Abstract
Purpose
Optimizing metaplastic breast cancer (MpBC) management remains an unmet clinical need. Current literature on MpBC response toantibody drug-conjugates is limited to individual case reports and case series. This study investigates outcomes in metastatic MpBC treated withsacituzumab govitecan (SG) and characterizes actionable targets to inform future studies.Methods
Patients (pts) with metastatic triple negative breastcancer (TNBC) treated at the Massachusetts General Hospital Cancer Center between 2000 and 2025 were assessed for MpBC and receipt of SG. MpBCcases were interrogated for biomarkers qualifying for targeted therapy: HER2-low status (IHC 1+/2+), combined positive score (CPS), and targetablegenomic variants based on next-generation sequencing of plasma and/or tissue ordered by the treating provider. Multivariable Cox regression analysisassessed the association of MpBC under SG treatment with progression-free survival (PFS) and overall survival.Results
MpBC cases (n = 17) had anumerically shorter median PFS under SG compared to non-MpBC TNBC (n = 133) [2.6 vs. 6.8 months, p = 0.16]. While most patients with MpBC hadlimited response to SG monotherapy, two patients on SG + talazoparib had prolonged PFS. Annotation of available genomic and pathology data from allpatients with MpBC (n = 58) revealed targetable alterations including 34/56 patients with HER2-low status, 8/45 patients with germline BRCA1/2mut, and9/30 patients with somatic PIK3CAmut. MpBC response to matched therapies showed variable PFS.Conclusion
To our knowledge, this study is one ofthe largest analyses of MpBC response to SG and highlights challenges of treating rare diseases at large. Multi-institutional collaboration and inclusive trialdesign are essential to optimize treatments for MpBC.