22C3; CPS >1%, SP142: IC >1%).High tumor mutational burden (TMB-H) was defined as >10 mut/MB.Cell infiltration in the tumor microenvironment was estimated by quanTIseq.Real world overall survival (OS) was inferred from insurance claims data and calculated from time of biopsy to last contact.Results: mTNBC more frequently harbored alterations in PIK3CA (45% vs 15%), pTERT (40% vs 3%) and PTEN (17% vs 8%), with higher prevalence of PD-L1 expression (22C3: 46% vs 35%; SP142: 59% vs 44%) (p<0.05).ERBB3-High mTNBC was more frequently associated with mutations in TP53 (86% vs 58%), RB1 (15% vs 2%), KMT2C (10% vs 1%) and TMB-H (12% vs 1%), while ERBB3-Low associated with mutations in PIK3CA (56% vs 33%) and pTERT (59% vs 17%) (p<0.05).Proinflammatory immune cell fractions were higher in ERBB3-High samples, while anti-inflammatory cell fractions were higher in ERBB3-Low.Interestingly, patients with ERBB3-High mTNBC had prolonged OS compared to those with ERBB3-Low (HR = 0.57, 95% CI (0.39 -0.83); median 31 vs. 20 months; p=0.0032). Conclusions:We observed an improvement in OS in patients with ERBB3-High mTNBC, suggesting that ERBB3 may represent a prognostic biomarker in this rare subtype.This work also highlights a potential treatment strategy for this chemo-refractory rare cancer and supports further investigation of HER3-targeting antibodies (such as Patritumab-deruxtecan) with or without checkpoint blockade for mTNBC.Validation in a larger cohort with corresponding clinicopathological data is in progress.
Peuter et al. (2026) studied this question.