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

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.

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Journal
Current Oncology
Published
2026-06-17
DOI
https://doi.org/10.3390/curroncol33060365
Primary Topic
Advanced Breast Cancer Therapies
Type
article
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article

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

Naziyet Köse Baytemür, Özkan Alan, Osman Köstek, Fatma Keskin Uzundere et al.
Current Oncology
Advanced Breast Cancer Therapies
article

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

Naziyet Köse Baytemür, Özkan Alan, Osman Köstek, Fatma Keskin Uzundere, Nargız Majidova, Osman Butun, Mehmet Uzun, Adem Deligönül, Hasibe Bilge Gür, Gökşen İnanç İmamoğlu, Mehmet Akif Tükenmez, İlhan Hacıbekiroğlu, Taha Koray Şahin, Elanur Karaman, Ali Kaan Güren, Berkan Karadurmuş, İsmail Ertürk, Murad Guliyev, Shamkhal Safarov, Berkan Karabuğa, Hacı Arak, Mürsel Salı, Havva Yeşil Çınkır, Esma Uguztemur, Teoman Şakalar, Sercan Aksoy, Musa Barış Aykan, Ayberk Bayramgil, Sernaz Uzunoğlu, İlker Ökten, Tuba Baydas, İrem Bilgetekin, Hasan Çağrı Yıldırım, Teyfik Demir, Mustafa Seyyar, Öztürk Ateş, Bülent Karabulut, Utku Oflazoğlu, Engin Erdemoğlu, Alper Türkel, Esra Aydın, Seval Akay, Ferhat Ekinci, Devrim Çabuk, Tolga Köşeci, Elif Şahin, Ali̇ Kalem, Serkan Gülcü, Deniz Can Güven, Banu Öztürk, Tulay Eren, Ece Şahin Hafızoğlu, Nilüfer Avcı, Ahmet Unlu, Bekir Dogan, Aysun Fatma Akkuş, Özgecan Dülgar Kaya, Ahmet Kürşad Dişli, Melike Yazıcı, Mevlüde İnanç, Cengiz Karaçin
article en

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.

Current OncologyVol. 33(6)
Dicle University (TR), Trakya University (TR), Bursa Uludağ Üni̇versi̇tesi̇ (TR), Izmir University (TR), Recep Tayyip Erdoğan University (TR), Karadeniz Technical University (TR), Manisa Celal Bayar University (TR), Adıyaman University (TR), Ondokuz Mayıs University (TR), Izmir Kâtip Çelebi University (TR), Kent Hospital (US), Fenerbahçe University (TR), Ege University (TR), Gülhane Askerî Tıp Akademisi (TR), Eskişehir City Hospital (TR), Memorial Ankara Hospital (TR), Uni Research (Norway) (NO), Istanbul Metropolitan Municipality (TR), Ankara Onkoloji Eğitim ve Araştırma Hastanesi (TR), Antalya Eğitim ve Araştırma Hastanesi (TR), Ümraniye Eğitim ve Araştırma Hastanesi (TR), Istanbul University-Cerrahpaşa (TR), Medical Park Gaziantep Hospital (TR), Hacettepe University Hospital (TR), Sakarya Eğitim ve Araştırma Hastanesi (TR), Bakırköy Dr.Sadi Konuk Eğitim ve Araştırma Hastanesi (TR), Izmir Tepecik Eğitim ve Araştırma Hastanesi (TR), Istanbul Eye Hospital (TR), Kent Hastanesi (TR), Maltepe University (TR), Kahramanmaraş Sütçü İmam University (TR), Kocaeli Üniversitesi (TR), Cukurova University (TR), Istanbul Medeniyet University (TR), Gaziantep University (TR), Hacettepe University (TR), Marmara University (TR), Erciyes University (TR)
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