Rare histologic subtypes of triple-negative breast cancer: The impact of immunotherapy on outcomes for metastatic disease.

1120 Background: The addition of immunotherapy (IO) to chemotherapy (chemo) has significantly improved survival for patients with PD-L1-positive, metastatic triple-negative breast cancer (mTNBC), establishing chemo+IO as the standard first-line treatment in this population. However, the impact of IO on real-world outcomes of rare histologic subtypes of TNBC, such as metaplastic and lobular, as well as inflammatory presentation, are unknown. Methods: We conducted a retrospective study analyzing data from the US National Cancer Database (NCDB). Patients diagnosed with de novo stage IV TNBC who received chemo alone or chemo+IO between 2019 and 2022 (after FDA approval of IO for mTNBC) were included. mTNBC was classified as ductal, lobular, inflammatory, metaplastic, or other by the NCDB. Overall survival (OS) was assessed using the Kaplan-Meier method and multivariable Cox regression models controlled for sociodemographic and clinicopathologic factors. Results: A total of 6,711 patients with de novo mTNBC were identified (mean age 59.2 years), with a median follow-up of 19.8 months. Ductal histology was the most common (74.2%), followed by inflammatory (8.7%), metaplastic (4.5%), and lobular (3.6%) cases. Overall, 40.0% of the patients received chemo+IO. Immunotherapy use was the highest in mTNBC with inflammatory presentation (46.8%), followed by ductal (40.0%), lobular (37.5%), and metaplastic (37.2%) subtypes ( P = 0.002). Among patients who received chemo+IO, the median OS time was the longest in ductal mTNBC (30.3 months) compared to the lobular (23.5 months) and metaplastic (22.9 months) subtypes and inflammatory presentation (16.5 months) (log-rank test P < 0.001). In the adjusted models, inflammatory mTNBC had a significantly higher risk of mortality than ductal cases treated with chemo+IO (adjusted hazard ratio [aHR], 1.96; 95% CI, 1.31–2.92); lobular (aHR, 1.59; 95% CI, 0.84–3.00) and metaplastic (aHR, 1.10; 95% CI, 0.44–2.71) subtypes also had a higher mortality risk, though the differences were not statistically significant due to small group sample sizes. Among patients who received chemo alone, inflammatory presentation (aHR, 2.10; 95% CI, 1.58–2.80) and lobular subtype (aHR, 1.67; 95% CI, 1.03–2.70) also had a higher risk of mortality than the ductal subtype. Conclusions: In this real-world analysis, patients with inflammatory, lobular, and metaplastic de novo mTNBC continued to experience inferior survival outcomes despite the use of chemo+IO. Our findings highlight persistent disparities in mortality outcomes and support the need for biomarker-driven strategies and dedicated clinical trials for these rare subtypes and inflammatory mTNBC.