Study Background and Disease Burden
Hormone receptor-positive (HR+), ERBB2-negative (formerly HER2-negative) breast cancer constitutes the most frequent subtype of breast malignancy, often treated successfully with endocrine therapies. However, resistance to endocrine therapy and disease progression in advanced breast cancer (ABC) remain significant clinical challenges. CDK4/6 inhibitors such as ribociclib have revolutionized treatment by substantially improving survival outcomes, as shown in the MONALEESA phase 3 clinical trials where the standard ribociclib dose was 600 mg daily. Despite these benefits, ribociclib at 600 mg is associated with dose-dependent adverse effects (AEs), notably neutropenia and QT interval prolongation, necessitating dose interruptions and reductions to maintain tolerability. Balancing efficacy with safety is critical to optimizing patient outcomes, thus raising the question whether a lower starting dose might mitigate toxicity without compromising efficacy.
