Abstract P1-14-05: Predicting Brain Metastasis in Breast Cancer Patients: Who Is at Highest Risk?

Abstract

Abstract Background: The development of brain metastases (BrM) in women with breast cancer is associated with more advanced stage at presentation (Atahan 2008), although predicting who is at greatest risk remains difficult. This study aims to determine the characteristics of those at highest risk for BrM, and characterize treatment prior to their development. Methods: A prospective database containing 4,169 breast cancer patients (pts) was retrospectively reviewed for those developing BrM between 1997 and 2007. Demographic and prognostic variables were reviewed. Controls without BrM were matched for T stage, N stage and ER status, with 2 matched controls for 44 BrM pts. Results: Forty-nine patients (1.2%) developed BrM, among whom 6 were evident at initial presentation. BrM pts overall were diagnosed at a median age of 57 y with pathologic stages I and II accounting for 33% of cases at initial presentation. Pts developed BrM at a median of 19.7 mos after diagnosis. T1/T2 tumors were present in 65% of overall cases. 21 (43%) were ER/PR negative. Among 24 sites of distant disease evident prior to BrM were 16 (66%) bone and 6 (25%) lung metastases. Univariate BrM predictors included evidence of prior non-brain metastases (p=0.0004), high nuclear grade (p=0.002), PR-negativity (p=0.005), and inflammatory breast cancer (IBC, p=0.04). Family history of breast cancer approached significance (p=0.053). On multivariable analysis for predictors, prior non-brain metastases (p=0.001), high nuclear grade (p=0.006), and IBC (p=0.01) remained significant predictors. Despite adjustment for T and N stage, univariate treatments associated with, but given prior to BrM development, were use of radiotherapy (p=0.002), chemotherapy (p=0.009), and mastectomy (vs lumpectomy, p=0.03; vs no operation, p=0.0016). The sole treatment associated on multivariable analysis was chemotherapy use (p=0.02). After BrM diagnosis, 94% had whole brain radiotherapy, 22% had chemotherapy, and 8% underwent neurosurgery. BrM pts’ median survival was 38.6 mos, while matched controls did not reach median survival in 100 mos of mean follow up. Median time from BrM diagnosis to death was 10.8 mos, with a 5 y survival of 25.6%. Conclusion: The development of BrM is associated with shorter survival in patients with breast cancer. Several clinico-pathologic factors may identify patients at greatest risk of developing BrM, even in the face of more aggressive primary therapy. Such risk factors should be considered when developing early diagnostic and therapeutic interventions for BrM, and when validating any such intervention prospectively. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-14-05.