International Conference on Vascular Anomalies: Translating basic research into new therapies (VAC 2025)! :
Exciting program, including novel preclinical models, drugs, and most recent results from clinical trials! lnkd.in/e6_BbzQF. Registrations: lnkd.in/dzTfFVej
#VASCAPA, #HEVAS, #CMTC
#EVBO, #ISSVA #angiogenesis #PIK3CA #TIE2 #KRAS
Moving from the simplistic definition of #ESR1 and #PIK3CA mutated metastatic #BreastCancer to a more granular resolution of single codon variants thanks to #ctDNA and #LiquidBiopsy for a more precise biological and clinical profiling of #MBC
https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-023-01718-0
Background although being central for the biology and druggability of hormone-receptor positive, HER2 negative metastatic breast cancer (MBC), ESR1 and PIK3CA mutations are simplistically dichotomized as mutated or wild type in current clinical practice. Methods The study analyzed a multi-institutional cohort comprising 703 patients with luminal-like MBC characterized for circulating tumor DNA through next generation sequencing (NGS). Pathway classification was defined based on previous work (i.e., RTK, RAS, RAF, MEK, NRF2, ER, WNT, MYC, P53, cell cycle, notch, PI3K). Single nucleotide variations (SNVs) were annotated for their oncogenicity through OncoKB. Only pathogenic variants were included in the models. Associations among clinical characteristics, pathway classification, and ESR1/PIK3CA codon variants were explored. Results The results showed a differential pattern of associations for ESR1 and PIK3CA codon variants in terms of co-occurring pathway alterations patterns of metastatic dissemination, and prognosis. ESR1 537 was associated with SNVs in the ER and RAF pathways, CNVs in the MYC pathway and bone metastases, while ESR1 538 with SNVs in the cell cycle pathway and liver metastases. PIK3CA 1047 and 542 were associated with CNVs in the PI3K pathway and with bone metastases. Conclusions The study demonstrated how ESR1 and PIK3CA codon variants, together with alterations in specific oncogenic pathways, can differentially impact the biology and clinical phenotype of luminal-like MBC. As novel endocrine therapy agents such as selective estrogen receptor degraders (SERDS) and PI3K inhibitors are being developed, these results highlight the pivotal role of ctDNA NGS to describe tumor evolution and optimize clinical decision making.
Miikka Vikkula
Lorenzo Gerratana
am730