Beyond an Updated Graded Prognostic Assessment (Breast GPA): A Prognostic Index and Trends in Treatment and Survival in Breast Cancer Brain Metastases From 1985 to Today

Paul W. Sperduto, Shane Mesko, Jing Li, Daniel Cagney, Ayal Aizer, Nancy U. Lin, Eric Nesbit, Tim J. Kruser, Jason Chan, Steve Braunstein, Jessica Lee, John P. Kirkpatrick, Will Breen, Paul D. Brown, Diana Shi, Helen A. Shih, Hany Soliman, Arjun Sahgal, Ryan Shanley, William SperdutoEmil Lou, Ashlyn Everett, Drexell Hunter Boggs, Laura Masucci, David Roberge, Jill Remick, Kristin Plichta, John M. Buatti, Supriya Jain, Laurie E. Gaspar, Cheng Chia Wu, Tony J.C. Wang, John Bryant, Michael Chuong, James Yu, Veronica Chiang, Toshimichi Nakano, Hidefumi Aoyama, Minesh P. Mehta

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


PURPOSE: Brain metastases are a common sequelae of breast cancer. Survival varies widely based on diagnosis-specific prognostic factors (PF). We previously published a prognostic index (Graded Prognostic Assessment [GPA]) for patients with breast cancer with brain metastases (BCBM), based on cohort A (1985-2007, n = 642), then updated it, reporting the effect of tumor subtype in cohort B (1993-2010, n = 400). The purpose of this study is to update the Breast GPA with a larger contemporary cohort (C) and compare treatment and survival across the 3 cohorts.

METHODS AND MATERIALS: A multi-institutional (19), multinational (3), retrospective database of 2473 patients with breast cancer with newly diagnosed brain metastases (BCBM) diagnosed from January 1, 2006, to December 31, 2017, was created and compared with prior cohorts. Associations of PF and treatment with survival were analyzed. Kaplan-Meier survival estimates were compared with log-rank tests. PF were weighted and the Breast GPA was updated such that a GPA of 0 and 4.0 correlate with the worst and best prognoses, respectively.

RESULTS: Median survival (MS) for cohorts A, B, and C improved over time (from 11, to 14 to 16 months, respectively; P < .01), despite the subtype distribution becoming less favorable. PF significant for survival were tumor subtype, Karnofsky Performance Status, age, number of BCBMs, and extracranial metastases (all P < .01). MS for GPA 0 to 1.0, 1.5-2.0, 2.5-3.0, and 3.5-4.0 was 6, 13, 24, and 36 months, respectively. Between cohorts B and C, the proportion of human epidermal receptor 2 + subtype decreased from 31% to 18% (P < .01) and MS in this subtype increased from 18 to 25 months (P < .01).

CONCLUSIONS: MS has improved modestly but varies widely by diagnosis-specific PF. New PF are identified and incorporated into an updated Breast GPA (free online calculator available at The Breast GPA facilitates clinical decision-making and will be useful for stratification of future clinical trials. Furthermore, these data suggest human epidermal receptor 2-targeted therapies improve clinical outcomes in some patients with BCBM.

Original languageEnglish (US)
Pages (from-to)334-343
Number of pages10
JournalInternational Journal of Radiation Oncology Biology Physics
Issue number2
StatePublished - Jun 1 2020

Bibliographical note

Funding Information:
Grant support was received from the National Institutes of Health (NIH) grant number UL1TR002494 from the National Center for Advancing Translational Sciences (NCATS). Study data were collected and managed using REDCap electronic data capture tools hosted at the University of Minnesota. In addition, the study was supported by NIH grant number P30 CA77598 using the Biostatistics and Bioinformatics Core shared resource of the Masonic Cancer Center, University of Minnesota and the NCATS. Disclosures: A.S. reports being an advisor/consultant with Abbvie, Merck, Roche, Varian (Medical Advisory Group), Elekta (Gamma Knife Icon), BrainLAB, and VieCure (Medical Advisory Board); is a board member of the International Stereotactic Radiosurgery Society (ISRS); has presented past educational seminars with Elekta AB, Accuray Inc, Varian (CNS Teaching Faculty), BrainLAB, Medtronic Kyphon; receives research grant from Elekta AB; and received travel accommodations or paid expenses by Elekta, Varian, BrainLAB. A.S. also belongs to the Elekta MR Linac Research Consortium, Elekta Spine, Oligometastases, and Linac Based SRS Consortia. M.P.M. discloses consulting relationships with IBA, Varian, Oncoceutics, Celgene, Abbvie, Astra-Zeneca, Tocagen, and Blue Earth Diagnostics, none of which pertain to the material in the manuscript. In addition, his institution has received research funding from Novocure. He also serves on the Board of Directors of Oncoceutics.

Publisher Copyright:
© 2020 Elsevier Inc.

Copyright 2021 Elsevier B.V., All rights reserved.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural


Dive into the research topics of 'Beyond an Updated Graded Prognostic Assessment (Breast GPA): A Prognostic Index and Trends in Treatment and Survival in Breast Cancer Brain Metastases From 1985 to Today'. Together they form a unique fingerprint.

Cite this