The American Cancer Society estimates that in 2009, 192,000 women were newly diagnosed with invasive breast cancer, and approximately 70 percent of these cases are considered to be estrogen receptor-positive (ER+), implying that estrogen and its receptor drives the disease. Also in 2009, the Society estimated that more than 40,000 women are expected to die from breast cancer - which is one breast cancer death on average every 13 minutes.

Most of the gene and proteins regulated by the estrogen receptor are unknown, and the molecular effects of therapies such as anti-hormonal drugs, like tamoxifen, are also largely unidentified, says Clarke. "This gene network ultimately regulates the choice of a cell to live or die in the face of stresses induced by endocrine therapies," he says.

To help understand the flow of signals from the estrogen receptor, Lombardi, Virginia Tech and Fox Chase Cancer Center will work as a collaborative team. Lombardi will focus on biology, examining cell cultures, mammary tumors in animals and patient breast tumors to decide ER+ molecular signaling systems, Virginia Tech scientists will build mathematical models to predict the behavior of those genes and proteins, and Fox Chase researchers will test what happens when specific genes and proteins are knocked out.

"Ultimately we will have a mathematical model to predict how the estrogen receptor system functions," Clarke says. "In the model, you can take out a gene and see how the system adjusts. That will allow us to identify good targets for therapy.

"Our part is to understand how breast cancer cells use the signaling from the estrogen receptor to survive and proliferate and make more copies of themselves and why in some tumors, you can block these signals with drugs, and they will die back, but then become resistant and grow back," says Clarke.

Source: Georgetown University Medical Center