The Metaplastic Conundrum: A National Cancer Database Analysis of Metaplastic versus Triple-Negative Ductal Breast Cancer.

Background: Historically, treatment approaches for metaplastic breast cancer (MpBC) have mirrored that of triple-negative ductal breast cancer (TN-IDC), yet MpBC has persistently worse survival. This study describes rates and response to neoadjuvant systemic therapy (NAC) for MpBC and evaluates survival between triple-negative MpBC (TN-MpBC), biomarker-positive MpBC (nTN-MpBC), and TN-IDC by treatment approach.

Methods: The National Cancer Database was queried for females diagnosed with clinically non-metastatic MpBC or TN-IDC from 2011 to 2021. One-to-one propensity score matching between TN-MpBC and TN-IDC patients was performed.

Results: Of 5575 MpBC patients, surgery and chemotherapy rates were high. For patients who received systemic therapy and surgery, an adjuvant approach was favored; however, NAC for TN-MpBC increased from 18.3 to 31.5% by 2021. Higher rates of NAC non-response and lower overall survival were found among MpBC cohorts compared with TN-IDC. For MpBC, an adjuvant approach had significantly better survival than other systemic therapy sequences. When evaluated by pathologic response to NAC, a partial or non-response had worse survival compared with complete response or not undergoing NAC. On Cox proportional hazard regression of matched patients, NAC had an adjusted hazard ratio of 2.56 (1.36-4.79) compared with not undergoing NAC.

Conclusion: MpBC is predominantly treated with surgery and systemic therapy, with increasing rates of NAC for TN-MpBC. However, patients with MpBC have inferior survival to TN-IDC, and NAC for MpBC is associated with worse survival compared with other systemic therapy sequences, unless a complete pathologic response is achieved. These findings reinforce the need for systemic treatment sequence optimization for MpBC.