BACKGROUND: Palbociclib is a selective, reversible cyclin-dependent kinase 4/6 inhibitor approved for the treatment of hormone receptor--positive metastatic breast cancer in combination with an aromatase inhibitor or fulvestrant. Although palbociclib is generally well-tolerated, rare cases of hepatotoxicity have occurred in postmarketing studies. DISCUSSION: We present a female patient with metastatic breast cancer and no baseline hepatic involvement or abnormal liver function tests (LFTs) who received palbociclib and anastrozole. After 3 months of therapy, she had asymptomatic grade 3/4 hepatotoxicity, and treatment with anastrozole and palbociclib was held. After aspartate aminotransferase (AST) and alanine aminotransferase (ALT) began to normalize, anastrozole was reintroduced and then palbociclib 125 mg was restarted 3 weeks later. Markedly increased AST and ALT occurred again; treatment with palbociclib was held for 3 weeks until the LFTs resolved to grade 1, and the dose of palbociclib was subsequently reduced to 100 mg while treatment with anastrozole was continued. The 100-mg dose of palbociclib continued to cause elevated LFTs, however, so the dose was held again until the LFTs resolved to grade 1. Palbociclib was reduced to a final dose of 75 mg without further elevations. CONCLUSION: Using the Naranjo scale and timing of the elevated AST and ALT, it is probable that palbociclib was the offending agent for the patient's hepatotoxicity. Further reducing the dose of palbociclib per prescribing information recommendations proved to be an effective strategy for managing the patient's hepatotoxicity and correlated with the dose-dependent severity of AST and ALT elevations. In the future, the periodic monitoring of LFTs beyond the first month of treatment with palbociclib should be considered. [ABSTRACT FROM AUTHOR]