{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T17:03:12Z","timestamp":1781715792643,"version":"3.54.5"},"reference-count":38,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Germline BRCA1\/2-mutated (gBRCAm) hormone receptor-positive\/HER2-negative (HR+\/HER2-) metastatic breast cancer (MBC) is a biologically distinct subset in which the efficacy of cyclin-dependent kinase 4\/6 (CDK4\/6) inhibitors remains incompletely characterized. We evaluated real-world outcomes and prognostic factors in a multicenter retrospective Turkish cohort treated with a CDK4\/6 inhibitor plus endocrine therapy (June 2020\u2013September 2025). Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan\u2013Meier and Cox methods. Among 121 patients, 30 (24.8%) had BRCA1, 88 (72.7%) had BRCA2, and three (2.5%) had dual mutations; 66.9% received first-line therapy, with ribociclib in 69.4% and palbociclib in 29.8%. Objective response rate was 69.4% and the clinical benefit rate was 82.6%. Median PFS was 17.0 months and OS 47.0 months. PFS was numerically longer in BRCA1 than in BRCA2 carriers (25.0 vs. 14.0 months), although the difference was not statistically significant in the pairwise comparison (HR 1.50, 95% CI 0.88\u20132.56; log-rank p = 0.135); the dual BRCA1\/2 subgroup (n = 3) had the poorest outcomes and was assessed descriptively. OS did not differ significantly between BRCA1 and BRCA2 carriers (57.0 vs. 49.0 months; log-rank p = 0.520). PFS did not differ between ribociclib and palbociclib (p = 0.192); OS favored ribociclib at borderline significance (p = 0.050), but this was not confirmed in Cox regression. In multivariable analysis, ECOG \u2265 1 (HR 1.85; p = 0.010) and fulvestrant-based therapy (HR 1.74; p = 0.041) predicted shorter PFS; fulvestrant also predicted worse OS (HR 2.39; p = 0.008). CDK4\/6 inhibitor-based therapy shows meaningful activity in gBRCAm HR+\/HER2- MBC; the numerically poorer outcomes observed in BRCA2 carriers are hypothesis-generating and warrant validation in larger cohorts.<\/jats:p>","DOI":"10.3390\/curroncol33060365","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T15:11:22Z","timestamp":1781709082000},"page":"365","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Real-World Outcomes of CDK4\/6 Inhibitors in Germline BRCA1\/2-Mutated Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: Turkish Oncology Group (TOG) Study"],"prefix":"10.3390","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4841-7994","authenticated-orcid":false,"given":"Mustafa","family":"Seyyar","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Gaziantep City Hospital, Gaziantep 27470, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0937-0468","authenticated-orcid":false,"given":"Ali","family":"Kalem","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Gaziantep University, Gaziantep 27310, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2079-3350","authenticated-orcid":false,"given":"M\u00fcrsel","family":"Sali","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Bursa Uluda\u011f University, Bursa 16059, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5357-7610","authenticated-orcid":false,"given":"Berkan","family":"Karabu\u011fa","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, Ankara 06200, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3590-0426","authenticated-orcid":false,"given":"Taha Koray","family":"Sahin","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Cancer Institute, Hacettepe University, Ankara 06230, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmet K\u00fcr\u015fad","family":"Di\u015fli","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Erciyes University, Kayseri 38280, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alper","family":"T\u00fcrkel","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Eski\u015fehir City Hospital, Eski\u015fehir 26080, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4821-8143","authenticated-orcid":false,"given":"Berkan","family":"Karadurmu\u015f","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Gulhane Training and Research Hospital, Ankara 06010, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7753-1482","authenticated-orcid":false,"given":"Ece","family":"\u015eahin Haf\u0131zo\u011flu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Celal Bayar University, Manisa 45030, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nil\u00fcfer","family":"Avc\u0131","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, School of Health Sciences Radiotherapy Program, Fenerbah\u00e7e University, Istanbul 34758, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1154-5850","authenticated-orcid":false,"given":"Irem","family":"Bilgetekin","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Ankara Memorial Hospital, Ankara 06520, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3587-2517","authenticated-orcid":false,"given":"Naziyet","family":"K\u00f6se Baytemur","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Ankara Memorial Hospital, Ankara 06520, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1822-3870","authenticated-orcid":false,"given":"Esma","family":"Uguztemur","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Ad\u0131yaman Training and Research Hospital, Adiyaman 02040, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Utku","family":"Oflazo\u011flu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Ataturk Training and Research Hospital, Izmir Katip Celebi University, Izmir 35360, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8639-3076","authenticated-orcid":false,"given":"Hasibe Bilge","family":"G\u00fcr","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sakarya Training and Research Hospital, Sakarya 54100, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0130lhan","family":"Hac\u0131bekiro\u011flu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sakarya Training and Research Hospital, Sakarya 54100, 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T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6zgecan","family":"D\u00fclgar Kaya","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, SBU Umraniye Training and Research Hospital, Istanbul 34764, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melike","family":"Yaz\u0131c\u0131","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Kocaeli University, Kocaeli 41001, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teoman","family":"\u015eakalar","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, HG Hospital, Kahramanmara\u015f 46050, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1235-6739","authenticated-orcid":false,"given":"Seval","family":"Akay","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Izmir City Hospital, Izmir 35540, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2575-5819","authenticated-orcid":false,"given":"Nargiz","family":"Majidova","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, VM Medical Park Maltepe Hospital, Istanbul 34843, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2981-8098","authenticated-orcid":false,"given":"Murad","family":"Guliyev","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Cerrahpa\u015fa Faculty of Medicine, Istanbul University-Cerrahpa\u015fa, Istanbul 34098, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6635-2012","authenticated-orcid":false,"given":"\u00d6zkan","family":"Alan","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Cerrahpa\u015fa Faculty of 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T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bekir","family":"Do\u011fan","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Bak\u0131rk\u00f6y Dr. Sadi Konuk Training and Research Hospital, Istanbul 34147, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet Akif","family":"T\u00fckenmez","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Trabzon University Kanuni Training and Research Hospital, Trabzon 61250, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9110-4280","authenticated-orcid":false,"given":"Teyfik","family":"Demir","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Ondokuz May\u0131s University, Samsun 55139, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1976-3951","authenticated-orcid":false,"given":"Elif","family":"\u015eahin","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Kocaeli City Hospital, Kocaeli 41060, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Engin","family":"Erdemo\u011flu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Medical Park Istanbul Oncology Hospital, Istanbul 34303, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7881-5635","authenticated-orcid":false,"given":"Fatma","family":"Keskin Uzundere","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Dicle University, Diyarbak\u0131r 21280, 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T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9317-942X","authenticated-orcid":false,"given":"Ferhat","family":"Ekinci","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Celal Bayar University, Manisa 45030, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7538-9119","authenticated-orcid":false,"given":"Musa Bar\u0131\u015f","family":"Aykan","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Gulhane Training and Research Hospital, Ankara 06010, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0130smail","family":"Ert\u00fcrk","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Gulhane Training and Research Hospital, Ankara 06010, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6924-9467","authenticated-orcid":false,"given":"Deniz Can","family":"Guven","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Cancer Institute, Hacettepe University, Ankara 06230, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3931-0191","authenticated-orcid":false,"given":"Adem","family":"Delig\u00f6n\u00fcl","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Bursa Uluda\u011f University, Bursa 16059, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cengiz","family":"Kara\u00e7in","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, Ankara 06200, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0182-3933","authenticated-orcid":false,"given":"\u00d6zt\u00fcrk","family":"Ate\u015f","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, Ankara 06200, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mevl\u00fcde","family":"\u0130nan\u00e7","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Erciyes University, Kayseri 38280, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7870-8741","authenticated-orcid":false,"given":"Havva","family":"Ye\u015fil","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Gaziantep University, Gaziantep 27310, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4984-1049","authenticated-orcid":false,"given":"Sercan","family":"Aksoy","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Cancer Institute, Hacettepe University, Ankara 06230, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tolga","family":"K\u00f6\u015feci","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Cukurova University Balcal\u0131 Hospital, Adana 01330, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2360-3392","authenticated-orcid":false,"given":"\u0130lker Nihat","family":"\u00d6kten","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Istanbul Medeniyet University G\u00f6ztepe City Hospital, Istanbul 34722, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3060-377X","authenticated-orcid":false,"given":"Hasan \u00c7a\u011fr\u0131","family":"Y\u0131ld\u0131r\u0131m","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Ege University, Izmir 35100, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7871-6311","authenticated-orcid":false,"given":"Devrim","family":"\u00c7abuk","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Kocaeli University, Kocaeli 41001, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 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