What matters more in BRCA? TYPE vs LOCATION of the variant
What matters more in BRCA? TYPE vs LOCATION of the variant 🧬🤔 🧬 Key Findings Protein-truncating BRCA1 variants = WORSE OS HR 2.00 vs non-truncating ❗ Missense = BEST prognosis ✨ • BRCA1 missense → HR 0.48 • BRCA2 missense → HR 0.17 📍 Exon location matters • BRCA1 exon 2 & exon 10 → worse OS • BRCA2 exon 10 → earlier diagnosis (<30y) • BRCA2 exons 15–26 → worse DFS 📉 🚫 No major impact on: Tumour phenotype, baseline clinico-pathologic features, and DFS (for most variant groups) 🔍 Variant categories analysed Frameshift, nonsense, missense, splicing, CNVs, indels, SNVs + exon-wise & domain-wise mapping 🗺️ 🌍 Study scale • 5660 screened → 3294 analysed • 2080 BRCA1, 1214 BRCA2 • Median follow-up ~8 years • Trial: NCT03673306 💡 Takeaway Not all BRCA mutations behave the same. Predicted functional consequence > variant type. Missense = favourable biology ✨ Truncating & certain exon hotspots = higher risk ⚠️ Future → Variant-specific management in hereditary breast cancer. 🎯 #OncoTwitter #MedTwitter #BreastCancer #BRCA #CancerGenomics
