Development of acute myeloid leukemia (AML) in two breast cancer patients undergoing treatment with long-term palbociclib: a dual case report.

BACKGROUND: Acute myeloid leukemia (AML) can develop after exposure to certain cytotoxic agents. Palbociclib, a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor used to treat hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer, is known for hematologic side effects but rarely associated with secondary hematologic malignancies. CASE DESCRIPTION: We report two cases of AML development during prolonged breast cancer treatment with palbociclib, exploring a possible association. Case 1: a 63-year-old female diagnosed with stage I estrogen receptor (ER)/progesterone receptor (PR)-positive, HER2-negative breast cancer in 2010, treated with radiation and letrozole. Metastatic recurrence in 2019 prompted initiation of letrozole and palbociclib. In 2024, she developed anemia, neutrophilia, and circulating blasts, with bone marrow biopsy confirming AML. She was treated with azacitidine and venetoclax with poor response and died in 2025 from septic shock following surgery. Case 2: a 44-year-old female diagnosed with stage II hormone receptor-negative breast cancer in 1993, treated with surgery and chemotherapy. A local recurrence in 2005 was ER/PR-positive and she received letrozole until 2013. In 2017, she developed metastases and started letrozole and palbociclib. In 2025, she presented with pancytopenia and was diagnosed with AML. She received six cycles of azacitidine and venetoclax before progression and died later the same year. CONCLUSIONS: These cases explore a possible link between prolonged palbociclib therapy and AML development, warranting further investigation and monitoring.