Culmerciclib Plus Anlotinib and Endocrine Therapy for HR-Positive/HER2-Negative Metastatic Breast Cancer With Brain Metastases

Inclusion Criteria: * Women aged ≥ 18 years * ECOG PS of 0-1 * Life expectancy of at least 12 weeks * histologically or cytologically documented HR+/HER2- breast cancer * radiologically confirmed brain parenchymal metastases without the need for immediate local therapy * measurable brain metastasis lesion according to RANO-BM criteria * Must have active brain metastases, defined as newly diagnosed brain metastases or progressive brain metastases following prior local therapy * Prior systemic therapy must meet all the following criteria： 1. No more than 3 lines of prior systemic therapy for advanced disease 2. No more than 1 line of chemotherapy or antibody-drug conjugate (ADC) administered in the advanced setting 3. No prior CDK4/6 inhibitor therapy for advanced disease, or only 1 line of CDK4/6 inhibitor therapy with treatment duration \> 6 months * Adequate hematological, hepatic and renal function * Women of child bearing potential must agree to use a contraceptive method during the treatment period and for at least 180 days after the last dose of experiment treatment * Patients must be able to participate and comply with treatment and follow-up Exclusion Criteria: * Patients with leptomeningeal metastases, brainstem metastases or skull metastases * Prior receipt of anti-angiogenic agents or Culmerciclib * Unresolved Grade ≥2 toxicities (per CTCAE Version 6.0) attributable to any prior therapy, except alopecia * Patients with visceral crisis,defined as severe organ dysfunction assessed by symptoms, signs, laboratory examinations and rapid disease progression * Inability to swallow capsules or tablets * Any severe and/or uncontrolled medical disease * Other malignancies diagnosed within 5 years, excluding cured non-melanoma skin cancer, cervical carcinoma in situ and papillary thyroid carcinoma * Radiographic evidence of tumor invasion of major vessels, or high risk of tumor invasion into major vessels resulting in life-threatening hemorrhage as assessed by the investigator * Patients with arterial or venous thromboembolic events within 6 months, such as cerebrovascular accident, deep vein thrombosis and pulmonary embolism * Participation in other anti-tumor clinical trials within 4 weeks prior to enrollment * Any other condition that the investigator considers inappropriate to participate in this trial