Abstract 3284: Adiposity, muscle mass and delays and dose reductions on adjuvant, taxane-based chemotherapy for breast cancer
Authors: Feliciano Elizabeth M. Cespedes , Lee Valerie , Chen Wendy Y. , Prado Carla M. , Shachar Shlomit S. , Alexeeff Stacey , Caan Bette J. 
Published: August 2019

Abstract
Introduction: Low muscle mass and excess adiposity are thought to increase the risk of chemotherapy toxicity, leading to dose reductions or delays. Yet, few studies of body composition and chemotherapy examine patients with breast cancer; prior studies have been small and looked mainly at toxicities. Here, we evaluate whether adiposity or muscle mass and radiodensity (a measure of intramyocellular lipid accumulation) are associated with risk of dose reductions or delays among nonmetastatic breast cancer patients receiving adjuvant taxane-based chemotherapy, and whether dose reductions are associated with cancer-specific survival.
Methods: Our study included 1,403 patients with stage II-III breast cancer receiving taxane-based chemotherapy at Kaiser Permanente. We evaluated body composition from clinically-acquired CT scans at diagnosis. We defined dose reductions from infusion records as relative dose intensities &lt;0.85 (delivered v. planned dose) while on taxane therapy, and dose delays as treatments received more than 3 days later than scheduled. We defined neuropathy from diagnosis codes and hematologic toxicities from laboratory values during chemotherapy. Logistic regression models adjusted for age and dosing body surface area (BSA). Cox proportional hazards models for cancer-specific survival adjusted for age, BSA, body composition and tumor characteristics.
Results: Mean (standard deviation [SD]) age at diagnosis was 53 (10) years. Higher visceral adiposity was associated with a 20% increased risk of dose reductions and a 17% increased risk of dose delays on taxane-based chemotherapy (odds ratios of 1.20; 95%CI:1.02-1.42 and 1.17; 95%CI:0.99-1.39 per SD, respectively). Higher muscle radiodensity (indicating lower intramyocellular lipid infiltration, i.e., leaner muscle) was associated with a 13% lower risk of dose reductions and a 16% lower risk of dose delays (odds ratios of 0.87; 95%CI:0.75-1.00 and 0.84; 95%CI:0.72-0.98 per SD, respectively). Muscle mass and subcutaneous adiposity were not associated with dose reductions or delays, though lower muscle mass did increase risk of hematologic toxicity. Women who experienced dose reductions on taxane-based chemotherapy had a 37% increased risk of dying from breast cancer relative to those with higher relative dose intensities (hazard ratio 1.37; 95%CI:1.01-1.85; median follow-up 6 years, 203 breast cancer deaths).
Conclusions: Excess visceral adiposity and lower muscle radiodensity were associated with dose reductions and delays among breast cancer patients receiving taxane-based chemotherapy, reducing the efficacy of these life-saving therapies: women who experienced dose reductions were at higher risk of dying from breast cancer. Body composition information assessed from clinically-acquired CT scans may help identify patients for supportive interventions to mitigate toxicity.
Citation Format: Elizabeth M. Cespedes Feliciano, Valerie Lee, Wendy Y. Chen, Carla M. Prado, Shlomit S. Shachar, Stacey Alexeeff, Bette J. Caan. Adiposity, muscle mass and delays and dose reductions on adjuvant, taxane-based chemotherapy for breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3284.