{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T19:56:55Z","timestamp":1793908615846,"version":"4.8.0"},"reference-count":30,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"3","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2026,3]]},"abstract":"\n PURPOSE<\/jats:title>\n \n Germline\n BRCA<\/jats:italic>\n (g\n BRCA<\/jats:italic>\n ) mutations confer increased sensitivity to platinum-based chemotherapy and have been associated with improved survival across several malignancies. This study investigated the effect of g\n BRCA<\/jats:italic>\n mutation status on the antitumor activity of modified fluorouracil, folinic acid, irinotecan, and oxaliplatin (FOLFIRINOX; mFFX) in patients with advanced pancreatic cancer (APC).\n <\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n \n This multicenter retrospective study was performed in 178 patients with histologically confirmed APC who received mFFX, comprising 17 g\n BRCA<\/jats:italic>\n -positive and 161 g\n BRCA<\/jats:italic>\n -negative individuals. Efficacy outcomes, including progression-free survival (PFS), objective response rate (ORR), and normalization rate of carbohydrate antigen 19-9 (CA19-9), were compared between groups using univariate and multivariate analyses.\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n Median PFS was significantly longer in g\n BRCA<\/jats:italic>\n -positive than in g\n BRCA<\/jats:italic>\n -negative patients (10.6\n v<\/jats:italic>\n 5.3 months,\n P<\/jats:italic>\n = .005). Independent predictors of PFS included g\n BRCA<\/jats:italic>\n mutation (hazard ratio [HR], 3.65), disease extent (HR, 2.34), and previous chemotherapy (HR, 1.66). g\n BRCA-<\/jats:italic>\n positive patients demonstrated a significantly higher ORR (82%\n v<\/jats:italic>\n 34%, odds ratio, 0.11,\n P<\/jats:italic>\n < .001) and CA19-9 normalization rate (69%\n v<\/jats:italic>\n 10%,\n P<\/jats:italic>\n < 0.01). ORR was associated with g\n BRCA<\/jats:italic>\n status (HR, 0.04), disease extent (HR, 0.11), and treatment history (HR, 0.27). Among 68 responders, sustained shrinkage of both primary and metastatic tumors and continued CA19-9 decline were observed during the first 6 months in g\n BRCA-<\/jats:italic>\n positive patients, whereas responses in g\n BRCA<\/jats:italic>\n -negative patients plateaued after 3 months. Subgroup analysis revealed that most patient subgroups demonstrated superior PFS and ORR in the g\n BRCA<\/jats:italic>\n -positive cohort compared with those in the g\n BRCA<\/jats:italic>\n -negative cohort.\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSION<\/jats:title>\n \n g\n BRCA<\/jats:italic>\n mutation status was strongly associated with enhanced radiologic and biological responses to mFFX in APC. Routine screening for g\n BRCA<\/jats:italic>\n mutations may provide essential guidance in therapeutic decision making and substantially improve clinical outcomes in this population.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1200\/po-25-01104","type":"journal-article","created":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T20:59:07Z","timestamp":1772744347000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Impact of Germline\n BRCA<\/i>\n Mutation Status on Antitumor Activity of Modified FOLFIRINOX in Patients With Advanced Pancreatic Cancer: An Exploratory Analysis"],"prefix":"10.1200","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1005-5606","authenticated-orcid":true,"given":"Lingaku","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Hepato-Biliary-Pancreatology, NHO Kyushu Cancer Center, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Tachibana","sequence":"additional","affiliation":[{"name":"Department of Hepato-Biliary-Pancreatic Medicine, Saiseikai Fukuoka General Hospital, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susumu","family":"Matsuo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, NHO Fukuoka Higashi Medical Center, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Niina","sequence":"additional","affiliation":[{"name":"Department of Hepato-Biliary-Pancreatology, NHO Kyushu Cancer Center, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0496-7684","authenticated-orcid":true,"given":"Takashi","family":"Fujiyama","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, NHO Fukuoka Higashi Medical Center, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4965-086X","authenticated-orcid":true,"given":"Terumasa","family":"Hisano","sequence":"additional","affiliation":[{"name":"Department of Hepato-Biliary-Pancreatology, NHO Kyushu Cancer Center, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3906-9307","authenticated-orcid":true,"given":"Rie","family":"Sugimoto","sequence":"additional","affiliation":[{"name":"Department of Hepato-Biliary-Pancreatology, NHO Kyushu Cancer Center, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3788-6787","authenticated-orcid":true,"given":"Tetsuro","family":"Akashi","sequence":"additional","affiliation":[{"name":"Department of Hepato-Biliary-Pancreatic Medicine, Saiseikai Fukuoka General Hospital, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiichiro","family":"Ogoshi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, NHO Fukuoka Higashi Medical Center, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1278-0775","authenticated-orcid":true,"given":"Masayuki","family":"Furukawa","sequence":"additional","affiliation":[{"name":"Department of Hepato-Biliary-Pancreatology, NHO Kyushu Cancer Center, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_7_2_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-14-0155"},{"key":"e_1_3_7_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1304369"},{"key":"e_1_3_7_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1011923"},{"key":"e_1_3_7_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1457"},{"key":"e_1_3_7_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1431"},{"key":"e_1_3_7_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-024-02834-0"},{"key":"e_1_3_7_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-024-02173-0"},{"key":"e_1_3_7_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-019-0582-7"},{"key":"e_1_3_7_10_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-20-0418"},{"key":"e_1_3_7_11_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.01890"},{"key":"e_1_3_7_12_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-0224"},{"key":"e_1_3_7_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1903387"},{"key":"e_1_3_7_14_2","first-page":"603","article-title":"NCCN guidelines updates: Pancreatic cancer","volume":"17","author":"Tempero MA","year":"2019","unstructured":"Tempero MA: NCCN guidelines updates: Pancreatic cancer. 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