Di Cosimo S, Triulzi T, Pizzamiglio S, et al. - Given that increased pathological complete response (pCR) rate is achieved with dual HER2-inhibition combined with neoadjuvant chemotherapy, researchers examined if the 41-gene classifier TRAR, which was developed to identify trastuzumab responders, could predict pCR to anti-HER2 therapies in the NeoALTTO trial and in turn could assist in selecting patients to minimize overtreatment. In phase 3 NeoALTTO study, TRAR was affirmed to be associated with pCR. Independent of oestrogen receptor and treatment arm, TRAR was predictive of pCR. Compared with both clinicopathological and molecular predictive factors, TRAR performed better. Immune-related features were enriched in tumors with TRAR low scores. These findings support the promising utility of TRAR as a tool to refine the ability to identify patients sensitive to anti-HER2 (including trastuzumab-only)-based therapy and eligible for de-escalated treatment strategies.