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
Year: 2026
Type: article
Study design: Observational Study
Abstract: 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–September 2025). Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan–Meier 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 0.88–2.56; 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 ≥ 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.
Source: Current Oncology
Authors: Mustafa Seyyar, Ali Kalem, Mürsel Sali, Berkan Karabuğa, Taha Koray Sahin, Ahmet Kürşad Dişli, Alper Türkel, Berkan Karadurmuş, Ece Şahin Hafızoğlu, Nilüfer Avcı, Irem Bilgetekin, Naziyet Köse Baytemur, Esma Uguztemur, Utku Oflazoğlu, Hasibe Bilge Gür, İlhan Hacıbekiroğlu, Aysun Fatma Akkuş, Sernaz Topaloğlu, Ayberk Bayramgil, Özgecan Dülgar Kaya, Melike Yazıcı, Teoman Şakalar, Seval Akay, Nargiz Majidova, Murad Guliyev, Özkan Alan, Serkan Gülcü, Tülay Eren, Gökşen İnanç İmamoğlu, Ali Kaan Güren, Osman Köstek, Ahmet Ünlü, Banu Ozturk, Esra Aydın, Shamkhal Safarov, Bekir Doğan, Mehmet Akif Tükenmez, Teyfik Demir, Elif Şahin, Engin Erdemoğlu, Fatma Keskin Uzundere, Osman Bütün, Bülent Karabulut, Mehmet Uzun, Tuba Baydaş, Elanur Karaman, Hacı Arak, Ferhat Ekinci, Musa Barış Aykan, İsmail Ertürk, Deniz Can Guven, Adem Deligönül, Cengiz Karaçin, Öztürk Ateş, Mevlüde İnanç, Havva Yeşil, Sercan Aksoy, Tolga Köşeci, İlker Nihat Ökten, Hasan Çağrı Yıldırım, Devrim Çabuk
Institutions: Gaziantep Şehir Hastanesi, Gaziantep University, Bursa Uludağ Üni̇versi̇tesi̇, Ankara Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, Hacettepe University, Erciyes University, Eskişehir City Hospital, Gülhane Eğitim ve Araştırma Hastanesi, Manisa Celal Bayar University, Fenerbahçe University, Memorial Ankara Hospital, Adıyaman Eğitim ve Araştırma Hastanesi, Izmir Kâtip Çelebi University, Sakarya Eğitim ve Araştırma Hastanesi, Trakya University, Ümraniye Eğitim ve Araştırma Hastanesi, Sağlık Bilimleri Üniversitesi, Kocaeli Üniversitesi, İzmir Şehir Hastanesi, Istanbul University-Cerrahpaşa, Istanbul University, Ankara Etlik City Hospital, Marmara Üniversitesi Eğitim ve Araştırma Hastanesi, Marmara University, Antalya Eğitim ve Araştırma Hastanesi, Recep Tayyip Erdoğan University, İstanbul Başakşehir Çam ve Sakura Şehir Hastanesi, Bakırköy Dr.Sadi Konuk Eğitim ve Araştırma Hastanesi, Trabzon University, Ondokuz Mayıs University, Dicle University, Kent Hastanesi, Izmir Tepecik Eğitim ve Araştırma Hastanesi, Medeniyet Üniversitesi Göztepe Eğitim ve Araştırma Hastanesi, Istanbul Medeniyet University, Karadeniz Technical University, Cukurova University, Ege University
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,654
OpenAlex ID: W7165021748