Purpose <p>Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with a high risk of early central nervous system dissemination and poor outcomes after brain metastasis (BM). This systematic review summarizes current evidence on incidence, treatment strategies, outcomes, guidelines, and ongoing trials in TNBC-associated BM.</p> Methods <p>The review followed PRISMA guidance and was registered in the Open Science Framework (OSF.IO/6TDRF). MEDLINE, Scopus, Web of Science, DOAJ, and ClinicalTrials.gov were searched through January 17, 2026. Eligible records comprised randomized trials, prospective, retrospective, and ambispective cohorts, registry analyses, case series, guideline or consensus documents, and registered clinical trials reporting TNBC-specific CNS data. Data were extracted independently and synthesized descriptively because clinical and methodological heterogeneity precluded quantitative meta-analysis.</p> Results <p>Forty-three records met the inclusion criteria: 27 clinical studies (25 addressing parenchymal brain metastases and two addressing leptomeningeal metastases), seven guideline or consensus documents, and nine ongoing clinical trials. Across clinical studies, 67,290 patients were included; 2,555 patients had TNBC and developed CNS involvement. SRS achieved 1-year local control rates of 90–99% in selected patients with limited intracranial disease, but distant intracranial relapse remained frequent. Whole-brain radiotherapy was commonly used for extensive disease and was associated with poorer survival in observational cohorts. Among systemic options, sacituzumab govitecan had the most consistently reported TNBC-specific intracranial signal, although current evidence did not establish comparative superiority.</p> Conclusion <p>TNBC-associated BM remains linked to substantial morbidity, mortality, and limited prospective evidence. SRS is preferred for appropriately selected patients with limited disease. Sacituzumab govitecan has the most consistently reported TNBC-specific CNS activity, but no systemic agent has established superiority in prospective TNBC-specific CNS trials.</p> Clinical trial number <p>Not applicable.</p>

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Brain metastases in triple-negative breast cancer: a systematic review of current trends, treatment strategies, and outcomes

  • Emir Begagić,
  • Hakija Bečulić,
  • Amila Kovčić Harčinović,
  • Nejla Huseinspahić,
  • Emir Bećirović,
  • Omar Tluli,
  • Krešimir Tomić,
  • Semir Vranić

摘要

Purpose

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with a high risk of early central nervous system dissemination and poor outcomes after brain metastasis (BM). This systematic review summarizes current evidence on incidence, treatment strategies, outcomes, guidelines, and ongoing trials in TNBC-associated BM.

Methods

The review followed PRISMA guidance and was registered in the Open Science Framework (OSF.IO/6TDRF). MEDLINE, Scopus, Web of Science, DOAJ, and ClinicalTrials.gov were searched through January 17, 2026. Eligible records comprised randomized trials, prospective, retrospective, and ambispective cohorts, registry analyses, case series, guideline or consensus documents, and registered clinical trials reporting TNBC-specific CNS data. Data were extracted independently and synthesized descriptively because clinical and methodological heterogeneity precluded quantitative meta-analysis.

Results

Forty-three records met the inclusion criteria: 27 clinical studies (25 addressing parenchymal brain metastases and two addressing leptomeningeal metastases), seven guideline or consensus documents, and nine ongoing clinical trials. Across clinical studies, 67,290 patients were included; 2,555 patients had TNBC and developed CNS involvement. SRS achieved 1-year local control rates of 90–99% in selected patients with limited intracranial disease, but distant intracranial relapse remained frequent. Whole-brain radiotherapy was commonly used for extensive disease and was associated with poorer survival in observational cohorts. Among systemic options, sacituzumab govitecan had the most consistently reported TNBC-specific intracranial signal, although current evidence did not establish comparative superiority.

Conclusion

TNBC-associated BM remains linked to substantial morbidity, mortality, and limited prospective evidence. SRS is preferred for appropriately selected patients with limited disease. Sacituzumab govitecan has the most consistently reported TNBC-specific CNS activity, but no systemic agent has established superiority in prospective TNBC-specific CNS trials.

Clinical trial number

Not applicable.