Characteristics and Outcomes of Patients With Breast Cancer With Leptomeningeal Metastasis

Abstract

Background Disease presentation, prognostic factors, and treatment patterns for breast cancer patients with leptomeningeal metastasis are not well-characterized. In this study, we examined patient characteristics and prognostic factors for survival after a diagnosis of leptomeningeal metastasis. Patients and Methods 318 consecutive breast cancer patients diagnosed with leptomeningeal metastasis from January 1998 to December 2013 at Memorial Sloan Kettering Cancer Center were identified. Clinico-pathologic and treatment information were obtained by retrospective review. Associations with time from leptomeningeal diagnosis to death were evaluated by Kaplan-Meier curves, log-rank tests, and Cox proportional hazard models. Results Of the 318 patients, 44% were HR+HER2−,18% HR+HER2+, 8.5% HR−HER2+, and 25.5% triple negative; 4% had missing information. The median survival was 3.5 months (95% CI: 3.0, 4.0) with 63 patients (20%) surviving greater than 1 year. Recent diagnosis (after 2006), HER2+ subtype, higher performance status, cranial only involvement, and no evidence of non-central nervous system disease were independently associated with improved survival in multivariate analysis. Conclusions Despite the improvement noted with more recent year of diagnosis, survival following a diagnosis of leptomeningeal metastasis remains poor. Similar to patients with parenchymal brain metastasis only, the survival differs among difference receptor subtypes. A closer examination to identify factors, such as introduction of new systemic therapies that may contribute to longer-term survival may provide insight to improve management of these patients. In addition, factors we identified that are associated with survival may be considered as stratification variables in the design of future randomized clinical trials in this population.

Clinicopathological and Treatment-Associated Prognostic Factors in Patients with Breast Cancer Leptomeningeal Metastases in Relation to Tumor Biology

“…Our observations are obviously limited by the retrospective nature of this study; however, as discussed, the majority of data in this clinical condition are retrospective in nature. Moreover, consistently with our findings, another retrospective study showed a longer median survival for HER2+ BC patients diagnosed with LMD after 2005 (coinciding with the use of lapatinib in the institution) compared with those diagnosed before 2005 .…”

“…Our results confirm that BC patients diagnosed with LMD have a dismal prognosis, with a median OS of 3.9 months only [16][17][18]. The major clinical characteristic impacting prognosis was ECOG PS (in the overall population, as well as in the HER2+ and HER2− cohorts separately), consistently with reports from previous studies [3,9,11,[18][19][20]. Other authors have also reported age and tumor subtype (according to HR and HER2 status) as clinical prognostic factors [11,[16][17][18], but these results were not confirmed in our study population.…”

Treatment and outcomes of patients in the Brain Metastases in Breast Cancer Network Registry

“…This was also described in a case series of patients with leptomeningeal disease [14]. In our cohort, we could confirm that invasive lobular subtype was more frequently associated with leptomeningeal disease [14,15]. The high proportion of patients with leptomeningeal disease in the group of patients with luminal tumours might also explain the short OS for luminal-like patients with BMs in our cohort.…”

Cerebral metastasis in breast cancer

“…Der Subtyp des Primärtumors hat darüber hinaus Einfluss auf das Verteilungsmuster der Hirnmetastasierung. HER2positive Tumoren scheinen häufiger in die hintere Schädelgrube (Cerebellum) zu metastasieren [12], wohingegen hormonrezeptorpositive/HER2-negative Tumoren beim leptomeningealen Befall überrepräsentiert sind [13].…”

“…PrognoseDie Überlebenszeiten nach dem Auftreten von Hirnmetastasen liegen in der bislang publizierten internationalen Literatur im Median unter einem Jahr; doch gibt es in Abhängigkeit von der Lokalisation und dem Subtyp des Primärtumors Unterschiede. Der Befall der Meningen hat die schlechteste Prognose mit einem medianen Überleben von nur 3 Monaten und einem 1-Jahres-Überleben von 20 %[13]. In der Analyse einer japanischen Kohorte haben Patientinnen mit triple-negativem Primärtumor eine schlechtere Prognose als HER2-positive Patientinnen oder Patientinnen mit HR+/HER2-negativem Primärtumor (medianes Überleben 5 Monate vs. 18 Monate vs. 9 Monate)[14].…”