Comprehensive Analysis of Spatial, Temporal and Molecular Patterns of Ribociclib Efficacy and Resistance in Advanced Breast Cancer Patients

Inclusion Criteria:

1. Indication for treatment with ribociclib in combination with endocrine therapy in thelocally advanced or 1st line metastatic therapy setting according to SmPC. (Previoustreatment with cycline dependent kinase 4/6 (CDK4/6) inhibitors is allowed in theadjuvant setting)
2. Written informed consent prior to beginning of trial specific procedures
3. Subject must be female and aged ≥ 18 years on the day of signing informed consent
4. Locally advanced or metastatic breast cancer not amenable to curative treatment
5. Patient has HER2-negative breast cancer confirmed by local laboratory defined as anegative in situ hybridization test or an immunohistochemistry (IHC) status of 0 or 1+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test isrequired to confirm the HER2-negative status (based on the most recently analyzedtissue sample tested by a local laboratory
6. Histologically confirmed estrogen receptor (ER) positive and/ or progesterone receptor (PgR) positive breast cancer determined by core biopsy according to local in-housestandard.
7. corrected QT (QTcF) interval < 450 ms
8. Adequate organ function amenable for treatment with ribociclib as assessed by locallaboratory
9. Women of childbearing potential must have a negative urine or serum pregnancy testwithin 72 h prior to study entry and be willing to use highly effective method ofcontraception for course of the trial through 21 days after the last dose of trialtreatment.
10. Patient must be willing and able to comply with scheduled visits, treatment plans,laboratory tests, and other trial procedures.

Exclusion Criteria:

1. Concurrent participation in a study with an investigational agent/device or within 14days of study entry or 5 half-lives of the respective investigational agent/device,whichever is longer
2. Patients who are not treated for advanced HR+, HER2- breast cancer in the first linetherapy setting.
3. Patient not eligible for treatment with ribociclib according to SmPC or investigator'sdiscretion
4. Patients who are pregnant or lactating.
5. Patients with existing or patients who are at significant risk of developing correctedQT interval (QTc) prolongation. This includes

• patients with long QT syndrome
• uncontrolled or significant cardiac disease, including recent myocardialinfarction, congestive heart failure, unstable angina and bradyarrhythmia
• electrolyte abnormalities

6. Patients with known hypersensitivity to the active substance of ribociclib, soya,peanut or any other of the excipients of ribociclib.
7. Patients with active systemic infections (for example, bacterial infection requiringintravenous antibiotics at time of initiating study treatment, fungal infection, ordetectable viral infection requiring systemic therapy) or viral load (such as knownhuman immunodeficiency virus positivity or with known active hepatitis B or C, forexample, hepatitis B surface antigen positive).
8. Patients with serious preexisting medical condition(s) that, in the judgment of theinvestigator, would preclude participation in this study (such as severe renalimpairment, interstitial lung disease, severe dyspnea at rest or requiring oxygentherapy, history of major surgical resection involving the stomach or small bowel, orpreexisting Crohn's disease or ulcerative colitis or a preexisting chronic conditionresulting in clinically significant diarrhea).
9. Patient who do not agree to collection of biospecimens samples (blood, stool, tissue)