Inclusion Criteria:

          1. Has the pathologically-confirmed diagnosis of locally recurrent or metastatic,
             hormone-receptor positive, HER2 negative Breast Cancer.

          2. Age: 18 - 75 years old, postmenopausal women.prepostmenopausal women, but should
             receive Ovary castration.

             Inclusion Criteria

          3. Cohort 1 and Cohort 2 :No prior systemic anti-cancer therapy for advanced HR+ disease.

        Cohort 3 and Cohort 4 : Patients must satisfy the following criteria for prior therapy:

          1. a) Progressed after 2 years during treatment of adjuvant therapy with an aromatase
             inhibitor if postmenopausal, or tamoxifen if pre- or perimenopausal.

             b)Progressed within 12 months of completion of adjuvant therapy with an aromatase
             inhibitor if postmenopausal, or tamoxifen if pre- or perimenopausal.

             c) Progressed while 6 month after the end of prior aromatase inhibitor therapy for
             advanced/metastatic breast cancer if postmenopausal, or prior endocrine treatment for
             advanced/metastatic breast cancer if pre- or perimenopausal.

          2. One previous line of chemotherapy for advanced/metastatic disease is allowed in
             addition to endocrine therapy.

        4. Eastern Cooperative Oncology Group [ECOG] 0-1 Measurable disease as per Response
        Evaluation Criterion in Solid Tumors[RECIST] 1.1

        5. Adequate organ and marrow function

        Exclusion Criteria

          1. Confirmed diagnosis of HER2 positive disease

          2. Patients who received any endocrine therapy as neo/adjuvant therapy for breast cancer
             are eligible. If the neo/adjuvant therapy of any endocrine therapy , the disease-free
             interval must be greater than 12 months from the completion of treatment until study
             entry.

          3. Patients who received prior treatment with any CDK4/6 inhibitor,
             everolimus,fulvestant.

          4. Clinically significant cardiovascular and cerebrovascular diseases,including but not
             limited to severe acute myocardial infarction within 6 months before enrollment,
             unstable or severe angina, Congestive heart failure (New York heart association (NYHA)
             class > 2), or ventricular arrhythmia which need medical intervention.

          5. Has known active central nervous system metastases.