Abstract Background: Prior studies of metastatic triple-negative breast cancer (TNBC) have generally categorized multiple metastatic sites broadly as “multiple” or have focused on single-organ involvement, limiting the ability to counsel patients on prognosis for specific metastatic groups. To assist oncologists in these discussions, we analyzed how site-specific patterns of distant metastasis affected survival and treatments received for de-novo stage IV TNBC using a large, real-world national registry. Methods: Using the National Cancer Database (NCDB), we identified women over age 40 who were diagnosed with de-novo stage IV TNBC between 2010 and 2020. Metastatic groups were classified as brain only, lung only, liver only, or combinations of these sites at diagnosis. We focused only on brain, lung, and liver involvement because bone metastases are known to have a more favorable prognosis. Median overall survival (OS) and six-month and one-year survival rates were calculated using Kaplan-Meier analysis. Multivariate Cox regression analyzed associations between metastatic group and two-year OS after adjustment for age, comorbidity index, race/ethnicity, facility type, and diagnosis year. Treatment patterns were summarized for each metastatic group. Results: We identified 119,373 women with stage IV breast cancer, of whom 13,345 (11.2%) had TNBC. After excluding patients with missing variable data, 7,448 women comprised the final cohort for analysis. Median OS by metastatic group ranged from 3.6 months (brain + liver) to 12.7 months (lung only). In ascending order, one-year OS rates were 13.1% for brain + lung + liver, 17.3% for brain + liver, 29.2% for brain + lung, 30.8% for brain only, 34.0% for lung + liver, 47.6% for liver only, and 51.8% for lung only. In multivariate Cox regression, compared to brain only, patients with metastases to lung only (adjusted hazard ratio aHR 0.55, 95% confidence interval CI 0.49-0.61, p0.001) and liver only (aHR 0.69, 95% CI 0.62-0.77, p0.001) had increased two-year OS, while patients with metastases to brain + liver (aHR 1.67, 95% CI 1.37-2.03, p0.001) and brain + lung + liver (aHR 1.72, 95% CI 1.47-2.01, p0.001) had worse OS. Chemotherapy receipt ranged from 57.0% (brain + liver) to 75.7% (liver only). Radiation was most common in patients with CNS involvement, ranging from 60.6% (brain + liver) to 69.9% (brain + lung). Surgery to the primary breast site was rare, highest in lung only (27.1%) and lowest in brain + liver (6.3%). Conclusions: Sites of distant metastasis at diagnosis strongly influenced survival and treatment choice in stage IV TNBC. Patients with lung-only metastases showed the highest OS, while those with brain and/or liver involvement had markedly worse OS. These results can help guide clinicians and patients in counseling, expectations, and treatment planning for stage IV TNBC. Citation Format: S. M. Doss, P. Raval. Specific site of metastasis in stage IV triple-negative breast cancer: a national registry analysis of survival outcomes and treatment patterns abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-03-02.
Doss et al. (Tue,) studied this question.