📕 Breast cancer is the most common cancer in women worldwide. Understanding the biology of this tumor is a prerequisite for selecting an appropriate treatment. Cell cycle alterations are seen in many cancers such as breast cancer. Newly popular targeted agents in breast cancer have been reported such as cyclin dependent kinase inhibitors (CDKIs) which are agents inhibiting the function of cyclin dependent kinases (CDKs) as well as Notch, Wnt, SHH (Sonic hedgehog) which have recently been reported as a novel therapeutic target in breast cancer. They are categorized as selective and non-selective inhibitors of CDK. CDKIs have been tried as monotherapy and combination therapy. Palbocyclib is now a promising CDKI used in breast cancer. Nowadays palbocyclib is designed for a phase III trial for estrogen receptor (ER) positive breast cancer after showing favorable results in progression free survival in a phase II trial. The tumor microenvironment is increasingly recognized as a significant factor in cancer treatment response. The tumor microenvironment is considered as a target for combination therapy of breast cancer.