Oncology · Medical Literature
Brain metastases in triple-negative breast cancer: a systematic review of current trends, treatment strategies, and outcomes.
Abstract
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. 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. 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. 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. Not applicable.
Clinical relevance
What is the current evidence on the incidence, treatment strategies, clinical outcomes, practice guidelines, and ongoing trials relevant to brain metastases arising in patients with triple-negative breast cancer? __SNAPSHOT__ {"studyDesign":"Systematic review (descriptive synthesis; quantitative meta-analysis not performed due to clinical and methodological heterogeneity); conducted in accordance with PRISMA guidance and prospectively registered in the Open Science Framework (OSF.IO/6TDRF)","setting":"Multinational; searches encompassed MEDLINE, Scopus, Web of Science, DOAJ, and ClinicalTrials.gov; literature search date through January 17, 2026","sampleSize":"43 records included: 27 clinical studies (25 addressing parenchymal brain metastases, 2 addressing leptomeningeal metastases), 7 guideline or consensus documents, and 9 ongoing clinical trials; 67,290 patients represented across clinical studies (abstract truncated — full denominator not confirmed)","population":"Patients with triple-negative breast cancer (TNBC) and central nervous system involvement, specifically parenchymal brain metastases or leptomeningeal metastases; study designs included randomized trials, prospective cohorts, retrospective and ambispective cohorts, registry analyses, and case series reporting TNBC-specific CNS data","intervention":"All treatment strategies for TNBC-associated brain metastases reported in included studies (local therapies, systemic therapies, and combinations thereof); specific interventions not enumerated in the available abstract","comparator":"Variable by included study; no single universal comparator — descriptive synthesis across heterogeneous study designs","primaryOutcome":"Not defined as a single primary endpoint (consistent with systematic review methodology); outcomes of interest included incidence of brain metastases, treatment strategies employed, and clinical outcomes; specific outcome metrics (e.g., overall survival, intracranial progression-free survival) not delineated in the available abstract","followUp":"Not reported (varies by individual included study)","fundingSource":"Not reported in the available abstract"}
Key findings
The full results section is not available; the abstract was truncated after reporting that 43 records met inclusion criteria and that 67,290 patients were represented across 27 clinical studies (the abstract text ends mid-sentence). Therefore, specific effect sizes, survival data, response rates, p-values, confidence intervals, and NNT/NNH cannot be reported — none were available in the provided abstract. Structurally, the review identified a marked predominance of retrospective evidence: 25 of 27 clinical studies addressed parenchymal brain metastases, while only 2 addressed leptomeningeal metastases, underscoring a critical evidence gap for the latter. The identification of 9 ongoing clinical trials signals an actively evolving landscape. No pooled quantitative estimates were generated, as the authors explicitly precluded meta-analysis on the basis of clinical and methodological heterogeneity. No adverse event data were extractable from the available abstract.
Practice implications
This systematic review maps the current evidence landscape for TNBC-associated brain metastases but does not, in its available form, generate practice-changing quantitative estimates. TNBC is established as the breast cancer subtype with the highest propensity for CNS dissemination, and brain metastases in this context carry a prognosis that is generally worse than that observed in hormone receptor-positive or HER2-positive subtypes — a point corroborated by the broader literature. The descriptive synthesis design is methodologically appropriate given the marked heterogeneity across included studies, but it means that the review cannot establish superiority of one treatment approach over another. Patients with leptomeningeal disease are profoundly underrepresented (n=2 studies), and findings from the parenchymal brain metastasis literature should not be extrapolated to this subgroup. The large cumulative sample size (67,290) reflects the aggregation of heterogeneous historical cohorts and does not confer the evidentiary weight of a pooled prospective analysis. The 9 registered ongoing trials identified suggest that the field anticipates near-term prospective data; current practice should be guided by existing multidisciplinary guidelines, tumor board consensus, and enrollment in clinical trials where feasible. IMPORTANT NOTE: This summary is based solely on the truncated abstract as provided; the full manuscript was not available for review, and additional findings, subgroup analyses, and nuanced conclusions present in the full text cannot be captured here. __LIMITATIONS__ Abstract truncated — the full results, discussion, and conclusions of the manuscript were not available; this summary reflects only what was reported in the supplied abstract excerpt.,Descriptive synthesis only; clinical and methodological heterogeneity explicitly precluded quantitative meta-analysis, limiting the ability to derive pooled effect estimates or rank treatment strategies.,Predominance of retrospective and observational study designs among the 27 clinical studies, with inherent risks of selection bias, confounding, and variable reporting standards across institutions and time periods.,Marked underrepresentation of leptomeningeal metastases (only 2 of 27 clinical studies), a clinically relevant and often fatal complication of TNBC.,Literature search cutoff of January 17, 2026, means recently published trial data or guideline updates may not be captured.,Patient-level data were not available; aggregate synthesis cannot account for confounders such as performance status, extent of extracranial disease, prior treatment exposure, or BRCA mutation status.,Inclusion of case series and registry analyses alongside randomized trials introduces substantial variation in evidence quality without formal GRADE or risk-of-bias stratification described in the available abstract.,Generalizability may be limited if included studies over-represent high-resource academic centers or specific geographic/ethnic populations.,Funding source not reported; potential for publication bias in the included literature cannot be assessed.,The large cumulative patient count (67,290) should not be interpreted as a single unified cohort; it reflects the sum of heterogeneous historical datasets. __BOTTOM_LINE_CATEGORY__ low_certainty __BOTTOM_LINE__ This PRISMA-registered systematic review synthesizes evidence on brain metastases in TNBC across 43 records representing over 67,000 patients but is limited to a descriptive analysis due to prohibitive heterogeneity, and the available abstract is truncated, precluding extraction of specific outcomes data. The review confirms a critical evidence gap — particularly for leptomeningeal disease — and identifies 9 ongoing trials that may generate the prospective, TNBC-specific CNS data currently lacking. Clinicians should continue to manage TNBC-associated brain metastases through multidisciplinary tumor boards, adhere to current guideline recommendations, and prioritize clinical trial enrollment.