Abstract P3-08-60: Patterns of development and prognostic factors in central nervous system metastasis according to breast cancer subtypes
Authors: Vieira IoIanda , Abreu Miguel , Alpoim Tiago , Pereira Isabel , Sousa Susana , Azevedo Isabel , Carvalho Machado , Pereira Deolinda 
Published: March 2020

Abstract
Introduction: Central nervous system (CNS) metastasis are detected in approximately 10-30% of breast cancer (BC) patients, being associated with poor prognosis despite local and systemic therapeutics available. In the current study, we aimed to evaluate the association between BC subtypes and CNS metastasis development and prognosis. Methods: Retrospective analysis of 258 BC patients’ records with pathological and/or radiological documented CNS metastasis, treated at a Cancer Center between 2003-2019, median follow-up of 61 months (range: 0-351). For analysis purpose, three BC subtypes were considered according to hormone receptor status and HER-2 expression: luminal, HER-2 positive and triple negative. Survival was evaluated by Kaplan-Meier method and groups were compared with log-rank test. Independent prognostic factors were identified using Cox regression model. A p value &lt; 0.05 was considered statistically significant. Results: Ninety four (42%) patients had HER-2 positive, 87 (39%) luminal and 41 (19%) triple negative disease. The median time between the diagnosis of BC and the detection of CNS metastasis was significantly shorter in triple negative group (18 months) compared to the others (HER-2 positive: 31 months; luminal: 54 months; p=0.001), and CNS was more often the first site of recurrence (with or without concomitant extracranial disease progression) in this group (triple negative: 25 (61%) vs. HER-2 positive: 31 (33%) vs. luminal: 27 (31%); p=0.002). Most of the patients had parenchymal metastasis (n=245), being exclusively parenchymal in 227 (88%), and 31 (12%) had leptomeningeal (LM) disease, that was isolated in 13 (5%). More than half (n=136) had multiple (&gt;3 lesions) CNS metastasis, without differences between BC subtypes. Among the patients with LM disease, 17 (68%) had luminal tumors, 5 (20%) HER2-positive and 3 (12%) triple negative (p=0.007). Forty five patients (17%) were treated with surgery for CNS metastasis, with similar proportions between BC groups. In the patients submitted to CNS surgery, the concordance between primary tumor and metastasis subtype was higher in HER-2 positive (73%) compared to 57% in triple negative and 50% in luminal groups (p=0.004). After CNS involvement, 62% (n=24) of patients with triple negative disease did not receive any systemic therapy, compared to 44% (n=37) in luminal and 33% (n=29) in HER-2 positive groups (p=0.010). Median survival after CNS metastasis documentation was longer in HER-2 positive group (27 months vs. luminal: 18 months vs. triple-negative: 14 months, p=0.004) and also in patients submitted to surgical resection of CNS metastasis (38 months vs. 6 months in other treatment modalities). In multivariate Cox regression analysis, having HER-2 positive tumor was an independent prognostic factor for increasing survival after CNS metastasis (HR 0.62, 95% CI: 0.47-0.84, p=0.002), regardless the therapeutic strategy. Conclusions: Pattern of CNS metastasis development and prognosis varies according to BC subtype. The association between LM disease and luminal tumors should be explored in future studies. Treatment modalities also play a decisive role in the prognosis of this patients, therefore, new and effective therapeutic strategies are needed.
Citation Format: IoIanda Vieira, Miguel Abreu, Tiago Alpoim, Isabel Pereira, Susana Sousa, Isabel Azevedo, Machado Carvalho, Deolinda Pereira. Patterns of development and prognostic factors in central nervous system metastasis according to breast cancer subtypes [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-60.