A population-based analysis of treatment and outcomes in 2,500 metaplastic breast cancer patients

532 Background: Metaplastic breast cancer (MBC) is a rare, aggressive variant that is often triple negative (TN). Current guidelines recommend use of standard receptor-based treatment for MBC despite evidence of chemoresistance. We sought to compare treatment patterns and outcomes of MBC and non-MBC. Methods: Women age > 18 with stage I-III MBC and non-MBC histology diagnosed from 2010-2013 were identified in the National Cancer Database. Kaplan Meier and multivariate Cox proportional hazards models were used to estimate MBC association with overall survival (OS). Subgroup analyses were conducted for (1) MBC patients only and (2) TN MBC and TN non-MBC patients. Results: 2451 MBC and 568,057 non-MBC patients were included. 70.3% of MBC were TN vs 11.3% of non-MBC (p < 0.001). 19.2% of MBC were luminal (i.e., ER+ and/or PR+, and HER2-). MBC presented with higher clinical T stage (cT4: 5.4% vs 1.8%) and grade (grade 3: 72.1% vs 29.7%) but was less frequently node-positive (19.1% vs 29.7%, all p < 0.001). A higher proportion of MBC patients were treated with mastectomy (59.0% vs 44.9%), axillary dissection (ALND, 35.2% vs 32.2%), and chemotherapy (74.1% vs 43.1%, all p≤0.001). 5-year OS was reduced among MBC vs non-MBC patients for both the entire cohort (72.7% vs 87.5%) and the TN-only analysis (71.1% vs 77.8%, both log-rank p < 0.001). Among MBC cases, TN subtype was not associated with worse OS than the luminal subtype (HR 1.16, p = 0.28). Chemotherapy (HR 0.69, p = 0.004) and/or radiotherapy (HR 0.52, p < 0.001) improved OS in MBC, and the proportional benefit of chemotherapy did not vary with pathological T or N stage (interaction p > 0.05 for both). Among TN patients, a higher proportion of TN MBC patients underwent mastectomy (58.4% vs 49.5%, p < 0.001), but in contrast to the full cohort, a lower proportion of TN MBC patients received chemotherapy (76.6% vs. 78.7%, p = 0.008) and ALND (35.2% vs. 38.2%, p = 0.01) vs TN non-MBC patients. Conclusions: MBC had worse OS vs non-MBC, and unlike other histologies, outcome was not driven by receptor status. Multimodal therapy improved outcomes. Further investigation into MBC tumor biology and the development of MBC-specific guidelines could potentially improve treatment standardization and outcomes.