Tumor Mutational Landscape and Its Correlation With Histopathological Characteristics in Breast Cancer.
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Papadopoulou Eirini, Stathoulopoulou Maroulio, Matiatou Maria, Karathanasis Panagiotis, Xenakis Xenofon, Pesmatzoglou Grigorios, Fyssas Ioannis, Louis Konstantinos, Maniatis Dimitrios, Ekmektzoglou Anastasia, Alexandrou Dimitrios, Kalivopoulos Christos, Kanistras Christos, Katsiakis Nikolaos, Konstantiadou Ioanna, Kavazis Christos, Kokolakis Athanasios, Papaioannou Nikolaos, Sachoulidou Anna, Sfakianakis Eleftherios, Triantafyllidou Sofia, Filippidou Sofia, Damaskos Christos, Lazaridis George, Koinis Filippos, Biziota Eirini, Koutras Angelos, Kotsori Aikaterini, Venizelos Vassileios
Аннотация
MATERIALS AND METHODS: 227 breast cancer patients referred to Genekor's laboratory for tumor molecular profile analysis were included in the study. Pathology records were used to assess critical clinicopathological features, including HER2, ER, PR, Ki67, grade, metastatic site, and age. A 1021-gene NGS-based multigene panel was utilized to assess tumor biology alongside tumor mutational burden (TMB) and microsatellite instability (MSI).
RESULTS: Comprehensive genomic profiling revealed that 95.6% of the patients harbored at least one oncogenic or likely oncogenic alteration, highlighting the high diagnostic yield of NGS-based testing. Distinct subtype-specific patterns were observed: HR+/HER2- tumors were enriched for PIK3CA and ESR1 gene alterations, whereas triple-negative breast cancer (TNBC) was dominated by TP53 alterations. Clinically actionable alterations were most common in HR+/HER2- tumors (~60% on-label), whereas TNBC more often harbored off-label or trial-associated targets. The inclusion of tumor-agnostic biomarkers (TMB/MSI) increased on-label actionability up to 64.5% in HR+/HER2- tumors, primarily driven by TMB-high cases. Median TMB values were low, and age was the only independent predictor. Furthermore, the presence of actionable alterations was significantly higher in metastatic tumors, and TP53 alterations were associated with aggressive tumor characteristics.
CONCLUSION: Comprehensive NGS-based genomic profiling identifies clinically actionable alterations in over half of breast cancer patients, with substantial variability across molecular subtypes. The HR+/HER2- subtype demonstrates the highest prevalence of on-label actionable biomarkers. These findings support the routine implementation of comprehensive genomic profiling, especially in metastatic HER2-negative breast cancer, to guide precision oncology strategies and enable enrollment in biomarker-driven clinical trials.