Breast Cancer Research and Treatment

, Volume 172, Issue 1, pp 221–230 | Cite as

Onco-metabolism: defining the prognostic significance of obesity and diabetes in women with brain metastases from breast cancer

  • Neal S. McCall
  • Brittany A. Simone
  • Minesh Mehta
  • Tingting Zhan
  • Kevin Ko
  • Kamila Nowak-Choi
  • Annaisabel Rese
  • Chantel Venkataraman
  • David W. Andrews
  • Pramila R. Anne’
  • Adam P. Dicker
  • Wenyin Shi
  • Nicole L. SimoneEmail author
Brief Report



Metabolic dysregulation has been implicated as a molecular driver of breast cancer in preclinical studies, especially with respect to metastases. We hypothesized that abnormalities in patient metabolism, such as obesity and diabetes, may drive outcomes in breast cancer patients with brain metastases.


We retrospectively identified 84 consecutive patients with brain metastases from breast cancer treated with intracranial radiation therapy. Radiation was delivered as whole-brain radiation to a median dose of 3000 cGy or stereotactic radiosurgery to a median dose of 2100 cGy. Kaplan Meier curves were generated for overall survival (OS) data and Mantel-Cox regression was performed to detect differences in groups.


At analysis, 81 survival events had occurred and the median OS for the entire cohort was 21.7 months. Despite similar modified graded prognostic assessments, resection rates, and receptor status, BMI ≥ 25 kg/m2 (n = 45) was associated with decreased median OS (13.7 vs. 30.6 months; p < 0.001) and median intracranial progression-free survival (PFS) (7.4 vs. 10.9 months; p = 0.04) compared to patients with BMI < 25 kg/m2 (n = 39). Similar trends were observed among all three types of breast cancer. Patients with diabetes (n = 17) had decreased median OS (11.8 vs. 26.2 months; p < 0.001) and median intracranial PFS (4.5 vs. 10.3 months; p = 0.001) compared to non-diabetics (n = 67). On multivariate analysis, both BMI ≥ 25 kg/m2 [HR 2.35 (1.39–3.98); p = 0.002] and diabetes [HR 2.77 (1.454–5.274); p = 0.002] were associated with increased mortality.


Elevated BMI or diabetes may negatively impact both overall survival and local control in patients with brain metastases from breast cancer, highlighting the importance of the translational development of therapeutic metabolic interventions. Given its prognostic significance, BMI should be used as a stratification in future clinical trial design in this patient population.


Breast cancer Brain metastases Radiation Obesity Diabetes Radiosurgery 


Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest to disclose.


This study was funded in part by the National Cancer Institute through both R01-CA227479 and the Kimmel Cancer Center’s NCI Cancer Center Support Grant P30 CA056036.

Supplementary material

10549_2018_4880_MOESM1_ESM.docx (13 kb)
Supplementary material 1 (DOCX 13 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Neal S. McCall
    • 1
  • Brittany A. Simone
    • 1
  • Minesh Mehta
    • 2
  • Tingting Zhan
    • 3
  • Kevin Ko
    • 1
  • Kamila Nowak-Choi
    • 4
  • Annaisabel Rese
    • 5
  • Chantel Venkataraman
    • 1
  • David W. Andrews
    • 1
  • Pramila R. Anne’
    • 1
  • Adam P. Dicker
    • 1
  • Wenyin Shi
    • 1
  • Nicole L. Simone
    • 1
    Email author
  1. 1.Department of Radiation OncologySidney Kimmel Medical College at Thomas Jefferson University, Sidney Kimmel Cancer CenterPhiladelphiaUSA
  2. 2.Department of Radiation OncologyMiami Cancer Institute at Baptist Health South FloridaMiamiUSA
  3. 3.Division of BiostatisticsSidney Kimmel Medical College at Thomas Jefferson UniversityPhiladelphiaUSA
  4. 4.MedStar Franklin Square Medical CenterRosedaleUSA
  5. 5.University of Naples Federico IINaplesItaly

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