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

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

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Authors and Affiliations

  1. Department of Radiation Oncology, Sidney Kimmel Medical College at Thomas Jefferson University, Sidney Kimmel Cancer Center, Bodine Center, Suite G-301, 111 South 11th Street, Philadelphia, PA, 19107, USA

    Neal S. McCall, Brittany A. Simone, Kevin Ko, Chantel Venkataraman, David W. Andrews, Pramila R. Anne’, Adam P. Dicker, Wenyin Shi & Nicole L. Simone

  2. Department of Radiation Oncology, Miami Cancer Institute at Baptist Health South Florida, Miami, FL, USA

    Minesh Mehta

  3. Division of Biostatistics, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA

    Tingting Zhan

  4. MedStar Franklin Square Medical Center, Rosedale, MD, USA

    Kamila Nowak-Choi

  5. University of Naples Federico II, Naples, Italy

    Annaisabel Rese

Authors
  1. Neal S. McCall
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  2. Brittany A. Simone
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  3. Minesh Mehta
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  4. Tingting Zhan
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  13. Nicole L. Simone
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Corresponding author

Correspondence to Nicole L. Simone.

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The authors have no conflicts of interest to disclose.

Funding

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.

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McCall, N.S., Simone, B.A., Mehta, M. et al. Onco-metabolism: defining the prognostic significance of obesity and diabetes in women with brain metastases from breast cancer. Breast Cancer Res Treat 172, 221–230 (2018). https://doi.org/10.1007/s10549-018-4880-1

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