A new study has reported a mechanism explaining links between obesity, inflammation, and aromatase activity in a mouse model of breast cancer. Elevated circulating estrogen levels have been linked with increased breast cancer risk in obese postmenopausal women. Aromatase activity is a process by which androgens are converted to estrogens in the body. After menopause, aromatase activity takes place primarily in adipose (fat) tissue. The resulting estrogens are then released into systemic circulation.
Necrotic adipocytes (dead fat cells) surrounded by macrophages forming crown-like structures in the mammary glands and visceral fat were observed by the authors in both mice made obese through diet and mice who became obese because of a genetic propensity to become so. Macrophages are immune cells that are involved in inflammation and scavenging of cell debris, among other activities. Most macrophages in the white fat of both obese mice and humans surround dead fat cells where they scavenge leftover contents of the cells. Obesity leads to increased fat cell death in both obese mice and humans.
The presence of crown-like structures was found to be associated with activation of nuclear factor κB (NF-κB), which plays a significant role in cell inflammation, proliferation, and apoptosis (a type of cell death initiated to rid the body of defective and other unwanted cells). In cancer cells, NF-κB promotes resistance to chemotherapy by increasing cell proliferation and inhibiting apoptosis. Inflammation associated with crown-like structures was associated in turn with heightened levels of aromatase activity in the fat of the obese mice. The authors comment that their discovery of the obesity → inflammation → aromatase axis in the mammary gland and visceral fat and its association with crown-like structures may provide insight into mechanisms underlying the increased risk of hormone receptor positive breast cancer in obese postmenopausal women, and also help explain the reduced effectiveness of aromatase inhibitors in the treatment of breast cancer in these women, and their generally worse outcomes. In short, the presence of crown-like structures may be a biomarker of increased breast cancer risk or poor prognosis.