PIK3CA N345K

However, clinical trials have been predominantly carried out with selected populations and single drugs (Palbociclib, Ribociclib or Abemaciclib). At baseline, and considering the pre-defined criteria, ctDNA analysis detected PIK3CA mutations in 32.25% and 44.44% of patients by AVENIO and ddPCR, respectively. ESR1 mutations were detected in 3.22% and 9.37% by AVENIO and ddPCR, respectively. For PIK3CA mutations, the Kappa value was 0.62 (p-value: 0.0004) and 0.47 for ESR1 mutations (p-value: 0.0039).

P2, N=51, Recruiting, GOG Foundation | Not yet recruiting --> Recruiting

PIK3CA is among the most frequently mutated genes in BC (approximately 40% of cases) and its mutations portend sensitivity to PI3K inhibitors, such as alpelisib, in combination with hormonal treatment in HR+/HER2- cases... In our analysis PIK3CA was confirmed to be the most frequently mutated gene (51% of cases); however, due to the specific European regulatory constraints, it was deemed to be actionable in a minority of cases, suggesting that NGS profiling should be performed early on after the diagnosis of metastatic disease, in order to inform the overall therapeutic strategy. Other potentially actionable alterations (FGFR1/2, AKT, HER2 ex 20 mutations) emerged from extended NGS profiling, suggesting its potential utility in selected HR+/HER2- mBC pts.

However, intriguingly, ResolveOME™ uncovered cells of stem-like identity harboring PIK3CA missense mutations as well as uncovered cells still formally identified as epithelial and harboring mutant PIK3CA but with differential expression profiles—indicative of cells morphing cell state. Finally, the TotalSeq™ antibody panel unveiled intercellular heterogeneity and interpatient heterogeneity both in cell-surface protein phenotype of immune cells and in epithelial identity and signaling.This ongoing study continues to catalog the three omic layers in increasing numbers of single cells and significantly expanding targeted surface-protein analysis harnessing the power of the single-cell united data to determine the “penetrance” of genomic changes in the context of cognate transcript and protein information, with the ultimate goals of defining DCIS to IDC transition factors as well as novel biomarker identification that may be exploited therapeutically.

We identified pts with EGFR mutations or ALK rearrangements who developed PIK3CA/PTEN alterations in tissue biopsy and/or circulating tumor DNA upon progression to first-line osimertinib/alectinib. Activating PI3KCA mutations and molecular events leading to PTEN loss are frequent events at resistance to first-line EGFR/ALK TKIs, and can be detected concomitantly. Functional assays confirmed that these alterations act as resistance mechanisms. These observations are of interest as PI3KCA/mTOR inhibitors may have a role in overcoming resistance.

Taken together, our work provided a comprehensive analysis of driver and targetable alterations in SBA, which can facilitate the practice of precision oncology in this challenging disease.

In this group of HR/HER2 breast cancer patients, common PIK3CA gene mutations account for the vast majority of the mutations. New rare variants in PIK3CA are also identified while their clinical significance needs to be further studied in a large cohort and/or multi-center study.

For germline BRCA1-mutated breast cancer, TP53 R175H was unanimously the most frequent mutation among the three germline cohorts. Our study provides lists of potential shared neoantigens among BRCA1-related breast cancer, which may be used in developing off-the-shelf neoantigen-based vaccines.

P2, N=51, Not yet recruiting, GOG Foundation | Trial completion date: Apr 2025 --> Apr 2026 | Initiation date: Apr 2022 --> Jan 2023 | Trial primary completion date: Aug 2024 --> Apr 2025

P2, N=11, Completed, NRG Oncology | Active, not recruiting --> Completed

P2, N=51, Not yet recruiting, GOG Foundation