Expression of HER2, HER3, and TROP2 in primary tumors and brain metastases of breast cancer

Background Human epidermal growth factor receptor 2 (HER2)-directed antibody–drug conjugate (ADC) therapy has shown efficacy in HER2-positive breast cancer brain metastases. However, there is still an unmet medical need for further exploration of other suitable targets for ADCs in brain metastases (BMs). Methods The expression of HER2, HER3, and trophoblast surface antigen 2 (TROP2) was evaluated using immunohistochemistry (IHC) in pairs of primary tumors (PTs) and surgically resected BMs from 44 patients with breast cancer. Expression levels were classified as 0, 1+, 2+, or 3 + based on IHC intensity and the proportion of positive cells. Results The analysis revealed that HER3 and TROP2 expression (IHC ≥ 1+) was observed in all but one BM specimen. TROP2 was highly expressed (IHC ≥ 2+) in both BMs and PTs (86% and 70%, respectively; p = 0.11). High expression of HER3 was more frequent in BMs than in PTs (91% and PTs 59%, respectively; p < 0.01), regardless of breast cancer subtype. In individual paired samples, 95.5% (42/44) exhibited equal or higher HER3 expression in BMs than in PTs. In contrast, high HER2 expression (IHC ≥ 2+) was observed in similar proportions between BMs and PTs (43% and 41%, respectively; p = 1.00). Conclusions The observation of more frequent high-level expression of HER3 in BMs than in PTs, and high-level expression of TROP2 in both BMs and PTs suggests the potential of HER3- and TROP2-based ADC therapy for BMs from breast cancer. Further prospective studies are warranted to validate this hypothesis.