Core Viewpoint - October is Breast Cancer Awareness Month, emphasizing the importance of early prevention, detection, and treatment, particularly for HR-positive, HER2-negative advanced breast cancer patients [1][2]. Group 1: First-Line Treatment - The standard first-line treatment for HR-positive, HER2-negative advanced breast cancer is endocrine therapy combined with CDK4/6 inhibitors, which are crucial for effective tumor suppression [2]. - Endocrine therapy serves as the cornerstone of treatment, even in cases with visceral metastasis, with key drugs including tamoxifen and aromatase inhibitors [2]. - There are currently eight approved CDK4/6 inhibitors in China for HR-positive, HER2-negative breast cancer, including palbociclib and abemaciclib [2]. Group 2: Post-Resistance Strategies - Resistance to endocrine therapy does not signify the end of treatment; patients should undergo evaluations to identify the cause of resistance and find suitable alternative therapies [5]. - New treatment options are being explored, including novel CDK2/4/6 inhibitors like cumosilib, which have shown promising results in clinical trials, significantly extending progression-free survival [6][7]. - The PAM pathway (PI3K/Akt1/mTOR) is another target for therapy, with various inhibitors being developed to counteract its activation, which can lead to treatment resistance [8][9]. Group 3: Emerging Therapies - ESR1 mutations are common in patients treated with aromatase inhibitors and CDK4/6 inhibitors, leading to the development of selective estrogen receptor degraders (SERDs) as a new treatment option [10]. - Biomarkers such as HER2 and TROP2 can help identify patients who may benefit from antibody-drug conjugates (ADCs), providing targeted therapy to improve outcomes [11]. - The ongoing advancements in medical research and new drug developments offer hope for more effective treatments for HR-positive breast cancer patients [12].