{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T08:54:35Z","timestamp":1793350475186,"version":"4.5.0"},"reference-count":16,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"8","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2026,3,10]]},"abstract":"\n PURPOSE<\/jats:title>\n \n Translational Breast Cancer Research Consortium 048 was a proof-of-principle trial demonstrating responses to the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib in patients (pts) with metastatic breast cancer (MBC) with germline (g)\n PALB2<\/jats:italic>\n or somatic (s)\n BRCA<\/jats:italic>\n mutations (s\n BRCA<\/jats:italic>\n m). Here we report results from the expansion cohorts in a larger sample of pts with g\n PALB2<\/jats:italic>\n m or s\n BRCA<\/jats:italic>\n m.\n <\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n \n Eligible pts had MBC of any subtype with measurable disease and a g\n PALB2<\/jats:italic>\n m or s\n BRCA<\/jats:italic>\n m. Pts received olaparib 300 mg twice a day until progression. The primary end point was overall response rate. Secondary end points include clinical benefit rate (CBR) at 18 weeks, progression-free survival (PFS), duration of response (DOR), and whether among s\n BRCA<\/jats:italic>\n m carriers the mutant allele frequency (MAF) is significantly higher in responders than in nonresponders.\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n Fifty-four pts with g\n PALB2<\/jats:italic>\n m (N = 24) or s\n BRCA<\/jats:italic>\n m (N = 30) were enrolled. Forty-two (78%) had estrogen receptor\u2013positive human epidermal growth factor receptor 2\u2013negative (HER2\u2013) MBC, seven (13%) had triple-negative breast cancer, and five (9%) had HER2+ disease. Among pts with a g\n PALB2<\/jats:italic>\n m, the overall response rate (ORR) was 75% (80% CI, 60.2 to 86.3), CBR was 83.3% (90% CI, 65.8 to 94.1), the median PFS was 9.4 months (90% CI, 8.3 to 13.1), and the median DOR was 7.0 months (90% CI, 5.6 to 10.4). Among pts with s\n BRCA<\/jats:italic>\n m (15 s\n BRCA1<\/jats:italic>\n and 15 s\n BRCA2<\/jats:italic>\n ), the ORR was 36.7% (80% CI, 24.7 to 50), CBR was 53.3% (90% CI, 37 to 69.1), the median PFS was 5.5 months (90% CI, 2.8 to 8.3), and the median DOR was 11.2 months (90% CI, 4.4 to not reached). One additional pt had an unconfirmed partial response. Although clinically meaningful, the ORR in pts with s\n BRCA<\/jats:italic>\n m did not achieve the prespecified target. Among s\n BRCA<\/jats:italic>\n m carriers, the mean MAF did not differ significantly between responders (46%) and nonresponders (39%;\n P<\/jats:italic>\n = .7).\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSION<\/jats:title>\n \n Olaparib is active in pts with MBC with g\n PALB2<\/jats:italic>\n m and s\n BRCA<\/jats:italic>\n m, significantly expanding the population of pts with breast cancer likely to benefit from PARP inhibitors beyond g\n BRCA1\/2<\/jats:italic>\n m carriers.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1200\/jco-25-02075","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T20:59:30Z","timestamp":1769633970000},"page":"653-661","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":15,"title":["TBCRC 048 (Olaparib Expanded) Expansion Cohorts: Phase II Study of Olaparib Monotherapy for Patients With Metastatic Breast Cancer With Germline Mutations in\n PALB2<\/i>\n or Somatic Mutations in\n BRCA1<\/i>\n or\n BRCA2<\/i>"],"prefix":"10.1200","volume":"44","clinical-trial-number":[{"clinical-trial-number":"nct03344965","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1422-3734","authenticated-orcid":true,"given":"Nadine M.","family":"Tung","sequence":"first","affiliation":[{"name":"Beth Israel Deaconess Medical Center, Boston, MA"},{"name":"Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3109-1692","authenticated-orcid":true,"given":"Mark E.","family":"Robson","sequence":"additional","affiliation":[{"name":"Memorial Sloan-Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyu","family":"Li","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5248-0876","authenticated-orcid":true,"given":"Rita","family":"Nanda","sequence":"additional","affiliation":[{"name":"The University of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5874-3390","authenticated-orcid":true,"given":"Payal D.","family":"Shah","sequence":"additional","affiliation":[{"name":"Basser Center for BRCA, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3899-8649","authenticated-orcid":true,"given":"Katia","family":"Khoury","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham, Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7096-9624","authenticated-orcid":true,"given":"Gretchen","family":"Kimmick","sequence":"additional","affiliation":[{"name":"Duke University Medical Center, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0979-8787","authenticated-orcid":true,"given":"Cesar","family":"Santa-Maria","sequence":"additional","affiliation":[{"name":"Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8080-7960","authenticated-orcid":true,"given":"Adam","family":"Brufsky","sequence":"additional","affiliation":[{"name":"Division of Hematology Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"DeMeo","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joao Pedro","family":"Vieira","sequence":"additional","affiliation":[{"name":"Beth Israel Deaconess Medical Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2388-4649","authenticated-orcid":true,"given":"Lisa A.","family":"Carey","sequence":"additional","affiliation":[{"name":"University of North Carolina, Chapel Hill, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7868-6231","authenticated-orcid":true,"given":"Gerburg","family":"Wulf","sequence":"additional","affiliation":[{"name":"Beth Israel Deaconess Medical Center, Boston, MA"},{"name":"Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5914-7272","authenticated-orcid":true,"given":"Susan","family":"Domchek","sequence":"additional","affiliation":[{"name":"Basser Center for BRCA, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6380-5944","authenticated-orcid":true,"given":"Ian E.","family":"Krop","sequence":"additional","affiliation":[{"name":"Yale Cancer Center, Newhaven, VT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3734-1063","authenticated-orcid":true,"given":"Antonio C.","family":"Wolff","sequence":"additional","affiliation":[{"name":"Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8819-1723","authenticated-orcid":true,"given":"Eric P.","family":"Winer","sequence":"additional","affiliation":[{"name":"Yale Cancer Center, Newhaven, VT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9449-3982","authenticated-orcid":true,"given":"Judy E.","family":"Garber","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA"},{"name":"Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the Translational Breast Cancer Research Consortium (TBCRC)","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_10_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1706450"},{"key":"e_1_3_10_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1802905"},{"key":"e_1_3_10_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2105215"},{"key":"e_1_3_10_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2022.09.159"},{"key":"e_1_3_10_6_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.02151"},{"key":"e_1_3_10_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdz012"},{"key":"e_1_3_10_8_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2019.37.15_suppl.3006"},{"key":"e_1_3_10_9_2","volume-title":"National Comprehensive Cancer Network Clinical Practice Guidelines in Breast Cancer. Version 4.2025","unstructured":"National Comprehensive Cancer Network Clinical Practice Guidelines in Breast Cancer. Version 4.2025. https:\/\/www.nccn.org"},{"key":"e_1_3_10_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3934"},{"key":"e_1_3_10_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature17676"},{"key":"e_1_3_10_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4292"},{"key":"e_1_3_10_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2020.04.035"},{"key":"e_1_3_10_14_2","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201809172"},{"key":"e_1_3_10_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdy099"},{"key":"e_1_3_10_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.02.008"},{"key":"e_1_3_10_17_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.01907"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO-25-02075","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T22:59:21Z","timestamp":1772751561000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO-25-02075"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,10]]},"references-count":16,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,3,10]]}},"alternative-id":["10.1200\/JCO-25-02075"],"URL":"https:\/\/doi.org\/10.1200\/jco-25-02075","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,10]]},"assertion":[{"value":"2025-08-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-06","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}