Age 1. Participants must be 18 years of age, or of an acceptable age according to local regulations, whichever is older, at the time of signing the informed consent.

2. Have a diagnosis of ER+, HER2- early-stage, resected, invasive breast cancer without evidence of distant metastasis a. to fulfill the requirement for ER+ disease, by local testing on primary disease specimen, tumor must express the ER by IHC, as defined in the relevant ASCO/CAP Guidelines (Allison et al. 2020) b. to fulfill the requirement of HER2- disease by local testing on primary disease specimen, tumor must be HER2- according to ASCO/CAP guidelines for HER2 testing (Wolff et al. 2018).

3. Patients with bilateral breast cancer (diagnosis of invasive tumors in both breasts simultaneously or within 6 months of each other) can be eligible if all lesions tested on both sides are ER+, HER2- (as defined in Inclusion Criterion #2) and adequate surgery has been performed in both breasts. The Lilly CRP/CRS must be consulted for all cases of bilateral breast cancer.

4. The patients must have undergone definitive loco-regional therapy (surgery, with or without radiation therapy, and/or systemic therapy where appropriate per guidelines) of the primary index breast tumor(s). a. With the exception of the situations described below, the margins of the resected specimen must be histologically free of invasive tumor and/or a component of DCIS as determined by the local pathologist. i. for patients who undergo mastectomy or wide local excision where deep margin abuts the pectoralis fascia, patients with microscopic positive margins are eligible as long as radiotherapy of the chest wall was administered. Patients with positive anterior margins may be eligible if there is no gross disease left behind (radiotherapy as per local guidelines). b. Where surgical excision of supraclavicular or internal mammary nodes is not feasible, residual nodes should have been irradiated in accordance with standard guidelines. c. If given, radiation therapy, for example, post-mastectomy or post-lumpectomy, should have been administered according to standard guidelines.

5. Patients must have received at least 24 months but not more than 60 months of any adjuvant ET, from time of adjuvant ET initiation to signing of ICF.  Neo-adjuvant endocrine therapy does not count towards the 24-60 months requirement. If a patient is experiencing AI intolerance, AI should be held during screening so that symptoms resolve prior to randomization.

6. Patients may have received (neo) adjuvant chemotherapy and/or targeted therapy with a CDK4/6- or PARP- inhibitor.

7. If patients have received either or all of the therapies indicated below (a, b), they must have completed them and have recovered (CTCAE Version 5, Grade ≤1) from the acute effects (except for residual alopecia or Grade 2 peripheral neuropathy) prior to Visit 1, with the following washout periods: a. myelosuppressive agents, for example, CDK4/6 or PARP inhibitors: At least 21 days between the last targeted therapy dose and Day 1 of treatment b. investigational agents: 28 days or 5 half-lives between the last dose of therapy and Day 1 treatment.

8. Patients must have an increased risk of disease recurrence based on clin-path risk features as defined by any of the following (a-c): a. ≥N2: ≥4 ipsilateral positive ALN b. N1: 1-3 ipsilateral positive ALN and one of the following criteria must also be present: i. tumor size ≥5 cm ii. histologic Grade 3 tumor iii. tumor size >2 cm but 2 cm but <5 cm and histologic Grade 3 

9. For female participants: both pre-/peri- and postmenopausal status is allowed. a. postmenopausal due to surgical or natural menopause requires at least 1 of the following: i. prior bilateral oophorectomy or ovarian ablation ii. age ≥60 years iii. age <60 years, amenorrheic for at least 12 months in the absence of ovarian function suppression (OFS), and FSH and estradiol levels in the postmenopausal range b. pre-/peri-menopausal patients must agree to the following: i. have a negative serum pregnancy test at baseline, within 14 days prior to Visit 1 ii. if patient is premenopausal or peri-menopausal at enrollment, agree to use OFS with any locally approved GnRH agonist (received monthly and initiated at least 28 days prior to Visit 1) if receiving study treatment with imlunestrant or an AI. Note: Participants established on a less frequent (that is, 3-month) GnRH agonist administration schedule will be permitted, if considered by the investigator to have adequate OFS based on serial estradiol and FSH assessments. iii. if patient is pre-menopausal or peri-menopausal at enrollment, agree to use highly effective, medically approved precautions to prevent pregnancy (see Section 10.4 Appendix 4) during the study and for 6 months following the last dose of study treatment.

10. If male, must agree to use the following: a. hormone suppression (initiated at least 28 days prior to Visit 1) with a locally approved GnRH agonist if receiving study treatment with imlunestrant or an AI. Monthly (preferred) or every 3-month regimens of hormone suppression are acceptable. Schedules >3 months (e.g., 6-month administration) are not permitted. b. highly effective methods of birth control and to not donate sperm during the study and for at least 6 months following the last dose of study drug(s), or for the duration specified in country requirements, whichever is longer.

11. Have a Performance Status of 0 or 1 on the Eastern Cooperative Oncology Group scale (Oken et al. 1982).

12. Have adequate organ function

13. Participants must be able to swallow capsules or tablets

14. Capable of giving signed informed consen

15. Have any evidence of a. metastatic disease (including contralateral ALN) or inflammatory breast cancer at primary breast cancer diagnosis i. inflammatory carcinoma should not apply to a patient with neglected locally advanced breast cancer presenting late in the course of their disease. 

16. Patients with more than a 6-month consecutive gap in therapy during the course of prior adjuvant ET.

17. Patients who have completed or discontinued prior adjuvant ET >6 months prior to screening. Patients who have been treated with any SERD.

18. Patients with a history of previous invasive breast cancer or an interval breast cancer (such as IDC or DCIS) that are diagnosed after the index cancer are excluded. Ipsilateral DCIS treated by definitive locoregional therapy >5 years before the index cancer is allowed. Non-invasive breast cancer neoplasia other than DCIS are allowed.

19. Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 180 days after the last dose of study intervention.

20. The patient is receiving concurrent exogenous reproductive hormone therapy, for example, birth control pills, hormone replacement therapy, or megestrol acetate. Appropriate washout period between last dose of exogenous hormone therapy and randomization is up to the investigator’s medical judgment, for example, applying 5 times the half-life elimination rule.

21. The patient has previously received ET of any duration for breast cancer prevention (tamoxifen or AIs) or raloxifene. The use of raloxifene for any indication is not allowed.

22. The patient has received an experimental treatment in a clinical trial within the last 28 days or 5 half-lives, whichever is longer, prior to randomization, or is currently enrolled in any other type of medical research (for example: medical device) judged by the Sponsor not to be scientifically or medically compatible with this study. Co-enrollment to other studies may be allowed following consultation with the Sponsor medical monitor.

23. Patients with a history of any other cancer (except non-melanoma skin cancer, Stage I uterine cancer, or carcinoma in situ of the cervix or other in-situ cancer), unless in complete remission with no therapy for a minimum of 5 years from the date of randomization. For patients with a history of other non-breast cancers within 5 years from the date of randomization and considered of very low risk of recurrence per investigator’s judgment (for example, papillary thyroid cancer treated with surgery), eligibility is to be discussed with the Sponsor medical monitor.

24. Have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study (such as preexisting medical condition of ILD/pneumonitis, severe dyspnea at rest or requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel, preexisting Crohn’s disease or ulcerative colitis, or a preexisting chronic condition resulting in clinically significant diarrhea).

25. Have had major surgery within 14 days prior to randomization.

26. Have a serious cardiac condition, such as a. cardiovascular disability defined by New York Heart Association Functional Class III and IV heart disease b. unstable angina pectoris within the last 3 months c. myocardial infarction within the last 3 months d. valvulopathy that is severe or moderate e. arrhythmias that require treatment (not including patients with rate-controlled atrial fibrillation and patients with controlled sinus tachycardia) f. cerebrovascular accident (stroke) within the last 3 months g. a mean QT interval corrected for heart rate of >470 msec on screening ECG, as calculated using the Fridericia’s formula. A grade 1 QTcF of 450–480 msec is allowed if ECG is evaluated by a cardiologist or cardio-oncologist and approved h. history of VTE, for example, DVT of the leg or arm and/or PE, will be excluded. Patients with a history of venous catheter occlusion by thrombus that did NOT surround the catheter, and the lumen could be made patent by appropriate measures, for example, saline or thrombolytic agent, are not excluded.

27. Have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study

28. Have received an autologous or allogeneic stem cell transplant

29. Have active bacterial or fungal infection, or detectable viral infection, for example, HIV or viral hepatitis. Screening is required for enrollment

30. Known allergic reaction against any of the components of the study treatment.