For patients with hormone receptor‑positive (HR+) and human epidermal growth factor receptor 2‑negative (HER2‑) metastatic breast cancer (mBC), the treatment choices become more complex after progression on first‑line CDK4/6 inhibitors combined with endocrine therapy. Currently, there are no guidelines that provide a unified standard protocol for this situation. Almost half of patients with mBC develop brain metastases (BMs), and once BMs occur, the survival of the patient is often significantly reduced. An anti‑angiogenic drug and chemotherapy combination of has demonstrated synergistic effects in an mBC cell line. Anti‑angiogenic drugs have shown therapeutic efficacy in the treatment of mBC, and utidelone has shown the ability to cross the blood‑brain barrier and achieve a high concentration in brain tissue in preclinical studies. The present case report describes a patient with HR⁺/HER2^‑ mBC and BMs that developed resistance to two CDK4/6 inhibitors and treatments with anthracyclines/taxanes. The patient received a fourth‑line treatment regimen combining utidelone with a small‑molecule anti‑angiogenic drug, namely apatinib or anlotinib. The patient achieved a partial response with this combined regimen, and a progression‑free survival (PFS) of 7.6 months, which was the best therapeutic outcome in the entire course of the illness. This result was superior to the second‑line treatment with nab‑paclitaxel, which resulted in a PFS of 8 months and best overall response of stable disease with slight shrinkage. The present case indicates that a combination of utidelone with apatinib/anlotinib exhibited antitumor activity in a patient with HR⁺/HER2^‑ mBC with BMs. Therefore, this combination offers a promising therapeutic option for the clinical treatment of patients with breast cancer and BMs.

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