Abstract
Metastatic breast cancer (mBC) remains a major therapeutic challenge, particularly in postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) disease. The introduction of CDK4/6 inhibitors in combination with endocrine therapy has significantly improved outcomes in these patients. We present the case of a postmenopausal woman diagnosed with HR+, HER2-negative mBC with cutaneous involvement, who was initiated on letrozole and palbociclib as first-line therapy. After ten months of treatment, she demonstrated a remarkable therapeutic response, with significant clinical and radiological improvements. This case highlights the potential benefits of CDK4/6 inhibitors combined with endocrine therapy in the management of HR+, HER2-negative metastatic breast cancer, particularly in cases with skin involvement. These agents have reshaped the therapeutic landscape, providing prolonged disease control and improved patient outcomes.