{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T10:11:47Z","timestamp":1756894307422,"version":"3.41.2"},"reference-count":17,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"9","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2025,4]]},"abstract":"\n PURPOSE<\/jats:title>\n \n The PENELOPE-B trial (ClinicalTrials.gov identifier:\n NCT01864746<\/jats:ext-link>\n ) recruited patients with hormone receptor+\/human epidermal growth factor receptor 2\u2013 early breast cancer without a pathological complete response after taxane-containing neoadjuvant chemotherapy and at a high risk of relapse. Patients were randomly assigned (1:1) to receive 13 cycles of palbociclib once daily or placebo on days 1-21 in a 28-day cycle in addition to endocrine therapy (ET). PENELOPE-B did not show improved invasive disease-free survival (iDFS) after adding palbociclib to ET. This retrospective analysis investigated the impact of germline pathogenic variant (PV) status of\n BRCA1\/2<\/jats:italic>\n and non-\n BRCA1\/2<\/jats:italic>\n cancer predisposition genes on the outcomes of PENELOPE-B trial patients.\n <\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n In total, 445 patients were sampled following a case-cohort design and 442 were analyzed for germline PVs. Statistical analyses were performed for time-to-event end points (iDFS, distant disease-free survival [DDFS], and overall survival [OS]).<\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n Of the 442 patients, 42 carried PVs in any cancer predisposition gene; 15 carried\n BRCA1\/2<\/jats:italic>\n PVs. Irrespective of the treatment arms, PV status was not a prognostic factor. Regarding the treatment arms in\n BRCA1\/2<\/jats:italic>\n PV carriers, numerically better 3-year outcomes were observed in the palbociclib arm (iDFS, 95%; DDFS, 95%; OS, 100%) than in the placebo arm (iDFS, 72.8%; DDFS, 72.8%; OS, 87.5%; hazard ratios palbociclib\n v<\/jats:italic>\n placebo 0.349 [iDFS] and 0.562 [DDFS], not calculated for OS, too few events). In patients without\n BRCA1\/2<\/jats:italic>\n PVs, the differences in 3-year outcomes were negligible. PVs in non-\n BRCA1\/2<\/jats:italic>\n cancer predisposition genes did not influence the efficacy of palbociclib, although gene-specific effects could not be excluded.\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSION<\/jats:title>\n \n Patients with\n BRCA1\/2<\/jats:italic>\n PVs had numerically better outcomes after palbociclib. However, the number of\n BRCA1\/2<\/jats:italic>\n carriers was small. Larger randomized clinical trials should consider the PV status to further evaluate whether\n BRCA1\/2<\/jats:italic>\n PV carriers benefit from cyclin-dependent kinase 4 and 6 inhibitor treatment.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1200\/po-24-00742","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T19:59:11Z","timestamp":1744315151000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":1,"title":["BRCA1\/2<\/i>\n and Other Predisposition Genes in High-Risk Hormone Receptor+\/Human Epidermal Growth Factor Receptor 2\u2013 Breast Cancer Treated With Endocrine Therapy With or Without Palbociclib: A Secondary PENELOPE-B Study Analysis"],"prefix":"10.1200","clinical-trial-number":[{"clinical-trial-number":"nct01864746","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1152-8367","authenticated-orcid":true,"given":"Eric","family":"Hahnen","sequence":"first","affiliation":[{"name":"Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Faculty of Medicine, University Hospital Cologne, Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Hauke","sequence":"additional","affiliation":[{"name":"Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Faculty of Medicine, University Hospital Cologne, Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4111-2757","authenticated-orcid":true,"given":"Karen","family":"Gelmon","sequence":"additional","affiliation":[{"name":"BC Cancer, Vancouver, BC, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6591-3367","authenticated-orcid":true,"given":"Frederik","family":"Marm\u00e9","sequence":"additional","affiliation":[{"name":"Universit\u00e4tsfrauenklinik Mannheim, Mannheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7756-8815","authenticated-orcid":true,"given":"Corinna","family":"Ernst","sequence":"additional","affiliation":[{"name":"Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Faculty of Medicine, University Hospital Cologne, Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9237-3231","authenticated-orcid":true,"given":"Miguel","family":"Martin","sequence":"additional","affiliation":[{"name":"Instituto de Investigacion Sanitaria Gregorio Mara\u00f1on, CIBERONC, Universidad Complutense, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1233-1267","authenticated-orcid":true,"given":"Michael","family":"Untch","sequence":"additional","affiliation":[{"name":"Helios Kliniken Berlin Buch, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herv\u00e9","family":"Bonnefoi","sequence":"additional","affiliation":[{"name":"Institut Bergoni\u00e9 and Universit\u00e9 de Bordeaux INSERM U916, Bordeaux, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5130-5969","authenticated-orcid":true,"given":"Erik","family":"Knudsen","sequence":"additional","affiliation":[{"name":"Roswell Park Comprehensive Cancer Center, Buffalo, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5396-6533","authenticated-orcid":true,"given":"Seock-Ah","family":"Im","sequence":"additional","affiliation":[{"name":"Seoul National University Hospital, Seoul, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1297-4251","authenticated-orcid":true,"given":"Angela","family":"DeMichele","sequence":"additional","affiliation":[{"name":"Penn Medicine Abramson Cancer Center, Philadelphia, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9838-8298","authenticated-orcid":true,"given":"Laura","family":"Van't Veer","sequence":"additional","affiliation":[{"name":"The University of California, San Francisco, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5588-8332","authenticated-orcid":true,"given":"Sung-Bae","family":"Kim","sequence":"additional","affiliation":[{"name":"Asan Medical Center, University of Ulsan College of Medicine, Seoul, 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