MedicalResearch.com Interview with
Sai-Ching Jim Yeung, MD, PhD, FACP
Professor of Medicine
The University of Texas MD Anderson Cancer Center
Department of Emergency Medicine
Department of Endocrine Neoplasia & Hormonal Disorders
Houston, Texas 77230-1402
MedicalResearch: What are the main findings of the study?
Dr. Yeung: We believe that this study has bridged a significant gap in knowledge between epidemiological data (the association of obesity and poor breast cancer prognosis) and biological mechanisms mediating the impact of obesity on cancer. This study provides an important mechanistic insight into the causal relationship between obesity and breast cancer growth.
- Direct evidence for the links between obesity-associated changes in the biological processes and hallmarks of cancer in human estrogen receptor-positive (ER+) breast cancer.
It is well known that obesity is associated epidemiologicaly with decreased survival in ER+ breast cancer patients. Although a body of experimental literature exists to suggest important roles for estrogen, insulin/IGF-1 and adipokine signaling and inflammation in the mechanisms mediating the impact of obesity on cancer, direct evidence for these mechanisms and their importance relative to one another is lacking in cancers from obese humans.
Functional transcriptomic analysis of a prospective observation cohort with treatment-naïve ER+ breast cancer samples identified the insulin/PI3K signaling and secretion of cytokines among the top biological processes involved. Many of the obesity-associated changes in biological processes can be linked to cancer hallmarks. Upstream regulator analysis identified estrogen (?-estradiol), insulin (INS1), insulin-like growth factor-1 (IGF1), and adipokines [vascular endothelial growth factor A (VEGFA), tissue necrosis factor (TNF), interleukin-6 (IL6), oncostatin-M (OSM), chemokine ligand 5 (CCL5), leptin (LEP), leukemia inhibitory factor (LIF), C-reactive protein (CRP), adiponectin (ADIPOQ), and interleukin-10 (IL10)] in mediating the impact of obesity on human ER+ breast cancer.
- Experimental evidence that obesity causes accelerated oncogene-driven ER+ breast cancer carcinogenesis.
While it is not possible to conduct a human experiment to prospectively examine the causal relationship between obesity and breast cancer, we created a transgenic mouse model with genetically induced obesity and oncogene-driven breast cancer. With this model we found strong in vivo evidence using both longitudinal experiments and cross-sectional experiments that obesity accelerated oncogene-driven breast carcinogenesis.