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December 15, 2008
Curbing hormones in obese patients could aid against cancer

By Quinn Eastman

Once-promising drugs that were abandoned in the fight against breast cancer still could be effective in obese patients, work by Winship Cancer Institute researchers suggests.

Hormones produced by fat cells stimulate breast cancer cells to migrate and invade surrounding tissues. In laboratory tests, a class of drugs called epithelial growth factor receptor (EGFR) inhibitors could block the stimulatory effects of the hormones, oncologist Dipali Sharma and digestive disease specialist Neeraj Saxena found.

“This group of compounds was basically written off as far as breast cancer goes,” Sharma says.
Her team’s results were published online in the December issue of Cancer Research.

Obese people have high levels of leptin, a hormone produced by fat cells, and insulin-like growth factor-1 (IGF-1), which is produced primarily by the liver. Leptin sends satiety signals to the part of the brain that controls appetite, but also has several other functions such as regulating bone formation, reproductive functions and the growth of blood vessels.

“The influence of obesity on breast cancer is more pronounced because most of the breast tissue is made of adipocytes,” Sharma says. “There is an increasing amount of evidence for the importance of the environment surrounding the tumor in spurring its growth.”

Sharma and her team found that together, leptin and IGF-1 stimulate breast cancer cells to grow more than either does by itself. Acting together, they activate the EGFR molecule, the target of several anti-cancer drugs.

Various EGFR inhibitors such as erlotinib and cetuximab have been approved by the FDA to treat head and neck cancer, lung cancer, colon cancer and pancreatic cancer. One, lapatinib, was approved in 2007 for women with advanced breast cancer who had already received other therapies.

However, clinical studies did not find most EGFR inhibitors effective against breast cancer for a large enough proportion of patients for them to be approved by the FDA.

The team’s results suggest that EGFR inhibitors could be effective if directed specifically to obese patients. Sharma says the finding could be especially important for “triple negative” breast cancer, a form that does not respond to common treatments such as tamoxifen.