Purpose: The safe prerequisite of hippocampal-sparing whole brain radiotherapy (HS-WBRT) for patients with breast cancer is unclear.This study investigated the risk and relapse of perihippocampal (PH) metastases in breast cancer.Methods: Consecutive breast cancer patients with brain metastasis (BM) were reviewed.Metastases and hippocampi were contoured in cranial magnetic resonance imaging (MRI).The closest distance from metastasis to hippocampus was calculated.Clinical and radiographic variables were correlated with PH (in or within 5 mm around the hippocampus) metastasis.The risk of post-treatment PH recurrence was estimated.Results: Three hundred fourteen patients with 1,678 metastases exhibited a median breast cancer-specific overall survival (OS) and OS after BM (BMOS) of 75.4 and 14.3 months, respectively.Hippocampal metastases were identified in 1.2% of metastases and 4.1% of patients.PH lesions comprised 3.5% of lesions in 11.1% of patients.The number and aggregated volume of BM were associated with PH disease probability (univariate).Only the number of BM significantly correlated with PH disease in the multivariate analysis.The patients with PH lesions exhibited more non-oligometastatic disease, increased tumor volume, and poor BMOS.One hundred eleven patients without original PH lesions developed intracranial progression post-treatment.The risks of PH metastasis recurrence were 4.6% for WBRT and 6.8% for sub-therapeutic irradiation in the PH region.The increase in the absolute risk of PH recurrence with hippocampal-sparing irradiation was approximately 2%.Conclusions: These novel findings indicate that BM from breast cancer exhibits low risks of metastases and relapse within the hippocampal avoidance region.Non-oligometastatic disease is associated with PH metastasis.Thus, HS-WBRT is considered safe and suitable for breast cancer.