ASPO Abstracts
Mechanistic determinants of frailty in breast cancer survivors
Category: Survivorship & Health Outcomes/Comparative Effectiveness Research
Conference Year: 2021
Abstract Body:
Purpose: The expected losses of bone and muscle mass with aging are accelerated by chemotherapy and
radiation, increasing frailty risks. Frailty is inversely related to cancer survivorship. Our pre-clinical studies suggest
that the enzyme beta-glucuronidase (GUSB) aids in the bioactivation of dietary polyphenols reported to prevent
age-related bone and muscle loss. We examined associations between serum GUSB activity, a biomarker of
enzyme function, and bone density and muscle mass measures in postmenopausal breast cancer survivors (n =
27; >3 months post-chemotherapy and/or radiation). Methods: Serum GUSB enzyme activity levels were
determined using a standard assay. Total body dual-energy x-ray absorptiometry scans assessed skeletal muscle
index (SMI, appendicular lean mass [kg]/ height [m2]) and areal bone mineral density (aBMD) of the total hip,
using manual region of interest selection for hip aBMD. Backward stepwise regression models assessed the
relationship between GUSB and aBMD and, separately, GUSB and SMI. Initial covariates were age, BMI (kg/m2),
log C-reactive protein (CRP). Results: The majority of participants were non-Hispanic Caucasians (74%) with a
mean age of 57 years (range, 43 to 73) and 6.1 ± 4.6 years post-diagnosis. BMI was 30.02 ± 4.36 kg/m2, aBMD
total hip 0.99 ± 0.10 mg/cm2, SMI 6.28 ± 0.59 kg/m2, and GUSB activity 0.85 ± 0.40 U/L. GUSB correlated with
SMI, with a standardized beta coefficient of 0.551 (final covariates: BMI, log CRP; Adj. R2 0.510; p < 0.01). GUSB
correlated with total hip aBMD, with a standardized beta coefficient of 0.444 (no covariates remained; Adj. R2
0.165; p < 0.05). Conclusion: Associations of GUSB activity levels with muscle and bone mass are consistent with
the postulate that low GUSB activity may be a risk factor for increased frailty, leading to worse outcomes in
postmenopausal breast cancer survivors. Further studies are required to confirm this finding, including specific
consideration of dietary polyphenol intake. Funding Sources: NIH (CA023074, CA217725)
Keywords: breast cancer, GUSB, frailty, bone mass, muscle mass