palbociclib + letrozole + fulvestrant

This is a combination regimen of three drugs—palbociclib, letrozole, and fulvestrant—used in the treatment of hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2-) advanced or metastatic breast cancer. - **Palbociclib** is an oral small molecule inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), which blocks cell cycle progression from G1 to S phase, thereby inhibiting cancer cell proliferation. - **Letrozole** is a nonsteroidal aromatase inhibitor that reduces estrogen production by inhibiting the aromatase enzyme, leading to decreased stimulation of estrogen receptor–positive tumor cells. - **Fulvestrant** is a selective estrogen receptor degrader (SERD) that binds to and accelerates degradation of the estrogen receptor, blocking its activity and reducing tumor growth driven by estrogen signaling. The combination aims to maximize endocrine blockade while directly targeting cell cycle machinery in HR+/HER2- breast cancer. Palbociclib plus letrozole or palbociclib plus fulvestrant are both approved regimens for this indication; however, all three agents together as triple therapy are not standard-of-care but have been explored in clinical research settings[7][8]. The regimen may be considered for patients with advanced disease who have progressed on prior endocrine therapies.