Abstract PS5-07-10: Young HOPE/JCOG2402: A Randomized Phase III Study of Response-Guided Therapy Following Neoadjuvant Endocrine Therapy to Optimize Adjuvant Treatment in Premenopausal HR+/HER2- Breast Cancer

Abstract Background: In Asia, the incidence of breast cancer (BC) is increasing, with premenopausal patients accounting for 30-40% of all cases. The TAILORx and RxPONDER trials demonstrated that premenopausal women with hormone receptor (HR)-positive/HER2-negative BC and intermediate risk (defined as node-negative with high clinical risk and Oncotype DX Recurrence Score [RS] of 16-20, node-negative with RS 21-25, or node-positive with RS ≤25) derive benefit from adding chemotherapy (CT) to endocrine therapy (ET). The ADAPT trial suggested that patients achieving endocrine response (Ki-67≤10%) after neoadjuvant endocrine therapy (NET) had excellent outcomes without CT, regardless of menopausal status. Thus, ET response may serve as a biomarker to identify premenopausal patients who could safely omit CT. We hypothesize that premenopausal HR+/HER2- BC patients with intermediate risk (pN0 with RS16-25 or pN1 with RS ≤25) who achieve an ET response after NET can safely omit CT. The Young HOPE/JCOG2402 study is a randomized, phase III, non-inferiority trial. Methods: Patients are randomized (1:1) to either an upfront surgery arm or a NET arm, stratified by clinical nodal status (cN0/cN1), histologic grade (HG 1-2 vs. 3), and institution. Key eligibility criteria include: 1) ECOG PS 0-1; 2) premenopausal status with spontaneous menstruation within 12 months; 3) ER and/or PgR-positive and HER2-negative BC with ≥10% ER expression; 4) cN0 with clinical high-risk tumor (HG 1 with 3 cm Citation Format: M. Ono, Y. Sagara, Y. Kikawa, M. Kawamura, I. Nishibuchi, M. Yoshida, Y. Koi, N. Uehiro, T. Tsukioki, Y. Tanabe, Y. Naito, H. Tsuda, N. Mitome, K. Sasaki, T. Shibata, F. Hara, T. Fujisawa, H. Iwata, T. Shien. Young HOPE/JCOG2402: A Randomized Phase III Study of Response-Guided Therapy Following Neoadjuvant Endocrine Therapy to Optimize Adjuvant Treatment in Premenopausal HR+/HER2- Breast Cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-07-10.