letrozole + palbociclib + pertuzumab + trastuzumab

This is a four-drug combination regimen consisting of letrozole, palbociclib, pertuzumab, and trastuzumab. It is used in the treatment of hormone receptor–positive (HR+), human epidermal growth factor receptor 2–positive (HER2+) breast cancer. - **Letrozole** is an aromatase inhibitor that reduces estrogen production, thereby inhibiting the growth of estrogen-dependent breast cancer cells. - **Palbociclib** is a small molecule inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), which blocks cell cycle progression from G1 to S phase in tumor cells. - **Pertuzumab** and **trastuzumab** are monoclonal antibodies targeting different domains on the HER2 receptor; their dual blockade provides more comprehensive inhibition of HER2 signaling pathways involved in tumor proliferation and survival[6][8]. The rationale for this combination lies in simultaneously blocking estrogen signaling, cell cycle progression, and HER2-driven oncogenic pathways—addressing multiple mechanisms that drive HR+/HER2+ breast cancers[1][2]. This regimen has been investigated as maintenance or neoadjuvant therapy for advanced or metastatic HR+/HER2+ breast cancer[1][2].