Practicing oncologists have long appreciated that obesity is a negative prognostic factor for their patients. The epidemiology now provides vast amounts of data on just how serious the problem is.
Doctors are appreciating more and more that treating cancer effectively means treating the whole patient, not just the cancer cells. Clinical evidence is showing just how important metabolic health is to successful outcomes for patients undergoing all forms of cancer treatment.
While body mass index (BMI) is commonly used to identify obese individuals, fat distribution is actually a more precise indicator of metabolic dysfunction.
From Iyengar et al., 2016, Obesity and Cancer Mechanisms: Tumor Microenvironment and Inflammation:
“The tumor-promoting effects of obesity occur at the local level via adipose inflammation and associated alterations in the microenvironment, as well as systemically via circulating metabolic and inflammatory mediators associated with adipose inflammation. Accurately characterizing the obese state and identifying patients at increased risk for cancer development and progression will likely require more precise assessments than BMI alone. Biomarkers of adipose-tissue inflammation would help to identify high-risk populations. Moreover, adipose inflammation is a reversible process and represents a novel therapeutic target that warrants further study to break the obesity-cancer link.”
From Iwase et al., 2015, Impact of body fat distribution on neoadjuvant chemotherapy outcomes in advanced breast cancer patients:
“Obesity is known to decrease the efficacy of neoadjuvant chemotherapy (NAC) against breast cancer; however, the relationship between actual body composition and NAC outcomes remains unknown. Therefore, we determined the effect of body composition on NAC outcomes.
“A total of 172 advanced breast cancer patients who underwent surgery after NAC were retrospectively analyzed. Body composition parameters including abdominal circumference (AC), subcutaneous fat area (SFA), visceral fat area (VFA), and skeletal muscle area (SMA) were calculated using computed tomography volume-analyzing software. VFA/SFA ratio was used to evaluate visceral obesity. The associations of body composition parameters with pathological complete remission (pCR) and survival were analyzed.
“Results showed that AC, SFA and VFA were significantly correlated with BMI (all P < 0.05; r = 0.82, r = 0.71 and r = 0.78, respectively). After menopause, AC, SFA and VFA increased significantly and SMA decreased significantly (all P < 0.05). VFA/SFA ratio increased significantly after menopause, even though BMI remained unchanged. Body-composition parameters were not associated with pCR. Distant disease-free survival (DDFS) was significantly worse in the high VFA group than in the low VFA group (P < 0.05). Furthermore, in the high VFA group, postmenopausal patients had significantly shorter DDFS than premenopausal patients (P < 0.05). VFA was independently associated with DDFS in the multivariate analysis (P < 0.05). High visceral fat is associated with worse NAC outcomes in breast cancer patients, especially postmenopausal patients. Interventions targeting visceral fat accumulation will likely improve NAC outcomes.”
Mechanistically, it turns out that some of the main drivers of tumor aggressiveness and lethality are (somewhat unsurprisingly) systemic inflammation and (surprisingly) a few common hormones — insulin, leptin and adiponectin.