Onco-metabolism: defining the prognostic significance of obesity and diabetes in women with brain metastases from breast cancer.
Onco-metabolism: defining the prognostic significance of obesity and diabetes in women with brain metastases from breast cancer.
- 2018
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. 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. 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. 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.
English
0167-6806
10.1007/s10549-018-4880-1 [doi] 10.1007/s10549-018-4880-1 [pii]
*Brain Neoplasms/me [Metabolism]
*Brain Neoplasms/rt [Radiotherapy]
*Breast Neoplasms/me [Metabolism]
*Breast Neoplasms/rt [Radiotherapy]
Adult
Aged
Aged, 80 and over
Brain Neoplasms/co [Complications]
Brain Neoplasms/sc [Secondary]
Breast Neoplasms/co [Complications]
Breast Neoplasms/pa [Pathology]
Diabetes Mellitus/me [Metabolism]
Diabetes Mellitus/pa [Pathology]
Diabetes Mellitus/su [Surgery]
Female
Humans
Middle Aged
Obesity/co [Complications]
Obesity/me [Metabolism]
Obesity/pa [Pathology]
Obesity/su [Surgery]
Prognosis
Radiosurgery/mt [Methods]
Treatment Outcome
MedStar Franklin Square Medical Center
Journal Article
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. 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. 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. 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.
English
0167-6806
10.1007/s10549-018-4880-1 [doi] 10.1007/s10549-018-4880-1 [pii]
*Brain Neoplasms/me [Metabolism]
*Brain Neoplasms/rt [Radiotherapy]
*Breast Neoplasms/me [Metabolism]
*Breast Neoplasms/rt [Radiotherapy]
Adult
Aged
Aged, 80 and over
Brain Neoplasms/co [Complications]
Brain Neoplasms/sc [Secondary]
Breast Neoplasms/co [Complications]
Breast Neoplasms/pa [Pathology]
Diabetes Mellitus/me [Metabolism]
Diabetes Mellitus/pa [Pathology]
Diabetes Mellitus/su [Surgery]
Female
Humans
Middle Aged
Obesity/co [Complications]
Obesity/me [Metabolism]
Obesity/pa [Pathology]
Obesity/su [Surgery]
Prognosis
Radiosurgery/mt [Methods]
Treatment Outcome
MedStar Franklin Square Medical Center
Journal Article