Body Composition, Adherence to Anthracycline and Taxane-Based Chemotherapy, and Survival After Nonmetastatic Breast Cancer

Abstract

IMPORTANCE Although most chemotherapies are dosed on body surface area or weight, body composition (ie, the amount and distribution of muscle and adipose tissues) is thought to be associated with chemotherapy tolerance and adherence.OBJECTIVES To evaluate whether body composition is associated with relative dose intensity (RDI) on anthracycline and taxane-based chemotherapy or hematologic toxic effects and whether lower RDI mediates the association of adiposity with mortality. DESIGN, SETTING, AND PARTICIPANTSAn observational cohort study with prospectively collected electronic medical record data was conducted at Kaiser Permanente Northern California, a multicenter, community oncology setting within an integrated health care delivery system. Participants included 1395 patients with nonmetastatic breast cancer diagnosed between January 1, 2005, and December 31, 2013, and treated with anthracycline and taxane-based chemotherapy. Data analysis was performed between February 25 and September 4, 2019.EXPOSURES Intramuscular, visceral, and subcutaneous adiposity as well as skeletal muscle were evaluated from clinically acquired computed tomographic scans at diagnosis. MAIN OUTCOMES AND MEASURESThe primary outcome was low RDI (<0.85), which is the ratio of delivered to planned chemotherapy dose, derived from infusion records; in addition, hematologic toxic effects were defined based on laboratory test values. To evaluate associations with overall and breast cancer-specific mortality, logistic regression models adjusted for age and body surface area were fit as well as Cox proportional hazards models adjusted for age, race/ethnicity, adiposity, Charlson comorbidity index score, and tumor stage and subtype. The mediation proportion was computed using the difference method. RESULTSThe mean (SD) age at diagnosis of the 1395 women included in the study was 52.8 (10.2) years. Greater visceral (odds ratio [OR], 1.19; 95% CI, 1.02-1.39 per SD) and intramuscular (OR, 1.16; 95% CI, 1.01-1.34 per SD) adiposity were associated with increased odds of RDI less than 0.85. Greater muscle mass was associated with a decreased odds of hematologic toxic effects (OR, 0.84; 95% CI, 0.71-0.98 per SD). Relative dose intensity less than 0.85 was associated with a 30% increased risk of death (hazard ratio, 1.30; 95% CI, 1.02-1.65). Lower RDI partially explained the association of adiposity with breast cancer-specific mortality (mediation proportion, 0.20; 95% CI, 0.05-0.55).CONCLUSIONS AND RELEVANCE Excess adiposity, presenting as larger visceral or intramuscular adiposity, was associated with lower RDI. Lower RDI partially mediated the association of adiposity with worse breast cancer-specific survival. Body composition may help to identify patients likely to experience toxic effects and subsequent dose delays or reductions, which could compromise chemotherapeutic efficacy.

Clinical Implications of Body Mass Index in Metastatic Breast Cancer Patients Treated With Abemaciclib and Endocrine Therapy

“…[4][5][6][7] In this regard, overweight and obesity, weight gain or loss during treatments, as well as muscle and adipose tissue measurements have received increasing attention as potential prognostic factors as well as predictors of treatment-related toxicities. 8,9 There is a substantial body of evidence supporting the relationship between being overweight or obese with worse outcomes in patients with early-stage BC, especially in estrogen receptor (ER)-positive BC. 10 However, in the metastatic setting, little is known and most data comes from retrospective and institutional case series, with conflicting results reported so far.…”

The Influence of Body Composition on the Systemic Exposure of Paclitaxel in Esophageal Cancer Patients

“…One example is a study in a cohort of 151 early breast cancer patients treated with anthracycline and docetaxel or paclitaxel in which patients with a low SMI had significantly more adverse events [ 16 ]. Another study correlated visceral adipose tissue with safety parameters in 1395 patients with non-metastatic breast cancer treated with an anthracycline and docetaxel and/or paclitaxel and found that patients with larger visceral adiposity had a lower cumulative dose suggesting a lower tolerability for the treatment [ 11 ]. These observations can be explained by the influence of adipose tissue on the taxane pharmacokinetic profile, and pharmacokinetics was correlated with body composition.…”

“…Skeletal muscle mass (i.e., skeletal muscle index, SMI), adipose tissue, and skeletal muscle density (SMD) (i.e., a measure for skeletal muscle quality and intramuscular fat infiltration) could potentially serve as predictive covariates, as they are associated with altered volumes of distribution, metabolism, and clearance of cytotoxic drugs [ 10 ]. Previous studies demonstrated a wide variation in muscle mass and visceral adipose tissue (VAT) in patients with identical BSA and/or body mass index (BMI), producing a heterogeneity in chemotherapy tolerance and treatment-related toxicity such as neutropenia [ 6 , 11 , 12 ].…”

Cognitive Effects and Depression Associated With Taxane-Based Chemotherapy in Breast Cancer Survivors: A Meta-Analysis

“…According to the National Cancer Institute definitions, "a person is considered to be a survivor from the time of diagnosis until the end of life" (2). Even in the era of immunotherapy and personalized medicine, chemotherapy is expected to continue to be a cornerstone in the adjuvant and neoadjuvant treatment settings, yet without treatment or prevention the debilitating side effects of chemotherapy remain (3). Up to 40% of all breast cancer survivors have lingering cognition-related complaints, sometimes known as "chemobrain" or "chemofog, " but more correctly designated chemotherapy-induced cognitive impairment (CICI).…”