Blocking the effects of estrogen (search) may offer a new way to stop lung cancer growth and reduce deaths from the disease, according to two new studies.

The results show estrogen may trigger growth in lung cancer cells (search) much in the same way that estrogen causes breast cancer cells to grow and spread.

In the first study, researchers looked at the effect of estrogen on the production of certain proteins from genes in lung cancer cells. They found that some of the same growth genes stimulated by estrogen in breast cancer are also regulated by estrogen in lung cancer.

The second study showed that combining an anti-estrogen drug currently used in treating breast cancer and another that blocks a pathway that leads to cell growth, shrank lung cancer tumors in mice by up to 59 percent.

"Our studies continue to show that lung cancer cells grow in response to estrogen and that stopping or slowing the spread of the disease may be dependent on blocking the action of estrogen," says researcher Jill Siegfried, PhD, co-leader of the Lung and Thoracic Malignancies Program at the University of Pittsburgh Cancer Institute, in a news release. "In fact, in previous studies, we have observed that lung tumor cells contain estrogen receptors at levels comparable to breast cancer cells."

Both studies appear in the Feb. 15 issue of Cancer Research.

Death rates from lung cancer in women have increased by 600 percent since 1930 in the U.S., which indicates that women may be more susceptible to the disease than men and estrogen may be the reason.

In the U.S., lung cancer is a leading cause of death in both men and women. The five-year survival is only 15 percent, although this varies with the extent of the disease. A five-year survival is what is commonly used in discussing cancer survival.

Studies have suggested that estrogen controls genes that are important to the control of lung cancer cell growth.

Combination Treatment Shows Promise

In the first study, researchers examined the effects of estrogen on the production of proteins from genes in lung cancer cells. They found that estrogen activated some of the same growth genes in lung cancer cells that are implicated in breast cancer growth.

The study also showed that an antiestrogen drug called Faslodex (search), which is commonly used in breast cancer treatment, blocked estrogen's action on lung cancer gene expression in laboratory tests.

In the second study, researchers looked at the effects of combining two therapies (Faslodex and Iressa) that target estrogen and the epidermal growth factor receptor (EGFR) in treating lung cancer tumors in mice. EGFR also acts to control cell growth and development. It is overproduced by many types of cancer and is associated with more aggressive cancers.

Iressa blocks the action of EGFR and is approved for the treatment of lung cancer after chemotherapy has failed.

This combination approach is commonly used to treat women with breast cancers that are sensitive to estrogen, otherwise known as estrogen receptor (ER) positive tumors, but it is not yet approved for treating lung cancer in humans.

The study showed that the combined treatment shrank lung cancer tumor size in mice by 59 percent, and the drugs were much more effective when given together rather than as individually.

"Evidence from our study confirms what has been described for breast cancer — that blocking the estrogen receptor and the epidermal growth factor receptor pathways together is more effective," says researcher Laura Stabile, PhD, instructor in the department of pharmacology at the University of Pittsburgh, in the news release.

Researchers say a pilot clinical trial testing this combination antiestrogen treatment is currently underway in women with advanced lung cancer.

By Jennifer Warner, reviewed by Brunilda Nazario, MD

SOURCES: Hershberger, P. Siegfried, J. Cancer Research, Feb. 15, 2005; vol 4. News release, University of Pittsburgh.