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In 262 patients with advanced pancreatic cancer, the 19% with a broken homologous recombination gene did much better on first-line platinum chemotherapy than others, and the benefit was concentrated in BRCA1, BRCA2 and PALB2 and in tumours that had lost both copies.
Progression-free and overall survival were evaluated in advanced pancreatic ductal adenocarcinoma patients with both germline and somatic targeted sequencing. Homologous recombination mutations (17 genes) were grouped as germline versus somatic, core (BRCA1, BRCA2, PALB2) versus non-core, and monoallelic versus biallelic; genomic instability was compared by large-scale state transitions, signature 3 and tumour mutation burden. Among 262 patients, 50 (19%) had deficiency (15% germline, 4% somatic). Median overall and progression-free survival were 15.5 and 7 months. Deficient patients had improved progression-free survival on first-line platinum (hazard ratio 0.44) but not non-platinum. Biallelic (11%) and core (12%) mutations had higher genomic instability and greater platinum benefit.
It defines who a homologous recombination result should send to platinum: core-gene and biallelic carriers, germline or somatic, rather than any repair-gene variant.
Shares Tumour (somatic or germline) BRCA1/2 mutation and HRR gene alterations, ATM, PALB2, Germline BRCA1/2 pathogenic variant (gBRCAm).
Shares HRD-positive (genomic instability score), Tumour (somatic or germline) BRCA1/2 mutation and HRR gene alterations, PALB2, HRD & BRCA testing.
Shares ATM, PALB2, Eileen M. O'Reilly, Germline BRCA1/2 pathogenic variant (gBRCAm).
Shares Tumour (somatic or germline) BRCA1/2 mutation and HRR gene alterations, PALB2, Germline BRCA1/2 pathogenic variant (gBRCAm), Germline vs somatic mutations.
Shares POLO, Germline BRCA1/2 pathogenic variant (gBRCAm), Gemcitabine + cisplatin, BRCA or PALB2-mutant pancreatic ductal adenocarcinoma.
Shares HRD-positive (genomic instability score), Tumour (somatic or germline) BRCA1/2 mutation and HRR gene alterations, HRD & BRCA testing, Mutational signature.
Shares ATM, PALB2, Germline BRCA1/2 pathogenic variant (gBRCAm), Germline vs somatic mutations.
Shares HRD-positive (genomic instability score), PALB2, HRD & BRCA testing, Mutational signature.