Brain Metastases from Breast Cancer: Recursive Partitioning Analysis of Prognostic Factors Including Molecular Subtypes and Treatment

Reviewer: Geoffrey Geiger, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: October 31, 2010

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Authors: R. Le Scodan, C. Massard, L. Jouanneau, F. Coussy, M. Gutierrez, Y. Kirova, A. Labib, E. Mouret-Fourme
Institution: Institut Curie, Hopital Rene Huguenin, Saint Cloud, France; Institut Gustave Roussy, Villejuif, France; Institut Curie, Site Ulm, Paris, France


  • Approximately 20-40% of all cancer patients will develop intracranial metastases during their disease course.
  • Solid cancers of the lung and breast are two of the most common malignancies with proclivity for spread to the brain and approximately 10-15% of breast cancer patients will ultimately develop brain metastases.
    • These patients have a median survival of approximately 5 months.
  • The RTOG has published a recursive partitioning analysis (RPA) looking at three classes of patients with brain metastases:
    • Class I: KPS 70-100, age <65, metastases to brain only
      • Median survival 7.1 months
    • Class II: KPS 70-100, age > 65 OR metastases to elsewhere sites.
      • Median survival 4.2 months
    • Class III: KPS <70
      • Median survival 2.3 months
  • Treatment recommendations for patients with brain metastases can be broken down by RPA class, with whole brain radiotherapy (WBRT) alone suggested for patients with RPA class III.
    • For patients with RPA class I-II disease and a single lesion, whole brain radiation plus stereotactic radiosurgery (SRS) or resection plus whole brain radiation is suggested.
    • For patients with two or more metastases, WBRT or WBRT+SRS is suggested.
  • This investigation was designed to determine whether a disease-specific RPA analysis could be developed to prognosticate survival in metastatic breast cancer (mBC) patients using molecular subtypes and treatment parameters.

Materials and Methods

  • Investigators retrospectively examined a patient population of 190 patients, of which 130 were ultimately selected for use in developing an RPA analysis for patients treated between January 1998 and April 2006.
  • All patients had 3+ metastases and were treated with WBRT (with or without SRS).
  • Outcomes were utilized to stratify patients according to various disease and molecular characteristics to develop an RPA analysis.
  • The final RPA divisions were grouped according to their ultimate survival times.
  • Patients were ultimately analyzed utilizing seven prognostic factors: 1) Performance status; 2) Age; 3) Trastuzumab-based therapy for HER2 overexpressing tumors; 4) Triple-negative phenotype; 5) Scarff-Bloom-Richardson grade; 6) Serum LDH level and 7) Lymphocyte count at mBC diagnosis.


  • Overall survival at 6 months was 54.9%, and 35.8% at 1 year. Median overall survival was 7.43 months.
  • When patients were broken down by RTOG RPA, 82 were patients classified as class I-II and had a median survival of 9.63 months. Patients classified as RTOG RPA class III had a median overall survival of 3.52 months (p=0.0001)
  • The majority of patients were treated with 30 Gy delivered in 10 fractions.
  • The best median survival (median 19.5 months) was observed in patients with HER2-overexpressing tumors treated with trastuzumab-based therapy.
  • The worst survival (median 3.5 months) was observed in patients with HER2-overexpressing tumors not treated with trastuzumab and with lymphopenia at mBC diagnosis, or with a KPS <70 and older than 50 years, or in patients with KPS <70 with triple negative (ER-, PR-, HER2-) tumors.
  • All other patients, when considered as a single group had a median survival of 12.49 months.
  • Survival analysis was performed using the Kaplan-Meier method and a log-rank test was used to confirm significant differences between groups.

Author’s Conclusions

  • This study is the first to apply a disease-specific RPA analysis to mBC patients, and to explain survival differences between groups using molecular subtypes and treatment parameters.
  • HER2 overexpressing tumors in patients treated with trastuzumab-based therapy had the highest survival of any analyzed group with a 1-year survival of 60% and a median survival of nearly 20 months.
  • Authors separated patients into three separate groups and the prognostic score successfully predicted the outcome of a heterogeneous group of patients with mBC.
  • This information may be useful to tailor the therapy for subgroups of patients and to define homogeneous cohorts for retrospective comparison and prospective randomized trials.

Clinical Implications

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