testing:
Alterations: TP53 (p.D281E), MSH3 (p.R454*), PIK3CA (p.E542K), SMAD4 (p.E307*), SMARCA4 (p.D1127H), NF2 (p.E335*), CD274 (PD-L1, RNA)
Genes: TP53, MSH3, PIK3CA, SMAD4, SMARCA4, NF2, CD274
Treatment Options: PI3K/AKT/mTOR pathway inhibitors (Alpelisib, Everolimus, Temsirolimus), immunotherapy guided by PD-L1 expression, consideration of PARP inhibitors for intermediate HRD status, and clinical trials targeting genomic instability or resistance pathways.
Indication: Metastatic recurrent triple-negative breast carcinoma (TNBC)
Research Findings: Multi-omic profiling from both tissue and plasma revealed pathogenic somatic variants driving tumor heterogeneity and resistance. Intermediate HRD and PD-L1 expression suggest potential responsiveness to PARP inhibition and immunotherapy. Longitudinal NGS provided insights into molecular evolution, informing precision treatment strategies and prognostic assessment

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