Abstract P6-16-07: Predict subsequent brain metastasis in patients with metastatic breast cancer: External validation of a published nomogram and competing risk regression analysis
Authors: Genre Ludivine , Roché Henri , Ouali Monia , Filleron Thomas , Dalenc Florence 
Published: May 2015

Abstract
Backgroud: Brain metastasis (BM) is a fatal event that nontheless alter seriously survival of patients suffering from breast cancer but also reduce their quality of life. Selection of an enriched patients population at high risk for BM is warranted to develope preventive strategies and/or to evaluate the impact early treatment of BM in prospective trials.
Methods: Electronic medical records of patients, treated in the Institut Claudius Regaud, with metastatic breast cancer and without BM at stade IV diagnosis or in the first month, were retrospectively reviewed for the period between January 2005 and December 2012. We first study the Graesslin’s nomogram (J Clin Oncol., 2010; 28(12): 2032-37) characteristics in our patients. The discrimination prediction of subsequent BM was evaluated by the area under the receiver operating characteristic curve (AUC) and we performed the calibration. Moreover, we have evaluated average and maximal errors between predictions and observations obtained from the calibration curve. Then, competing risk analysis was used to identify prognostic factors with time to BM appearance and death before BM.
Results: We identified 446 patients without BM at stage IV diagnosis or in the first month, 70 of them developed subsequent BM. Young age (≤ 50 years) at the diagnosis of breast cancer (p=0.01), ductal carcinoma (p=0.02), negative status of hormone receptor (p&lt;0.0001), HER2 overexpression/ amplification (p&lt;0.0001), grade III of primary tumour (p=0.04) and number of metastatic sites (p=0.05) were significatively associated with subsequent BM. The external validation of Graesslin’s nomogram shows a good discrimination with an AUC of 0.695 [95%CI, 0.61-0.77]. The calibration is correct with an E max = 0.076 and an E avg = 0.37. Interestingly, in our study the cumulative incidence of BM is 5.48%, 12.95% and 18.15% at 1, 3 and 5 years after the diagnosis of stade IV. In contrast, the cumulative incidence of death before the diagnosis of BM is 16.08%, 43.97% and 56.40% respectively. In multivariate analysis, HER2 overexpression/amplification (p&lt;0.0001), triple negative status (p=0.027) and number of metastasis sites (p=0.037) are associated with BM, while age &gt; 50 years (p=0.015) and triple negative status (p&lt;0.001) are associated with death before the BM diagnosis.
Conclusion : We have validate the robustness of Graesslin’s nomogram to predict subsequent BM in patients with metastatic breast cancer and suggest the best utility in patients with HER2+ breast cancer, looking forward new systemic therapies to control non BM in triple negative breast carcinoma.
Citation Format: Ludivine Genre, Henri Roché, Monia Ouali, Thomas Filleron, Florence Dalenc. Predict subsequent brain metastasis in patients with metastatic breast cancer: External validation of a published nomogram and competing risk regression analysis [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-16-07.