Shai, AyeletWildiers, HansVenieri, ClaudioPogoda, KatarzynaLinderholm, BarbroLambertini, MatteoMatos, LeonorD'Esposito, Eleonora De MaioHajjaji, NawaleMatos, ErikaCortijo, Lucía GonzálezFotia, GiuseppeFortuna, AnaSella, TalGouveia, HelenaRosset, LaurentConstantinidou, AnastasiaAngeli, EurydiceCicin, IrfanTjan-Heijnen, VivianneRuyssers, NatachaDemasure, SofieRemilah, Areen AbuHuygh, GreetShimon, Shani PaluchChiappe, EdoardoShirron, NataliNeven, PatrickArtac, MehmetKilictas, BilgesahBaranseh, JalalRubio, Elena VicenteAtci, MustafaAmato, Ottaviavan Duijnhoven, Frederieke2026-05-072026-05-072026-020960-9776http://hdl.handle.net/10400.1/28878Background: The benefit of adjuvant ovarian function suppression (OFS) and aromatase inhibitors (AI) in premenopausal patients with hormone receptor positive, HER2 positive (HR+/HER2+) breast cancer (BC) is unclear. We aimed to investigate this question in a retrospective cohort, stratified by timing (adjuvant or neoadjuvant) of chemotherapy and trastuzumab and by response to neoadjuvant therapy. Methods: Patients aged <45Y at diagnosis, with stage I-III HR + HER2+ BC, treated with (neo)adjuvant chemotherapy and trastuzumab ( +/- pertuzumab) and endocrine therapy were included. LHRH-agonists and oophorectomy were considered OFS. We compared distant disease-free survival (DDFS) with tamoxifen, OFS + tamoxifen and OFS + AI in three cohorts: neoadjuvant-pathologic complete response (pCR), neoadjuvantresidual disease (RD) and adjuvant. Endocrine therapy (ET) was modeled as a time dependent covariate in cox logistic regression analyses. Results: The study included 1124 patients with median follow-up of 72.6 months (range:0-205 months). DDFS rates at 5 years were 83.9 %, 86.8 % and 92.1 % with tamoxifen, OFS + tamoxifen and OFS + AI respectively in the RD group, 94.3 %, 97.6 % and 96.5 % in the pCR group, and 94.3 %, 93.4 % and 98.6 % in the adjuvant group. OFS + AI was associated with better DDFS compared to tamoxifen in the RD group (n = 366) (multi-variable weighted HR 0.28. 95 % CI 0.11-.069, p = 0.006), but associations of ET with DDFS in the pCR (n = 307, p = 0.59) and adjuvant (n = 451, p = 0.18) cohorts were not detected. Stage III was associated with worse DDFS in all groups. Conclusion: OFS + AI were associated with better DDFS in patients with RD after neoadjuvant therapy. Our findings can assist shared decision-making on adjuvant endocrine therapy of these patients.engAdjuvant endocrine therapyAromatase inhibitorsHER2 positiveLHRH agonistsNeoadjuvantOvarian function suppressionPathological complete responseResidual diseaseTamoxifenjournal article10.1016/j.breast.2025.104669