Palbociclib and Letrozole in Advanced Breast Cancer

Among women with previously untreated hormone-receptor–positive advanced breast cancer, the addition of the cyclin-dependent kinase inhibitor palbociclib to letrozole therapy resulted in longer progression-free survival than that with letrozole alone. Hormone-receptor–positive breast cancer represents the largest therapeutic subtype of the disease, accounting for 60 to 65% of all malignant neoplasms of the breast. For more than 50 years, the treatment of hormone-receptor–positive disease has been focused on targeting the estrogen-receptor signaling pathway. 1 However, both new and acquired resistance to hormonal blockade occurs in a large subset of these cancers, and new approaches are needed. 2 The cyclin-dependent kinases (CDKs) are a large family of serine–threonine kinases that play an important role in regulating cell-cycle progression. The interaction of cyclin D with CDK4 and CDK6 facilitates the hyperphosphorylation of the retinoblastoma (Rb) . . .