Targeting chronic inflammation related to obesity with exercise has the potential to improve prognosis in obese
postmenopausal breast cancer survivors. Obesity is considered a leading modifiable contributor to breast
cancer mortality worldwide due to its association with increased recurrence and decreased overall survival
rate. A central mechanism by which obesity stimulates cancer progression is through chronic, low-grade
inflammation in adipose tissue. In particular, white adipose tissue (WAT) is a metabolically complex organ
comprised of adipocytes capable of secreting adipokines and proinflammatory cytokines related to
tumorigenesis. Chronic inflammation of WAT includes accumulation of adipose tissue macrophages (ATMs).
Specifically, the ATM M1 phenotype, elevated with obesity, provides a rich source of cytokines, which are key
mediators of obesity-associated insulin resistance. Gains in fat mass and a decline in lean mass, known as
sarcopenic obesity, are observed as a treatment side effect, further contributing to the development of WAT
and subsequent elevated M1 expression. Favorably, exercise-induced changes in sarcopenic obesity lead to a
reduction in M1 ATMs, and increase in M2 ATMs known to protect against insulin resistance by attenuating
inflammation. However it is unknown what impact this may have on cancer prognosis and what forms of
exercise are most effective at reducing chronic inflammation. Our general hypothesis is that exercise designed
to target chronic inflammation and associated sarcopenic obesity will improve prognosis in obese
postmenopausal breast cancer survivors. We propose a Phase II RCT to compare the effects of two combined
aerobic and resistance exercise interventions relative to an attention control group among early-stage obese
postmenopausal breast cancer survivors who have completed primary cancer therapy. This proposal will
address the following aims: 1) determine the effects of exercise on obesity-associated chronic inflammation; 2)
examine the effects of exercise on sarcopenic obesity; 3) determine the effects of exercise on breast cancer
prognosis and to assess whether reductions in chronic inflammation are associated with breast cancer
prognosis. This study is innovative because a) we will target adipose tissue inflammatory biomarkers to
improve cancer prognosis, b) derive a mathematical model that employs measureable markers of inflammation
to predict prognosis, c) utilize a novel biopsy method to obtain deep subcutaneous abdominal adipose tissue to
address a mechanistic prognostic question, and d) employ a unique periodized, circuit-style exercise design to
reduce chronic inflammation. If the aims are achieved, findings from this study will generate new knowledge
about exercise guidelines for breast cancer survivors most likely to improve prognosis.
If you are accessing this page during weekend or evening hours, the database may currently be offline for maintenance and should operational within a few hours. Otherwise, we have been notified of this error and will be addressing it immediately.
Please contact us
if this error persists.
We apologize for the inconvenience.
- The DCCPS Team.