{"entity":{"id":"paper-park-hrd-pancreatic-platinum-ccr-2020","kind":"paper","name":"Genomic methods identify homologous recombination deficiency in pancreas adenocarcinoma and optimize treatment selection","aka":[],"tldr":"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.","summary":"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.","asOf":"2026-09-24","links":[{"label":"Park et al., Clin Cancer Res 2020: homologous recombination deficiency in 262 advanced patients and first-line platinum","url":"https://doi.org/10.1158/1078-0432.CCR-20-0418"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32444418/"}],"tags":[],"related":["hrd-positive","brca-somatic","brca-germline"],"cancers":["pancreatic","brca-palb2-pdac","metastatic-pdac"],"sections":[],"technologies":["hrd-testing"],"targets":["brca","palb2","atm"],"drugs":["folfirinox","gemcitabine-cisplatin"],"companies":[],"institutions":["mskcc"],"pathways":["homologous-recombination-repair"],"terms":["hrd","germline-vs-somatic","mutational-signature"],"trials":[],"people":["eileen-oreilly","vinod-balachandran"],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2020,"doi":"10.1158/1078-0432.CCR-20-0418","pmid":"32444418","authors":"Park W, Chen J, Chou JF, et al.","paperType":"observational","findings":["Homologous recombination gene mutation in 19%: germline 15%, somatic 4%; biallelic 11%, core 12%.","First-line platinum progression-free survival hazard ratio 0.44 in the deficient group; no benefit from non-platinum.","Core and biallelic mutations carry the higher genomic instability and the larger benefit."],"whatItMeans":"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.","caveats":["Retrospective single-centre series; treatment not randomised.","Non-core genes such as ATM showed little benefit but small numbers."],"changedPractice":false,"participants":262},"route":"/key-papers/paper-park-hrd-pancreatic-platinum-ccr-2020/","neighbours":{"biomarker":[{"id":"brca-germline","kind":"biomarker","name":"Germline BRCA1/2 pathogenic variant (gBRCAm)","route":"/biomarkers/brca-germline/"},{"id":"hrd-positive","kind":"biomarker","name":"HRD-positive (genomic instability score)","route":"/biomarkers/hrd-positive/"},{"id":"brca-somatic","kind":"biomarker","name":"Tumour (somatic or germline) BRCA1/2 mutation and HRR gene alterations","route":"/biomarkers/brca-somatic/"}],"cancer":[{"id":"brca-palb2-pdac","kind":"cancer","name":"BRCA or PALB2-mutant pancreatic ductal adenocarcinoma","route":"/cancers/brca-palb2-pdac/"},{"id":"metastatic-pdac","kind":"cancer","name":"Metastatic pancreatic ductal adenocarcinoma","route":"/cancers/metastatic-pdac/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"technology":[{"id":"hrd-testing","kind":"technology","name":"HRD & BRCA testing","route":"/technologies/hrd-testing/"}],"target":[{"id":"atm","kind":"target","name":"ATM","route":"/targets/atm/"},{"id":"brca","kind":"target","name":"BRCA1 / BRCA2 (HRD)","route":"/targets/brca/"},{"id":"palb2","kind":"target","name":"PALB2","route":"/targets/palb2/"}],"drug":[{"id":"folfirinox","kind":"drug","name":"FOLFIRINOX / mFOLFIRINOX","route":"/drugs/folfirinox/"},{"id":"gemcitabine-cisplatin","kind":"drug","name":"Gemcitabine + cisplatin","route":"/drugs/gemcitabine-cisplatin/"}],"institution":[{"id":"mskcc","kind":"institution","name":"Memorial Sloan Kettering Cancer Center","route":"/institutions/mskcc/"}],"pathway":[{"id":"homologous-recombination-repair","kind":"pathway","name":"Double-strand break repair: HR versus end joining","route":"/pathways/homologous-recombination-repair/"}],"term":[{"id":"germline-vs-somatic","kind":"term","name":"Germline vs somatic mutations","route":"/terms/germline-vs-somatic/"},{"id":"hrd","kind":"term","name":"Homologous recombination deficiency (HRD)","route":"/terms/hrd/"},{"id":"mutational-signature","kind":"term","name":"Mutational signature","route":"/terms/mutational-signature/"}],"person":[{"id":"eileen-oreilly","kind":"person","name":"Eileen M. O'Reilly","route":"/people/eileen-oreilly/"},{"id":"vinod-balachandran","kind":"person","name":"Vinod P. Balachandran","route":"/people/vinod-balachandran/"}],"journal":[{"id":"clinical-cancer-research","kind":"journal","name":"Clinical Cancer Research","route":"/journals/clinical-cancer-research/"}],"trial":[{"id":"polo","kind":"trial","name":"POLO","route":"/trials/polo/"}]}}