Adj. Marker-adjusted Personalized Therapy Comparing ET+Ribociclib vs Chemotherapy in Intermediate Risk, HR+/HER2- EBC

The study investigates, whether the patient group with intermediate-risk early breast cancer benefits from treatment with ribociclib in combination with endocrine therapy compared to standard-of-care chemotherapy (followed by adjuvant endocrine therapy).

Inclusion Criteria: Patients eligible for inclusion in this study have to meet all of the following criteria: A. Prior to REGISTRATION in the study: 1\. Written informed consent prior to any screening procedures. 2. Female. 3. ≥ 18 years of age. 4a. EITHER: (Post)menopausal status at the time of initiation of (neo)adjuvant study medication * patient underwent bilateral oophorectomy, or * age ≥ 60, or * age \< 60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) and/or FSH and estradiol in the postmenopausal range per local normal range. 4b. OR: Pre-menopausal patients: * confirmed negative serum pregnancy test (β-hCG) before starting study treatment, or * patient has had a hysterectomy. 5. Histologically confirmed diagnosis of primary estrogen-receptor positive and/or progesterone-receptor positive (\> 1%) early breast cancer by local laboratory. 6\. Patient has HER2-negative breast cancer defined as * a negative in-situ hybridization test or an IHC status of 0, 1+, or 2+, * if IHC is 2+, a negative in-situ hybridization (FISH, CISH, or SISH) test is required (based on the most recently analyzed tissue sample and all tested by a local laboratory). 7\. Local therapy of breast cancer (if adjuvant treatment or planned if neoadjuvant treatment) according to current guidelines. Note: This may include radiotherapy of breast cancer. B. Prior to RANDOMIZATION in the study 8. No evidence of distant metastasis (confirmed prior to randomization by, preferentially, CT thorax / abdomen, X-ray chest, ultrasound liver, bone scan, or PET-CT). 9\. Patient has available tumor tissue from diagnostic biopsy. 10. Patient is classified as intermediate risk according to the ADAPT intermediate-risk definition (i) (as follows), or (only in case of missing Oncotype DX or Ki-67 response data), according to the clinical intermediate-risk definition (ii) (as follows). (i). ADAPT intermediate-risk definition: Patient meets one of the following criteria: * c/pN0, RS ≤ 25 with luminal-B-like (Ki-67 ≥20% or G3) or c/pT2-4 without endocrine response (post-endocrine Ki-67 \> 10 %) * c/pN1, RS ≤ 25 without endocrine response (post-endocrine Ki-67 \> 10 %) * c/pN0, RS \> 25 with luminal-B-like (Ki-67 ≥20% or G3) or c/pT2-4 with endocrine response (Ki-67 ≤ 10 %) * c/pN1, RS \> 25 with endocrine response (Ki-67 ≤ 10 %) * c/pN2-3, RS ≤ 25 with endocrine response (Ki-67 ≤ 10 %). Note: Postmenopausal patients with pT1-2/pN0 disease and RS \< 25, as well as premenopausal patients with pT1-2/pN0 disease and RS\ 160 or \< 90 mmHg. 17. Patient is currently receiving any of the following substances, which cannot be discontinued 7 days prior to Cycle 1 Day 1: * concomitant medications, herbal supplements, fruits (e.g. grapefruit, pomegranates, pomelos, star fruit, Seville oranges) and their juices that are strong inducers or inhibitors of CYP3A4/5, * medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5. 18. Patient is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to starting study drug, or who have not fully recovered from side effects of such treatment. 19. Participation in a prior investigational study within 30 days prior to enrollment or within five half-lives of the investigational product, whichever is longer. 20. Not able to understand and to comply with study instructions and requirements. 21. Pregnant or nursing (lactating) woman. 22. Woman of child-bearing potential defined as woman physiologically capable of becoming pregnant, unless she is using highly effective methods of contraception during the study treatment and for 21 days after stopping the treatment: * total abstinence (when this is in line with the preferred and usual lifestyle of the patient). * female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least 6 weeks before taking study treatment. * male partner sterilization (at least 6 months prior to study screening). For female patients on the study, the vasectomized male partner should be the sole partner for that patient. * placement of an intrauterine device (IUD). 23. Use of oral (estrogen and progesterone), transdermal, injected, or implanted hormonal methods of contraception as well as hormonal replacement therapy.