Triulzi, TizianaBianchini, GiampaoloDi Cosimo, SerenaPienkowski, TadeuszIm, Young-HyuckBianchi, Giulia ValeriaGalbardi, BarbaraDugo, MatteoDe Cecco, LorisTseng, Ling-MingLiu, Mei-ChingBermejo, BegoñaSemiglazov, VladimirViale, Giuliade la Haba-Rodriguez, JuanOh, Do-YounPoirier, BrigitteValagussa, PinucciaGianni, LucaTagliabue, Elda2023-05-032023-05-032021-12-17http://hdl.handle.net/10668/22494As most erb-b2 receptor tyrosine kinase 2 (HER2)-positive breast cancer (BC) patients currently receive dual HER2-targeting added to neoadjuvant chemotherapy, improved methods for identifying individual response, and assisting postsurgical salvage therapy, are needed. Herein, we evaluated the 41-gene classifier trastuzumab advantage risk model (TRAR) as a predictive marker for patients enrolled in the NeoSphere trial. TRAR scores were computed from RNA of 350 pre- and 166 post-treatment tumor specimens. Overall, TRAR score was significantly associated with pathological complete response (pCR) rate independently of other predictive clinico-pathological variables. Separate analyses according to estrogen receptor (ER) status showed a significant association between TRAR score and pCR in ER-positive specimens but not in ER-negative counterparts. Among ER-positive BC patients not achieving a pCR, those with TRAR-low scores in surgical specimens showed a trend for lower distant event-free survival. In conclusion, in HER2-positive/ER-positive BC, TRAR is an independent predictor of pCR and represents a promising tool to select patients responsive to anti-HER2-based neoadjuvant therapy and to assist treatment escalation and de-escalation strategies in this setting.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/HER2breast cancergene expression profilepertuzumabpredictive biomarkertrastuzumabAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsFemaleHumansNeoadjuvant TherapyReceptor, ErbB-2TrastuzumabTreatment Outcomeresearch article34816585open access10.1002/1878-0261.131411878-0261PMC9208076https://doi.org/10.1002/1878-0261.13141https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9208076/pdf