BackgroundPatients with metastatic human epidermal growth factor receptor 2-positive breast cancer (HER2+ BC) frequently experience brain metastases (BM). We aimed to define risk factors for the development of BM in patients with HER2+ BC and to report on their outcome.MethodsThis is a retrospective analysis of patients diagnosed with HER2+ BC between January 2000 and December 2014 at Institut Jules Bordet, Belgium. Statistical analyses were conducted with SAS V.9.4 using Kaplan-Meier method and Cox regression analyses.ResultsA total of 483 patients were included of whom 108 (22.4%) developed metastases and 52 (10.8%) BM. Among 96 metastatic patients without BM at diagnosis, 40 (41.7%) developed BM in the course of their disease. In multivariate analysis, risk factors for the development of BM were age ≤40 years (HR 2.10, 95 % CI 1.02 to 4.36), tumour size >2 cm (HR 4.94, 95% CI 1.69 to 14.47), nodal involvement (HR 3.48, 95% CI 1.47 to 8.25), absence or late start (≥6 months after initial diagnosis) of adjuvant anti-HER2 treatment (HR 3.79, 95% CI 1.52 to 9.43 or HR 2.65, 95% CI 1.03 to 6.82) and the development of lung metastases as first site of relapse (HR 6.97, 95% CI 3.41 to 14.24). Twenty-two patients with HER2+ BC and BM sent to our institute for further treatment were included in the outcome analysis. Asymptomatic patients at the time of BM diagnosis showed a better overall survival than symptomatic patients (HR 0.49, 95% CI 0.25 to 0.94).ConclusionA considerable number of patients with metastatic HER2+ BC will develop BM. Screening of patients with risk factors for BM might lead to early detection and better outcome. However, randomised controlled trials examining the use of MRI as a screening method for BM in patients with metastatic BC are warranted before such an approach can be recommended.

Introduction: BC is the most common malignancy in women. HER2+ BC is the 2nd leading cause of BM after lung cancer. The prognosis of BC patients with BM is poor. Determining risk factors for the development of BM is warranted in order to establish more accurate screening for patients at risk. Material and Methods: This is a retrospective analysis of patients with HER2+ BC treated at Institut Jules Bordet, Belgium, between 2000 and 2014. Patients' charts were reviewed for disease characteristics, treatment regimens for primary and metastatic disease as well as clinical outcomes. Statistical analyses were conducted with SAS 9.4 using Cox regression analyses, log-rank test and Kaplan-Meier method. Results: A total of 506 patients with HER2+ BC were included in the analysis. Median age was 52.7 years (range, 21.5-89.2 years). In total, 138 (27.3%) were diagnosed with metastatic BC and 74 (14.6%) had BM. Among the 138 metastatic patients, 12 (8.7%) had BM as a first site of metastatic disease and 3 (2.2%) developed BM as only site of distant relapse. Median overall survival (OS) for patients with BM was 1.74 years (range, one month-3.2 years). In multivariate analysis, risk factors for the development of BM at time-point of initial BC diagnosis were de-novo metastatic disease (hazard ratio [HR] 4.46; p<0.0001), postmenopausal status (HR 16.65; p<0.0001), and adjuvant breast radiotherapy (HR 1.79; p=0.0198). Identified risk-factors for BM at the time-point of metastatic disease were postmenopausal status (HR 1.90; p=0.0464), the presence of lung metastases (HR 2.61; p=0.0004), an interval of more than one year between initial BC diagnosis and development of metastatic disease (HR 1.91; p=0.0179) and age of <40 years (HR 1.78; p=0.0353). In this cohort, biological factors such as hormone receptor status, degree of HER2 amplification and tumor grade had no impact on the development of BM both in univariate and multivariate analysis. Furthermore, the type of systemic treatment in the adjuvant or metastatic setting (chemotherapy, anti-HER2 treatment) did not modulate the risk for BM. The combination of local treatment (surgery, stereotactic radiosurgery [SRS] or whole brain radiotherapy [WBRT]) and anti-HER2 directed therapy as first-line therapy for BM was associated with an improvement in overall survival (OS) that was more pronounced for tyrosine kinase inhibitors (HR 0.13; 95% confidence interval [CI] 0.05-0.33); p<0.0001) than for trastuzumab and/or pertuzumab (HR 0.53; 95% CI 0.24-1.15; p=0.1085). Conclusion: The development of BM is a common complication in patients experiencing metastatic HER2+ BC. Until now, no imaging screening for BM is recommended in this patient population. Compared to WBRT, surgery and SRS are associated with an improvement in OS and/or less cognitive impairment. However, these treatment approaches are limited to patients with less extensive BM disease. In this context, randomized trials examining the role of MRI screening for BM in metastatic HER2+ BC with high risk features are warranted. Citation Format: Maurer C, Tulpin L, Dumitrescu C, de Azambuja E, Moreau M, Paesmans M, Nogaret J-M, Piccart M, Awada A. Risk factors for the development of brain metastases (BM) in 506 patients with HER2-positive breast cancer (HER2+ BC): A single institutional retrospective analysis [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-07-11.