Abstract P1-12-08: The incidence and outcomes of brain metastases in HER2-positive metastatic breast cancer with the advent of modern anti-HER2 therapies
Authors: Strulov Shachar S , Deal AM , Vaz-Luis I , Dees EC , Carey LA , Hassett MJ , Garrett AL , Benbow JM , Hughes ME , Mounsey L , Lin N , Anders CK 
Published: March 2017

Abstract
Background: Human epidermal growth factor receptor 2 (HER2) is over-expressed in approximately 20 - 30% of breast cancers. HER2-positive breast cancers frequently metastasize to the brain. In recent years, many new drugs have been approved for HER2-positive metastatic breast cancer (MBC). In the metastatic setting, trastuzumab was approved in 2000, lapatinib 2007, and pertuzumab and ado-trastuzumab emtansine in 2012. We sought to describe the incidence, time course, and prognostic factors of BM in patients (pts) with HER2+ MBC during the time when dramatic changes in systemic therapy occurred.
Patients/methods: The study included pts with HER2-positive MBC treated at two academic hospitals: Dana Farber Cancer Institute (DFCI) (2000-2007 [DFCI-T1], 2008-2011 [DFCI-T2]) and University of North Carolina (UNC) (2012-2014). We examined the incidence of BM (at diagnosis [dx] and within 1-2 years of MBC dx). We combined the two cohorts to examine outcomes – time to BM, survival following MBC, and survival following BM – using the Kaplan Meier method and Cox regression modeling.
Results: We identified 185 (DFCI n=128, 97 diagnosed 2000-2007 and 31 diagnosed 2008-2011; UNC n=57, all diagnosed 2012-2014) pts with HER2-positive MBC. Through a median of 4 years follow-up after the MBC dx (min 2, max 11), 118 had died and 67 were censored. The median age at MBC dx was 52 (min 25, max 88), 149 (82%) were Caucasian, 88 (48%) had hormone receptor (HR) positive BC, and 67 (37%) had de-novo (i.e., non-recurrent) MBC. BM was present at the MBC dx for 8% of pts in DFCI-T1, 16 % of pts in DFCI-T2, and 16% of pts at UNC. Within 1 year of the MBC dx, BM was present in 21% of DFCI-T1, 29% in DFCI-T2, 23% of UNC pts. Within 2 years of the MBC dx, 67 (36%) pts had developed BM, of which one third (22) were diagnosed at initial MBC presentation. In unadjusted analyses, there were no differences in time to BM dx by age (p=0.2), race (p=0.1) or HR status (p=0.1). The median survival following the development of BM for all pts was 1.5 years. A multivariable model predicting survival after the MBC dx, found factors associated with shorter survival included having (vs. not having) BM at the initial MBC dx, having received (vs. not having received) adjuvant HER2-directed therapy prior to the MBC dx, and having recurrent (vs. de novo) MBC (P≤0.02 for all). Age, HR status, race and time period of MBC dx were not significant in the multivariable model.
Conclusions: Among pts diagnosed in the modern era, after new therapies became available, BM remains a common problem for pts with HER2-positive MBC. While no obvious trends in the incidence of HER2-positive MBC are suggested, conclusions regarding incidence trends should be considered hypothesis-generating until larger, population-based data become available. Nevertheless, a dx of BM early in the course of MBC treatment and prior receipt of adjuvant trastuzumab appeared to confer a more aggressive disease course. Coordinated, prospective collection of the incidence and outcomes of BM among pts with HER2-positive MBC, studies of pts who develop BM &gt;2 years after their MBC dx, and clinical trials of treatment strategies for pts with trastuzumab-resistant BM are needed.
Citation Format: Strulov Shachar S, Deal AM, Vaz-Luis I, Dees EC, Carey LA, Hassett MJ, Garrett AL, Benbow JM, Hughes ME, Mounsey L, Lin N, Anders CK. The incidence and outcomes of brain metastases in HER2-positive metastatic breast cancer with the advent of modern anti-HER2 therapies [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-12-08.