Abstract P5-08-12: HER2 status remains the primary predictor of improved survival in patients with BCBM over the past 2 decades (1996-2015)
Authors: Narloch JL , Harnden K , Broadwater G , Peterson B , Hyslop T , Kirkpatrick J , Fecci P , Kim G , Blackwell KL 
Published: March 2017

BACKGROUND: Brain metastasis is a complication in advanced breast cancer (ABC) and is associated with poor prognosis. Incidence of breast cancer brain metastasis (BCBM) is increasing with advances in therapy, allowing patients to survive long enough to develop CNS metastasis. Improved outcomes have been documented in ABC over the past decades, largely related to the use of trastuzumab in HER2+ ABC. However, it remains unclear whether survival has improved in HER2- ABC in patients with BCBM. This study asks: has the improvement in systemic and radiotherapies for HER2- breast cancer impacted survival in patients with breast cancer brain metastasis.

OBJECTIVES: 1) To estimate whether date of BCBM diagnosis is associated with overall survival (OS) in patients diagnosed between 1996-2015. 2) To estimate whether OS of this patient population depends upon other demographic and clinical factors.

METHODS: This is a retrospective chart review of patients with diagnosis of BCBM between 1996-2015. Data collection includes: age at BCBM diagnosis, ethnicity, ER/PR/HER2 status, date of BCBM diagnosis, date of primary breast cancer diagnosis, date of death/last clinical follow-up, and treatment. Kaplan-Meier analysis and the log-rank test compared OS (time from diagnosis of BCBM until death or last clinical FU) between groups diagnosed in 5-year cohorts (1996-2000, 2001-2005, 2006-2010, 2011-2015). A univariate proportional hazards model was used to regress OS on date of diagnosis. A multivariate proportional hazards model was used which included the subset of patients diagnosed with BCBM in 2001 and later. This model adjusted for additional factors: race, time to development of BCBM diagnosis, age at the time of BCBM diagnosis, year of diagnosis as a continuous factor, ER, PR, while testing the significance of HER2 status. A p-value &lt; 0.05 was significant.

RESULTS: A total of 165 patients with BCBM were included in this analysis, with a median age of 53.8 (SD 13.0) at time of BCBM diagnosis. Most patients were Caucasian (66%; 109/165) or African-American (29%; 48/165). Although statistical significance was not attained, greater median overall survival was seen for patients diagnosed with BCBM in more recent 5-year cohorts (2011-2016, 9.5 months; 2006-2010, 8 months) than patients in older cohorts (2001-2006, 3.6 months; 1996-2000, 5.3 months), p=0.3. Date of diagnosis of BCBM as a continuous variable is predictive of overall survival (HR 0.83 [95% CI: 0.71-0.97] comparing 5-year intervals, p=0.016). After adjusting for the covariates listed above, HER2 positive status is predictive of overall survival (HR 0.34 [95% CI: 0.34-0.56]; p&lt;0.0001).

CONCLUSIONS: While survival has improved by 5.9 months over the past two decades, it remains highly dependent on HER2 status. Novel therapies for BCBM are greatly needed for ER+ and triple negative subtypes. Final results will include an expanded analysis to incorporate additional cases and three other categorical covariates measured during follow-up: whether the patient received radiotherapy, surgery, and/or medical therapy after diagnosis of brain metastases.

GRANT FUNDING: TL-1 CTSA Pre-Doctoral Training Grant (5TL1TR001116-03).

Citation Format: Narloch JL, Harnden K, Broadwater G, Peterson B, Hyslop T, Kirkpatrick J, Fecci P, Kim G, Blackwell KL. HER2 status remains the primary predictor of improved survival in patients with BCBM over the past 2 decades (1996-2015) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-08-12.