Simple SummaryMetaplastic breast carcinoma (MBC) is a rare, heterogenous group of aggressive triple-negative breast cancers with a characteristically poor prognosis and response to standard treatments. The rarity of MBC greatly limits insight into the clinical presentation, management, and scientific investigation. We aimed to evaluate the demographics and characteristics of MBC as well as survival outcomes based on presentation and treatment. Several features regarding tumor size, grade, stage, and patient age were found to be correlated with worse prognosis while the best overall survival was seen in patients who underwent combined surgery, chemotherapy, and radiotherapy. Black patients in the study had significantly worse outcomes than White patients, with higher rates of aggressive tumor features at presentation. The most common genetic mutations observed were TP53, PIK3CA, and LRP1B.AbstractPurpose: In this population-based study, we aim to identify factors that are influential on the survival outcome in MBC and investigate novel molecular approaches in personalized disease management. Methods: The data of this study were collected from the SEER database from 2000–2018. A total of 5315 cases were extracted from the database. The data were evaluated for demographics, tumor characteristics, metastasis, and treatment. Survival analysis was completed by using SAS software for multivariate analysis, univariate analysis, and non-parametric survival analysis. The molecular data with the most common mutations in MBC were extracted from the Catalogue of Somatic Mutations in Cancer (COSMIC) database. Results: The mean age at the time of presentation was 63.1 with a standard deviation (SD) of 14.2 years. Most patients were White (77.3%) with 15.7% Black patients, 6.1% Asian or Pacific Islander, and 0.5% American Indian. Histologically, most of the reported tumors were grade III (74.4%); 37% of the cases were triple negative (ER-, PR- and HER2-), whereas the hormone status was unknown in 46% of the cases. Spread was localized in 67.3% of patients while 26.3% had regional spread and 6.3% had distant metastases. Most tumors were unilateral (99.9%) and between 20–50 mm in size (50.6%). The lungs were the most common site for distant metastasis at diagnosis (3.42%) followed by bone (1.94%), liver (0.98%), and brain (0.56%). A combination of surgery, chemotherapy, and radiation therapy was the most common treatment with a cause-specific survival rate of 78.1% (95% CI = 75.4–80.4). The overall survival rate at 5 years was 63.6% (95% confidence interval (CI) = 62.0–65.1) with a cause-specific survival of 71.1% (95% CI = 69.5–72.6). Cause-specific survival was found to be 63.2% (95% CI = 58.9–67.1) in Black patients as compared to 72.4% (95% CI = 70.1–74.1) in White patients. Black patients also presented with higher rates of grade III disease, distant metastasis, and larger tumor size. On multivariate analysis, age > 60, grade III+, metastasis, and tumor size > 50 mm were associated with worse survival. The most common mutations in MBC identified in COSMIC data were TP53, PIK3CA, LRP1B, PTEN, and KMT2C. Conclusion: Though rare, MBC is aggressive, with poor prognosis associated with high-grade tumors, metastasis, tumor size over 50 mm, and advanced age at the time of presentation. Overall, Black women had worse clinical outcomes. MBC is difficult to treat and carries a poor prognosis that affects various races disproportionately. Continued enhancement of treatment strategies to foster more individualized care as well as continued enrollment in clinical trials are needed to improve outcomes among patients with MBC.