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  • Role of HER2 Status in the Treatment of Brain Metastases Arising from Breast Cancer by Stereotactic Radiosurgery

    Final Number:

    Ashwatha Narayana MD; Saroj Kunnakkat MS; Stephen Rush MD; Bernadine Donahue MD; Erik C. Parker MD; John G. Golfinos MD; Yelena Novik MD

    Study Design:

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2011 Annual Meeting

    Introduction: Over-expression of human epidermal growth factor receptor-2 (HER2) in breast cancer has been shown to be an independent risk factor of development of brain metastases (BM). However, the role of HER2 on the radio-sensitivity of BM remains controversial. We investigated the efficacy of single-fraction stereotactic radiosurgery (SRS) in the treatment of limited BM from breast cancer, based on HER2 status.

    Methods: From 2004-2010, 57 patients with limited BM were treated with SRS using Leksell Gamma-Knife to a median dose of 20 Gy (range 12-20 Gy) prescribed to the 50% isodose line. The median number of lesions treated were 2 (range 1-7) and the median tumor volume was 92.8 mm3 (range 3.4 -793.7 mm3). Over-expression of HER2 was defined as HER2 +++ by immunohistochemistry using DAKO HercepTest or fluorescence in situ hybridization (FISH). Time to local recurrence, time to development of new brain metastases, progression free survival (PFS), and overall survival (OS) were assessed from the date of SRS.

    Results: With a median follow-up of 11 months (range 1-66 months), 12 patients developed recurrence at the previously treated site (HER2 positive=9) and 30 developed new BM (HER2 positive=16) The median PFS and OS for all patients were 8 and 16 months respectively. The median PFS for HER2 positive patients compared to HER2 negative patients were 7 and 11 months, respectively (p=0.352). HER2 positive patients had a median OS of 20 months, compared to 14 months in HER2 negative patients (p=0.086). Five patients went on to develop leptomeningeal disease, all of whom were HER2 positive.

    Conclusions: HER2 over-expression does not increase the risk of recurrence at the site of treatment or appearance of new BM. It does not affect PFS or OS following SRS. However, it remains a risk factor for the development of leptomeningeal disease.

    Patient Care: This research will help improve patient care by helping to design targeted treatment to customize therapy for breast cancer.

    Learning Objectives: By the conclusion of this session, participants should be able to: 1) Understand the impact of Her2 status in the development of brain metastases. 2) Understand the role of Her2 on the outcome following treatment. 3) Design molecular targeting therapies based on the Her2 status.


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