Obesity Drives Prognosis in Women with Metastatic Breast Cancer

Obesity is an American epidemic that is linked to increased incidence of cancer, increased toxicity and worse cancer outcomes compared with their normal weight counterparts despite receiving the same therapies. Since glucose metabolism has been implicated in intracranial progression, we hypothesized that obese patients with breast cancer metastases may have worse survival. We retrospectively identified 57 patients with stage IV breast cancer with brain metastases from all subtypes of breast cancer who were treated with some form of local therapy including radiation therapy +/- surgery. Radiation was delivered as whole brain radiation (WBRT) to a median dose of 3000 cGy with a median number of 4 lesions treated, or stereotactic radiosurgery (SRS) to a median dose of 2100 cGy in a single fraction with a median number of 3 brain lesions treated. Kaplan Meier curves were generated for overall survival data and Mantel-Cox regression was performed to detect differences in groups. Median overall survival for all comers was 40 months (mos) from time of initial diagnosis. Body mass index (BMI) cutoff for overweight was 25kg/m2. Of the 57 patients included in the analysis, 24 had a BMI under 25 kg/m2 and 33 had a BMI greater than or equal to 25 kg/m2. There were 20 women with triple negative tumors, 14 with HER-2 positive tumors, 6 with ER/PR positive tumors and 10 with triple positive tumors. Tumor subtype was balanced between the two groups. Median overall survival for women with a BMI < 25 kg/m2 was 54 mos whereas in women with a BMI ≥ 25 kg/m2 this decreased to 28 mos (p=0.02). Median survival after diagnosis of brain metastases was 18.4 mos in the BMI < 25kg/m2 group versus 6.8 mos in the BMI ≥ 25kg/m2 group (p=0.001). Hazard ratio of death after diagnosis of brain metastases for women in the overweight and obese categories was 2.7 (CI: 1.239 to 5.903). Survival did not differ between groups treated with WBRT versus those treated with SRS. While the majority of tumors were triple negative, receptor status did not appear to significantly impact OS. Women were also analyzed by their breast cancer-specific graded prognostic assessment and no significant difference in survival after diagnosis of brain metastases was detected. Lastly, we attempted to quantify the effect of BMI on OS using an exponential curve fit to our data and found that increased BMI decreases survival in an exponential decay fashion (R2=0.59). Based on these data, we postulate that obesity may play in important role in the prognosis of metastatic breast cancer, specifically those patients with brain metastases. Glucose metabolism and the Warburg effect are particularly relevant in CNS disease and obesity may have a significant effect of the host’s metabolism leaving them susceptible to more aggressive disease. Innovative therapies directed at metabolism are needed to improve outcomes in metastatic breast cancer. Future work should focus on incorporating BMI in treatment decisions and outcome predictions.