Refractory diarrhea in a patient with metastatic breast cancer with ABCB1 polymorphism: A case report

Although abemaciclib is an essential therapy for breast cancer, approximately 80 % of patients develop diarrhea. Abemaciclib undergoes excretion by the P-glycoprotein encoded by ATP-binding cassette subfamily B member 1 (ABCB1) in the small intestine during absorption. The polymorphism of this gene is associated with adverse effects such as pancytopenia. Therefore, we report a case of refractory diarrhea in which ABCB1 polymorphisms were investigated. A Japanese 44-year-old female was diagnosed with breast cancer (estrogen receptor positive, progesterone receptor positive, and human epidermal growth factor receptor 2-negative) accompanied with bone metastasis. Although the patient was initially treated with abemaciclib, letrozole (Femara), and leuprorelin, refractory diarrhea induced by abemaciclib occurred after six days of treatment. Serum abemaciclib concentrations were measured before and after the diarrhea alleviation and the ABCB1 (3435C>T, 1236T>C, and 2677G>T/A) polymorphisms involved in delayed abemaciclib excretion were examined. ABCB1 3435C>T polymorphism was also identified. The abemaciclib concentration prior to diarrhea alleviation was higher than the mean concentration in a large-scale clinical trial (current study; 326.7 ng/mL vs a large-scale clinical trial; 169–243 ng/mL). The patient discontinued abemaciclib as it was difficult for her to continue the dose (150 mg twice daily) because of the associated diarrhea, which was alleviated thereafter. The abemaciclib concentration after diarrhea alleviation was below the detection limit of 25.0 ng/mL. ABCB1 3435C>T polymorphism may be involved in the induction of refractory diarrhea by abemaciclib and may be an objective indicator for managing abemaciclib dosage.