Breast Cancer Clinical Trials

• Willingness for study participation with written informed consent

• Female with age at least 18 years

• Histologically confirmed unilateral or bilateral primary invasive breast cancer

• Residual invasive disease post-neoadjuvant either in the breast or as residual nodal invasion

• Histologically confirmed hormone receptor-positive (≥1% ER and/or PR positive stained cells) and HER2-negative (IHC 2+ with FISH-negative or IHC 0-1+) assessed preferably on core biopsy of the breast or tissue from post-neoadjuvant residual invasive disease, or if no other tissue is available the residual tumor of the lymph node can be assessed. In case of bilateral breast cancer, tumor tissue of both sides needs to be assessable

• Histologically confirmed Ki67 expression assessed preferably on core biopsy or post-neoadjuvant residual invasive disease of the breast, or if not possible, of residual nodal invasion. In case of bilateral breast cancer, tumor tissue of both sides needs to be assessable

• QTc interval \< 450 msec with mean resting heart rate 50-99 beats/min (determined by ECG)

• Patients must have received neoadjuvant chemotherapy of at least 18 weeks. This period must include 6 weeks of a taxane-containing neoadjuvant therapy (Exception: For patients with progressive disease that occurred after at least 6 weeks of taxane-containing neoadjuvant treatment, a total treatment period of less than 18 weeks is also eligible)

• Adequate surgical treatment including resection of all clinically evident disease and ipsilateral axillary lymph node dissection. Histologically complete resection (R0) of the invasive and ductal in situ tumor is required in case of breast conserving surgery as the final treatment. No evidence of gross residual disease (R2) is required after total mastectomy (R1 resection is acceptable). Axillary dissection is not required in patients with a negative sentinel-node biopsy before (pN0, pN+\[mic\]) or after (ypN0, ypN+\[mic\]) neoadjuvant chemotherapy

• Less than 16 weeks interval since the date of final surgery or less than 10 weeks from completing radiotherapy (whichever occurs last) at date of randomization

• Completion of adjuvant radiotherapy according to standard guidelines (e.g. NCCN) is strongly recommended. If radiotherapy is not performed the reason for this needs to be documented in the eCRF

• No clinical evidence for locoregional or distant relapse during or after preoperative chemotherapy. Local progression during chemotherapy is not an exclusion criterion

• c/pT3N0; c/pT2N0 with MammaPrint high-risk, G3, G2+Ki67 ≥20%, or lymphovascular invasion

• Eastern Cooperative Oncology Group performance status 0 or 1

• Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCI CTCAE version 4.0 Grade ≤1 (except alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion)

• Estimated life expectancy of at least 5 years irrespective of the diagnosis of breast cancer

• The patient must be accessible for scheduled visits, treatment and follow-up. Patients registered on this trial must be treated at the participating center which could be the Principal or a Co- investigator's site