External validation of a published nomogram for prediction of brain metastasis in patients with extra-cerebral metastatic breast cancer and risk regression analysis

Background: Survival of patients with metastatic breast cancer (MBC) suffering from brain metastasis (BM) is limited and this event is usually fatal. In 2010, the Graesslin's nomogram was published in order to predict subsequent BM in patients with breast cancer (BC) with extra-cerebral metastatic disease. This model aims to select a patient population at high risk for BM and thus will facilitate the design of prevention strategies and/or the impact of early treatment of BM in prospective clinical studies.

Patients and methods: Nomogram external validation was retrospectively applied to patients with BC and later BM between January 2005 and December 2012, treated in our institution. Moreover, risk factors of BM appearance were studied by Fine and Gray's competing risk analysis.

Results: Among 492 patients with MBC, 116 developed subsequent BM. Seventy of them were included for the nomogram validation. The discrimination is good (area under curve = 0.695 [95% confidence interval, 0.61-0.77]). Risk factors of BM appearance are: human epidermal growth factor receptor 2 (HER2) overexpression/amplification, triple-negative BC and number of extra-cerebral metastatic sites (>1). With a competing risk model, we highlight the nomogram interest for HER2+ tumour subgroup exclusively.

Conclusion: Graesslin's nomogram external validation demonstrates exportability and reproducibility. Importantly, the competing risk model analysis provides additional information for the design of prospective trials concerning the early diagnosis of BM and/or preventive treatment on high risk patients with extra-cerebral metastatic BC.