Matthew Kurian, Physician at St. Elizabeth Healthcare, shared on LinkedIn:

“TALENT at ESMO – European Society for Medical Oncology 2026: T-DXd in Early HER2-Low Breast Cancer.

The phase II TALENT trial evaluated neoadjuvant T-DXd in HR+/HER2-low early breast cancer, with modest pCR rates:

T-DXd alone: 7% pCR,
T-DXd + anastrozole: 3% pCR,
T-DXd to chemotherapy: 9% pCR.

Adding endocrine therapy offered no benefit, while sequential chemotherapy modestly increased pCR with greater toxicity.

The more interesting findings were translational:

Higher baseline quantitative HER2 expression correlated with pCR (P = .0329).
HER2 expression declined after T-DXd, while TROP2 remained stable.

My takeaway

ADC activity is evident, but replacing chemotherapy in early HR+ disease remains challenging. The future may lie in quantitative biomarker selection and rational combinations rather than ADC monotherapy.

Importantly, pCR is an imperfect surrogate in HR+ disease. We can’t expect pCR rates like in HER2 and triple negative disease given so much heterogeneity of disease- some more basal like and luminal B vs luminal A will play a major factor into this. Longer-term outcomes will matter.”