Effect of HER2/neu overexpression status on multidisciplinary treatment modalities including upfront or adjuvant GKS for women with breast cancer brain metastasis

Xu Zhiyuan1, Chun-Po Yen1, David Schlesinger1, Jason P. Sheehan, PhD2

1Charlottesville, United States 2Department of Neurosurgery, University of Virginia

Keywords: breast cancer, gamma knife, brain metastasis, radiosurgery, outcome

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     Hormone status is important in breast cancer.
To study the influence of HER2/neu overexpression status on efficacy of multidisciplinary treatment modalities including upfront or adjuvant GKS for brain metastases arising from breast cancer.
     Median age at diagnosis of initial breast cancer was 45 years (range, 24 – 81, mean±SD, 46.1±11.0). Median time interval from breast cancer diagnosis to CNS parenchymal metastasis was 36.5 (0 – 368) months.
     We retrospectively reviewed records of a total of 103 patients diagnosed with breast cancer and brain metastases treated at University of Virginia Gamma Knife Center between 1996 and 2011. Kaplan-Meier plot with log rank test was employed to estimate the survival time and the difference. Cox proportional hazards regression models were utilized to determine prognostic factors as follows: age at primary malignancy diagnosis, age at CNS metastasis, ER, PR, HER2/neu status, number and total volume of CNS metastases, initial distant metastasis at sites including lung, liver, bone, and brain, time interval between development of CNS metastases and GKS, primary breast cancer diagnosis and CNS metastases.
      There were 43 patients (41.7%) identified as HER2/neu+, 60 (58.3%) were HER2/neu-. All HER2/neu+ patients received Herceptin or Tykerb during the course of treatment. Overall survival after diagnosis of CNS metastasis was 27 months and 17 months in HER2/neu+ and HER2/neu- subgroups, respectively (p=0.006). Survival benefit after diagnosis of CNS metastasis was demonstrated in patients with WBRT and adjuvant GKS as compared with GKS alone (median survival: 23 vs. 14 months, log rank test, p=0.04). Multidisciplinary treatment modalities conferred substantially extended survival evidenced by median survival times in a decreasing sequence: surgical resection plus WBRT and GKS, surgical resection plus GKS, WBRT plus GKS, and GKS alone (p=0.009). On multivariate analysis, the HER2/neu+ status and KPS at CNS metastasis greater than 70 remained independent predictors of survival after adjusting for other important clinicopathologic factors.
     This was a retrospective series.
     In patients treated with upfront GKS, there was survival advantage in HER2/neu+ subgroup as compared with HER2/neu- one. Breast cancer brain metastasis patients benefit from the multidisciplinary treatment.
     HER2/neu overexpression status plays an important role in predicting survival benefit after diagnosis of CNS metastasis.


Project Roles:

X. Zhiyuan (), C. Yen (), D. Schlesinger (), J. Sheehan ()