Precision diagnosis and treatment of breast cancer in the post-CDK4/6 inhibitor era

Cyclin-dependent kinase (CDK)4/6 inhibitors plus endocrine therapy represents the standard first-line treatment for patients with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. The introduction of CDK4/6 inhibitors has significantly improved the prognosis of breast cancer patients. However, it has also brought new clinical challenges, such as disease progression and treatment resistance in many patients. Currently, there is a lack of standardized subsequent treatment options for patients whose disease progresses after CDK4/6 inhibitor combined with endocrine therapy. Endocrine therapy resistance can lead to tumor progression through estrogen receptor (ESR)-dependent or ESR-independent pathways. Novel endocrine agents have the potential to benefit breast cancer patients harboring ESR1 mutations. Patients with alterations in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway may be particularly sensitive to targeted inhibitors of this pathway. Furthermore, newly approved or investigational antibody-drug conjugate (ADC), immunotherapy-based combinations, and novel cell cycle inhibitors have demonstrated promising anti-tumor activities. Precision medicine-based combination strategies not only expand clinical treatment options but also enable physicians to make personalized treatment decisions for patients. Biomarker-driven precision therapeutic strategies have emerged as a critical area of treatment development in the post-CDK4/6 inhibitor era.