Background: WSG (West German Study Group)-ADAPTcycle is a prospective, multi-center, interventional, two-arm, open-label, controlled (neo)adjuvant, non-blinded, randomized phase III trial (EudraCT 2018-003749-40). It investigates whether HR+/HER2- intermediate-risk patients (pts) (about 20 % of HR+/HER2- early breast cancer, EBC) identified during screening (OncotypeDX and 3-week endocrine therapy (ET)) derive additional benefit from 2-years of the CDK4/6 inhibitor ribociclib plus ET compared to chemotherapy (CT) (followed by adjuvant ET). Co-primary endpoints are disease-free and distant disease-free survival. Methods: Starting Q1 2019 (enrollment 36 months, 80 sites), 5600 pts will be screened and 1670 randomized in a 3:2 ratio (1002 to ribociclib + ET; 668 to standard CT followed by ET). Pre-/postmenopausal pts with histologically confirmed invasive HR+/HER2- EBC at clinically enhanced risk (cT2-4 or Ki67 > 20 % or G3 or cN+) are eligible if they fulfill the ADAPT intermediate-risk group criteria: Recurrence Score (RS) ≤ 25 and poor endocrine response or RS > 25 and good endocrine response in p/cN0-1 pts or RS ≤ 25 with good endocrine response in c/pN2-3 pts. Endocrine responsiveness is determined by Ki67 response (drop to ≤ 10 %) after 3-week ET. Treatment duration is 2 years for the ribociclib + ET (premenopausal: AI + GnRH) arm and 16-24 weeks for the CT arm; treatment can be given in the neoadjuvant or adjuvant setting. 5-year follow-up consists of standard adjuvant ET. Patient reported outcomes (ePROs) are collected using CANKADO; ECG monitoring is performed using a novel CANKADO-based methodology. For translational analyses, tumor tissue will be collected at baseline (prior to ET), after 3-weeks ET (+/- 1w). Additional samples are required if residual tumor is diagnosed in case of neoadjuvant treatment and at time of recurrence. Exploratory tissue biomarker research will be conducted to assess alterations of molecular markers (e. g., ESR1, PIK3CA, CCND1, CDKN2A, RB1). Circulating DNA and tumor cells from blood samples will be used to assess mutations, gene expression, etc. Clinical trial information: 2018-003749-40.