Open Access

ARTICLE

Impact of Germline BRCA1/2 Mutations on Clinical Outcomes in Metastatic Triple-Negative Breast Cancer Patients Treated with Sacituzumab Govitecan—An International CEBCC Study from Poland, the Czech Republic and Slovakia

Renata Pacholczak-Madej^1,2,*, Mirosława Püsküllüoğlu^3,*, Anna Polakiewicz-Gilowska⁴, Małgorzata Pieniążek⁵, Iveta Kolářová⁶, Miroslava Malejčíková⁷, Lenka Rušinová⁸, Miloš Holánek⁹, Renata Soumarová¹⁰, Karolina Winsko-Szczęsnowicz¹¹, Justyna Żubrowska¹², Aleksandra Konieczna¹³, Agnieszka Młodzińska¹³, Daniel Krejčí¹⁴, Iwona Danielewicz¹⁵, Magdalena Szymanik-Resko¹⁵, Tomasz Ciszewski¹⁶, Maja Lisik-Habib¹⁷, Anika Pękala¹⁷, Hana Študentová¹⁸, Jan Šustr¹⁹, Bogumiła Czartoryska-Arłukowicz¹¹, Aleksandra Łacko⁵, Jolanta Smok-Kalwat¹², Michał Jarząb⁴, Zuzana Bielčiková²⁰, Marcin Kubeczko⁴
1 Department of Gynecological Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Kraków Branch, Kraków, Poland
2 Department of Anatomy, Jagiellonian University Medical College, Krakow, Poland
3 Department of Clinical Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Kraków Branch, Kraków, Poland
4 Breast Cancer Center, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice, Poland
5 Lower Silesian Comprehensive Cancer Center, Wrocław Medical University, Wrocław, Poland
6 Department of Oncology and Radiotherapy, Faculty of Medicine in Hradec Králové and University Hospital in Hradec Králové, Charles University, Hradec Králové, Czech Republic
7 Oncology Clinic of LFUK, National Cancer Institute, Bratislava, Slovakia
8 Department of Oncology, Stefan Kukura Hospital Michalovce, Michalovce, Slovakia
9 Department of Comprehensive Cancer Care, Faculty of Medicine, Masaryk University, and Masaryk Memorial Cancer Institute, Brno, Czech Republic
10 Department of Oncology, Third Faculty of Medicine, Charles University, University Hospital Kralovské Vinohrady, Prague, Czech Republic
11 Department of Clinical Oncology, Maria Sklodowska-Curie Bialystok Oncology Center, Białystok, Poland
12 Department of Clinical Oncology, Holy Cross Cancer Center, Kielce, Poland
13 Department of Breast Cancer and Reconstructive Surgery, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
14 Department of Oncology, First Faculty of Medicine, Charles University in Prague, and Bulovka University Hospital, Prague, Czech Republic
15 Department of Oncology and Radiotherapy, Szpitale Pomorskie sp. z o.o., Gdynia, Poland
16 Department of Metabolic Diseases and Immuno-Oncology, Medical University of Lublin, Lublin, Poland
17 Department of Proliferative Diseases, Nicolaus Copernicus Multidisciplinary Centre for Oncology and Traumatology, Lodz, Poland
18 Department of Oncology, Faculty of Medicine and Dentistry, Palacky University and University Hospital, Olomouc, Czech Republic
19 Department of Oncology and Radiotherapy, Faculty of Medicine in Pilsen, Charles University, and University Hospital Pilsen, Plzen, Czech Republic
20 Department of Oncology, First Faculty of Medicine, Charles University, and General University Hospital, Prague, Czech Republic
* Corresponding Author: Renata Pacholczak-Madej. Email: ; Mirosława Püsküllüoğlu. Email:

Oncology Research https://doi.org/10.32604/or.2026.076384

Received 19 November 2025; Accepted 10 March 2026; Published online 20 April 2026

Abstract

Background: Germline breast cancer susceptibility gene 1/2 (BRCA1/2) variants guide breast cancer treatment, but their clinical relevance in metastatic triple-negative breast cancer (mTNBC) treated with sacituzumab govitecan (SG) remains unclear. The study aimed to evaluate the association between BRCA status and outcomes in SG-treated mTNBC. Methods: We retrospectively analyzed 264 patients with mTNBC and known germline BRCA1/2 (gBRCA1/2) status who received SG between August 2021 and May 2025 across multiple oncology centers in Poland, the Czech Republic and Slovakia. Survival outcomes were compared between patients with gBRCA1/2 mutations (gBRCA1/2m) and those with gBRCA1/2 wild-type (gBRCA1/2wt) using Kaplan–Meier estimates, the log-rank test, and multivariable Cox proportional hazards models. Two-sided p < 0.05 was considered statistically significant. Results: Among 264 patients, 35 (13.3%) were gBRCA1/2m and 229 (86.7%) were gBRCA1/2wt. After a median follow-up of 9.9 months, the median progression-free survival (PFS) was 4.5 months (95% confidence interval [CI] 2.1–6.3) in gBRCA1/2 carriers versus 4.2 months (95% CI 3.5–5.8) in gBRCA1/2wt patients (p = 0.10). Median overall survival (OS) was 9.1 months (95% CI 5.0–15.1) in gBRCA1/2 carriers compared to 11.5 months (95% CI 10.3–13.5) in gBRCA1/2wt patients (p = 0.26). Brain metastases were more frequent in carriers (20% vs. 8.3%, p = 0.06). In multivariable analysis, Eastern Cooperative Oncology Group (ECOG) performance status was the only independent predictor of poorer survival (hazard ratio 1.97, 95% CI 1.42–2.74, p < 0.01), while gBRCA1/2 status showed no independent association. Conclusions: In this large retrospective cohort of mTNBC patients treated with SG, the presence of gBRCA1/2 was not associated with statistically significant differences in PFS or OS.

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Keywords

Triple-negative breast cancer; sacituzumab govitecan; BRCA1/2 germline mutations; real-world evidence; international multicenter cohort

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