A Rare Case of Palbociclib-Induced Pancolitis: Clinical Insights and Literature Review

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are now standard therapies for hormone receptor-positive (HR+), HER2-negative advanced breast cancer. While generally well tolerated, their toxicity profiles differ, with palbociclib and ribociclib more commonly associated with hematologic toxicity and abemaciclib with gastrointestinal adverse effects such as diarrhea. Severe gastrointestinal complications such as colitis remain rare, particularly with palbociclib. We report a 65-year-old woman with metastatic HR+ breast cancer who presented with a two-week history of watery diarrhea (10-12 episodes/day), abdominal cramping, and a 5-pound weight loss while receiving palbociclib, fulvestrant, and denosumab. Infectious studies were negative, and colonoscopy demonstrated moderate pancolitis. Palbociclib was discontinued and intravenous corticosteroids were initiated for suspected drug-induced colitis, resulting in rapid symptom improvement. Although biopsy later demonstrated cytomegalovirus (CMV) positivity, antiviral therapy was deferred given negative CMV PCR and complete clinical resolution. This case highlights an uncommon presentation of palbociclib-induced pancolitis and underscores the importance of careful clinical evaluation and contextual interpretation of histologic findings to avoid unnecessary treatment.