Estrogen and Lung Cancer

By Ingfei Chen

Hormonal Impact

A class of breast cancer drugs may counter lung cancer

By Ingfei Chen

Strange as it may seem, recent research shows that estrogen, which stokes the growth of most breast cancers, also spurs lung cancer cells to multiply. That may be good news because potent breast cancer drugs that sabotage the disease's hormonal fuel supply might work in the lungs too.

Lung cancer is the deadliest malignancy, killing more Americans annually than colon, prostate and breast tumors combined. Since 1930, the number of women dying from lung cancer each year in the United States has soared 600 percent.

One controversial theory holds estrogen partly to blame for the disease. In 2002, researchers in Pittsburgh showed in convincing detail that both healthy and malignant lung cells make receptor proteins for estrogen. When the hormone locks into these receptors, it triggers cell growth.

Recently, to explore therapeutic implications of this phenomenon, investigators at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA) targeted an enzyme called aromatase, which helps cells manufacture estrogen from testosterone. The scientists scrutinized 53 samples of non-small cell tumors—the predominant lung cancer type—from male and female patients. Regardless of sex, more than 85 percent of the tumors churned out aromatase.

The researchers then tested whether they could short-circuit the malignant cells' ability to thrive. They used a breast cancer drug: Arimidex (anastrozole), a pill that incapacitates aromatase, squelching estrogen production. When the scientists gave the drug to mice implanted with human lung tumor cells, "in most of the animals, there was virtually no tumor growth," says UCLA oncologist Richard Pietras. He and his colleagues published their findings on Dec. 15, 2005, in the journal Cancer Research.

Given the results, anastrozole and two other aromatase inhibitors already available to treat breast cancer are "good drugs to try for lung cancer treatment" in both women and men, says Jill Siegfried, a pharmacology researcher at the University of Pittsburgh Cancer Institute. In other research, Siegfried's group has shown that another estrogen-blocking breast cancer drug, Faslodex (fulvestrant), checks lung tumor growth in mice too.

Only one in four lung cancer patients survives two years after diagnosis. Pietras and Siegfried hope to improve those statistics by including the relatively nontoxic anti-estrogen drugs in conjunction with other treatments.

The next step, they say, is to test such combos in patients. A clinical trial of Faslodex, plus the lung cancer drug Tarceva (erlotinib), is now starting at UCLA, the University of Pittsburgh and the University of Wisconsin-Madison.

Prior evidence that estrogen plays a role in lung cancer was "spotty at best," but Pietras' and Siegfried's studies are compelling, says oncologist Jyoti Patel of Northwestern University‘s Feinberg School of Medicine in Chicago. This kind of careful research at the molecular level "is so important, and it's underdone in lung cancer." Investigations into lung cancer have lagged 20 years behind breast cancer, Patel says, but progress is finally picking up.