Fox Chase scientists identify key protein players in hard-to-treat breast cancers

At the time of diagnosis, the majority of breast cancers are categorized as estrogen-receptor positive, or hormone sensitive, which means their cancerous cells may need estrogen to grow. Patients with this type of cancer often respond favorably to treatments called aromatase inhibitors, like tamoxifen, which cause cell death by preventing estrogen from reaching the cancerous cells. Over time, however, the disease often becomes resistant to estrogen deprivation from the drugs - making treatment options more limited.

New findings that will be presented at the AACR Annual Meeting 2012 on Sunday, April 1, by researchers from Fox Chase Cancer Center in Philadelphia, identify a pair of proteins that could play a crucial role in restoring treatment sensitivity to these resistant cancerous cells - possibly leading to more treatment options in the future.

In experiments on cancer cell lines, Joan Lewis-Wambi, Ph.D., a tumor biologist at Fox Chase and lead author on the study, found that the two proteins, called STAT-1 and PLSCR-1, were 10 and 20 times more abundant respectively in breast cancer cells that are resistant to estrogen deprivation than in cancerous cells that died without estrogen. The researchers also showed that the treatment-resistant cancerous cells underwent apoptosis, or cell death, in the presence of estrogen - which suggests the hormone has a complicated relationship with breast cancer.

"Breast cancer cells that are hormone dependent need estrogen to grow," says Lewis-Wambi. "But these resistant cells have the opposite response to estrogen - instead of stimulating growth, estrogen actually induces death."

Lewis-Wambi says she and her colleagues are trying to understand the complex relationship between estrogen and the behavior of these cancerous cells. In further experiments, they found increased levels of the two proteins when estrogen caused apoptosis in the cancerous cells. Previous experiments have shown that the proteins are also associated with inteferon-alpha, a protein that promotes cell death and is often used to treat solid tumors.

The new findings suggest that a therapy that uses estrogen, along with interferon-alpha, may offer a treatment option for patients whose disease is resistant to estrogen-depriving drugs. Such a treatment may use the two proteins to successfully induce the cancerous cells to undergo cell death.

Researchers Identify Key Gene That May Be a Marker of Breast Cancer Metastasis Researchers at Fox Chase Cancer Center have identified an important gene involved in the spread of breast cancer that has developed resistance to long-term estrogen deprivation. The discovery was reported today in an oral presentation during the 97th Annual Meeting of the American Association for Cancer Research in Los Angeles. The gene may prove to be a useful marker for predicting which patients have the greatest risk of breast cancer recurrence so their doctors can offer the most appropriate treatment plan.