Benefit of chemotherapy (CT) addition to ET remains controversial in premenopausal (pre) patients (pts) with 0-3 positive LNs (N0-1) and RS ≤25. In ADAPT, excellent outcome was observed in young N0-1 pts and ET response after short-term preoperative ET and RS 12-25 with ET alone. Here, we investigate impact of age, RS, and OFS on ET response, in ADAPT and its validation in the first part of ongoing phase III ADAPTcycle trial. In ADAPT, pts with clinical high-risk HR+/HER2- EBC received 3w of induction standard ET prior to surgery or core biopsy, and then ET-alone if N0-1 and RS 0-11 or 12-25 ± post-endocrine Ki67post≤10%, or CT if Ki67post>10%. In ADAPTcycle (n=5000 to screen), N0-1 pts with RS>25 and Ki67post≤10% and N2-3 pts with RS≤25 and ET-response are randomized to (neo)adjuvant CT or AI+ribociclib. 5938 pts included (ADAPT, n=3666; Acycle, n=2272): 1975 pts ≤50y/pre, 424 pts ≤40y. ET in ≤50y/pre pts included tamoxifen (98% ADAPT, 70.4% Acycle), TAM+OFS (15.2% Acycle) and AI+OFS (14.4% Acycle); >80% of >50y or post pts had AI. Baseline ER did not differ significantly between age groups ≤40, >40-50- and >50 ys. Mean baseline RS scores were higher in pts ≤40ys, but comparable between pts aged >40-50 and >50. ET-response rates varied substantially by type of ET, age, and RS in particular if no OFS in premenopausal pts. In ADAPT, ET-response was associated with improved iDFS in all age cohorts, independent of baseline Ki67.Table: LBA14Age subgroupRS 0-25 (ADAPT/A-Cycle) Endocrine Response Ki67post<= 10% (%)RS>25 (ADAPT/A-cycle) Endocrine Response Ki67post<= 10% (%)TamTAM+ OFS*AI+ OFS*AITAMTAM+ OFS*AI+ OFS*AI≤50 years and premenopausal45.1/ 37.6%65.0%76.5%14.3/ 19.5%48.0%77.8%≤40 years37.7/ 41.7%72.2%84.6%3.9/ 14.3%44.4%69.2%41-50 years46.8/ 36.8%61.9%74.617.8/ 21.8%52.2%82.6%>50 years old or postmenopausal61.7/ 49.7%****88.6/ 85.8%21.5/ 15.2%****44.6/ 64.7%* OFS data in ADAPTCycle only, in ADAPT, only 2% AI+OFS in pts ≤50 ys ** only few pts treated by OFS in >50 ys, pre group Open table in a new tab * OFS data in ADAPTCycle only, in ADAPT, only 2% AI+OFS in pts ≤50 ys ** only few pts treated by OFS in >50 ys, pre group ET-response after TAM or AI according to RS groups was similar in both trials, but adding OFS to TAM or AI substantially improves ET-response in pre pts ≤ 50y, rendering similar results as in AI-treated post pts. ET-response assessment provides clinically relevant information for CT-decision making in pre ≤50y N0-1 pts in addition to gene expression testing.