This retrospective study analyzed risk factors influencing the time to development of brain metastases with the aim to facilitate the definition of a high-risk population among breast cancer patients. One hundred seventy-four breast cancer patients with brain metastases, treated with whole brain radiotherapy, were evaluated. Statistical analysis included hormone receptor status, HER2/neu status, tumour grading, tumour stage, young age at the time of diagnosis, adjuvant systemic treatment, palliative systemic treatment, metastatic sites (if brain metastases were not the first site of recurrence), and immunotherapy with trastuzumab. Time to development of brain metastases was significantly prolonged by systemic palliative treatment (p< or =0.0001) whereas high tumour grading (p< or =0.04) and trastuzumab therapy (p< or =0.04) significantly shortened this time span. Patients with the brain as first metastatic site, age>35 (p< or =0.001) and stage III (p< or =0.018) at the time of diagnosis had a significantly shorter time to development for brain lesions. These factors should be further validated by a prospective trial to identify a high-risk population amongst breast cancer patients and enable the development of screening programs for early detection.