Changes in BMI Are Associated with Higher Distant Failure and Lower Overall Survival in Patients with Advanced Breast Cancer

Abstract

High body mass index (BMI) has been associated with worse outcomes and lower overall survival (OS) in patients (pts) with breast cancer (BC). However, this relationship is not clearly defined for those receiving neoadjuvant chemotherapy (NAC). The purpose of this study was to identify whether changes in BMI affected OS and recurrence in pts who received NAC, surgery, and radiation therapy (RT) for advanced BC. We reviewed the medical records of 112 pts with node-positive BC who received NAC at a single institution. Patients who did not receive adjuvant RT were excluded, and 83 pts were analyzed. BMI was recorded at diagnosis and 1-year after RT. Dates of local, regional, and distant failure (LF, RF, DF) were recorded. Breast cancer subtypes were defined as: luminal A (ER/PR-positive and HER2-negative, Ki-67 <16%; n=21), luminal B-like (ER/PR-positive and HER2-negative, Ki-67 > 16%; n=24), HER2-positive (ER/PR-positive or negative, HER2-positive; n=17), and triple-negative (TNBC; ER/PR-negative and HER2-negative; n=21). Time to event outcomes were evaluated using Kaplan-Meier analysis. Patients were dichotomized as losing weight (BMIΔ <0) or gaining weight/constant weight (BMIΔ ≥0). Absolute lymphocyte count (abs lymph) was recorded at the 1-year follow-up. Median follow-up was 48 months (range 12-143 months). There were 31 DF and 22 deaths. Median OS was 45 months. BMI at diagnosis was not predictive of OS or recurrence when categorized into underweight/normal (BMI <25), overweight (BMI 25-29.9), and obese (BMI ≥30). Changes in BMI did not predict for OS (p=0.12) for the general cohort, however, when analyzed by BC subtype, pts with TNBC and BMIΔ <0 showed significantly lower OS than those with BMIΔ ≥0 (p=0.03). Cumulative incidence of DF in pts with TNBC at 12 months was 33% for those with BMIΔ <0 (95% confidence interval [Cl]: 0.07-0.64), and 9% for those with BMIΔ ≥0 (Cl: 0.02-0.46). Distant failure was significantly higher in pts who lost weight across all subtypes (p=0.02); this trend was driven by pts with luminal A and TNBC (p=0.096 and p=0.07, respectively). Local and regional failures were not significantly affected by changes in BMI. When compared to pts with normal lymphocyte count, pts with lymphopenia (abs lymph <1 K/mg) had significantly worse OS and higher RF, independent of changes in BMI (p=0.003 and p=0.02, respectively). Weight loss in pts treated with NAC, surgery, and RT predicted for higher DF and worse OS, particularly in pts with TNBC. This has implications for the importance of maintaining nutrition and body weight during treatment in specific subtypes of high-risk breast cancer. The relationship between BMI and lymphopenia warrants further investigation.