Abstract

Abstract Background: BM are generally associated with poor prognosis and with neurological impairments making BM a major limitation of life expectancy and quality of life in MBC. Real-world data are needed in order to quantify and better characterize this special clinical situation. Here, we present data from the MBC registry of the Austrian Study Group for Medical Tumor Therapy (AGMT-MBC-Registry). Methods: The AGMT-MBC-Registry is an ongoing multicenter registry for MBC patients in Austria. Patients with available hormone receptor and HER2 status and sufficient outcome data were included in this analysis. Unadjusted, univariate overall survival (OS) probabilities were calculated by the Kaplan-Meier method and compared by the log-rank test; multivariable adjusted hazard ratios (HR) were estimated by Cox regression models. HR were estimated with diagnosis of BM as time-dependent variable. Logistic regression was performed to investigate the probability of developing BM. Multivariable analyses included the following parameters: breast cancer subtype (luminal-like vs. HER2+ vs. TNBC), age at diagnosis of metastatic disease (continuous, in Cox regression as interaction with menopausal status), DFS (de novo metastatic or ≥ 24 months vs. < 24 months), visceral disease (yes vs. no) and number of metastatic sites (1 vs 2-3 vs. ≥4) at diagnosis of metastatic disease. Results: As of 15/04/2021, 2024 patients were included in the registry. Out of 1691 evaluable patients, 306 (18.1%) had documented BM. The incidence at diagnosis of metastatic disease and the overall incidence during the course of disease was significantly higher in HER2+ (9.5% [13/137] and 36.5% [50/137]) and triple-negative tumors (11.9% [38/318] and 27.7% [88/318]) compared to luminal-like tumors (3.3% [41/1236] and 13.6% [168/1236]) (both P<0.001). Besides subtype, ≥4 metastatic sites at diagnosis of metastatic disease and age were statistically significant associated with BM in logistic regression analysis.Median time to BM calculated from the date of diagnosis of metastatic disease was 11.3 months (95%CI 9.3-13.3) in the total population with BM, 12.7 months (95%CI 7.3-16.0) in HER2+, 5.2 months (95%CI 1.8-10.3) in triple-negative and 15.4 months (95%CI 8.4-19.5) in luminal disease, respectively. Interestingly, 13.7% of patients (42/306) had BM as first metastatic site without extracranial disease. The median number of systemic therapy-lines before and after diagnosis of BM was 1 (range 0-8) and 1 (range 0-10), respectively. Most of the patients with BM (80.1%) received radiotherapy; 12.7% focal radiotherapy, 69.8% whole brain irradiation and 9.0% both types of radiotherapy (8.5% unknown). After a median follow-up of 72.3 months (95%-CI 68.6-80.0), patients with BM had a significantly shorter median OS (7.5 months) compared to patients without BM (38.4 months) both in univariate (HR 3.58; 95%CI 3.11-4.11; P<.001) and multivariable analysis (HR 3.70; 95%CI 3.18-4.32; P<.001). OS in patients with BM differed significantly between the three breast cancer subtypes with a median OS of 36.3 months (95%CI 30.5-47.9), 33.5 months (95%CI 22.9-45.5) and 13.2 months (95%CI 11.1-18.4) in luminal, HER2+ and TNBC, respectively (overall log-rank P<0.001). Similarly, the time from diagnosis of BM and death was significantly shorter in TNBC (4.1 months; 95%CI 3.4-6.3) compared to luminal (9.7 months; 95%CI 6.8-13.7) and HER2+ breast cancer (10.7 months; 95%CI 9.1-26.2) (overall log-rank P<0.001). Conclusion: Almost 20% of patients with MBC develop BM during their course of disease, with a higher incidence in HER2+ and triple-negative disease. Besides effective prevention strategies improved systemic and local therapies are needed to minimize morbidity and improve outcome in these patients. Citation Format: Simon Peter Gampenrieder, Gabriel Rinnerthaler, Christoph Tinchon, Andreas Petzer, Marij Balic, Sonja Heibl, August F Zabernigg, Daniel Egle, Margit Sandholzer, Florian Roitner, Johannes Andel, Petra Pichler, Christopher Hager, Michael Knauer, Michael Hubalek, Christian F Singer, Richard Greil. Brain metastases (BM) from breast cancer: Real-word data from the Austrian AGMT_MBC-registry [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-21-08.

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