Abstract P6-11-09: Impact of tumor subtype on clinical features, treatment, and clinical outcomes among breast cancer patients with central nervous system disease
Authors: Meier CA , Vaz-Luis I , Seah D , Macrae EM , Burstein HJ , Sohl J , Arvold ND , Winer EP , Lin NU 
Published: August 2014

Background: Breast cancer is the second most common cancer associated with brain metastases. For some patients, central nervous system (CNS) progression is the primary clinical problem, and the optimal management of these patients remains a challenge. In this study we examined the differences in clinical characteristics, the features of CNS-directed therapy, and outcomes among breast cancer patients with brain metastases according to tumor subtype.

Methods: A retrospective series of 214 breast cancer patients with brain metastases treated at the Dana-Farber Cancer Institute from 1999-2011 was identified. Tumor subtype was classified as hormone receptor (HR)+ (ER+/PR+/HER2-), triple negative (ER-/PR-/HER2-) or HER2+ (HER2+, any HR). Descriptive analysis was performed; Chi-square, Kruskal-Wallis, and Kaplan-Meier methods were used to compare clinical characteristics, CNS-directed therapy features, and outcomes between groups.

Results: Median follow-up time since CNS progression was 8 months (0-117). Median age at CNS diagnosis was 52 years (30-82). Tumor subtype distribution was as following: 35% HR+, 36% HER2+, and 29% triple negative. Table 1 represents the clinical characteristics, CNS-directed therapy features, and outcomes according to tumor subtypes. More patients with triple negative disease (32%) had CNS involvement at presentation of metastatic disease. 8% of HER2+ patients had CNS as the only site of disease. A higher proportion of patients with HER2+ disease received more than one modality of CNS directed treatment as initial therapy. These patients also received more lines of CNS-directed therapy during the entire course of their disease. The median survival time after CNS progression differed by subtype; patients with HER2+ disease had the longest median survival times.

Conclusions: Tumor subtype appears to impact clinical presentation, type and number of CNS-directed therapies, and survival among patients with breast cancer with brain metastases.

Table 1 Tumor subtype HR+ (n = 74, 35%)HER2+ (n = 78, 36%)Triple negative (n = 62, 29%)P-valueBreakdown of treatment periods 0.2011999-200334%45%29% 2004-200628%17%31% 2007-201138%38%40% Clinical features at CNS disease presentationCNS disease at presentation of metastatic disease,%1522320.052Only site of metastatic disease,%181 Time from metastatic disease until CNS disease (median, min-max; months)16 (0-113)12 (0-65)6 (0-60)&lt;0.001Type of CNS disease,%   0.004Brain only849589 Leptomeningeal disease only040 Brain and leptomeningeal disease16111 Number of CNS lesions,%   0.4141202921 2-3151413 4+625666 Unknown300 CNS-directed therapy1st CNS-directed therapy,% 0.126Surgery553 Whole brain radiotherapy725660 SRS896 Experimental drug135 More than one modality directed to CNS82721 Never received a CNS-directed therapy505 CNS-directed therapy (first and subsequent treatments combined),%    Surgery113360.003SRS154421&lt;0.001Whole brain radiotherapy8788850.866Intrathecal therapy114150.085Systemic therapy3215&lt;0.001Number of CNS-directed treatments (median, min-max)1 (0-6)2 (1-9)1 (0-5)&lt;0.001Clinical outcomesSurvival times (median, min-max; months)6 (0-83)22 (1-117)4 (0-110)&lt;0.001Events,%9697980.016

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-11-09.