Estrogen and lung cancer

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Monday, May 29, 2006 · Last updated 11:21 a.m. PT

HEALTHBEAT: Why does lung cancer acts differently in women and men

By LAURAN NEERGAARD
AP MEDICAL WRITER

WASHINGTON -- Lung cancer acts differently in women than in men, and major
new studies are exploring if estrogen is a key reason - and whether
harnessing the hormone might help fight the No. 1 cancer killer.

The gender link may sound surprising. After all, ask women what cancer
they worry most about, and surveys show breast cancer consistently tops
the list while lung cancer is seldom mentioned.

Yet lung cancer is increasingly a women's problem. It will claim more than
162,000 lives this year, 72,000 of them women. That's more women than are
killed by breast, ovarian, uterine and cervical cancers combined.

While male deaths from lung cancer have been dropping since 1991, women's
death rates are stubbornly holding steady. Much of that difference is
attributed to gender variations in smoking, lung cancer's main cause.

But consider: Women tend to get different kinds of lung cancer than men.
While it's unclear if they're at greater risk of developing the disease,
some research suggests they may absorb more cancer-causing chemicals from
cigarettes and become sick after smoking less. Among people who never
smoked, more women than men are diagnosed with lung cancer.

On the other hand, women tend to survive lung cancer slightly better than
their male counterparts. And some of the newest lung cancer drugs, Tarceva
and Iressa, seem to work more often in women.

Teasing out the biology behind the gender differences could lead to
improved treatment for everyone, says Dr. Kathy Albain, a lung cancer
specialist at Loyola University Health System.

She is heading a National Cancer Institute-funded study that is recruiting
720 newly diagnosed lung cancer patients to examine what hormones, genes
or other molecular factors explain why lung cancer behaves differently in
men and women, smokers and nonsmokers.

"We're learning what's going on in the lung, and whether or not this is a
real thing that can be exploited for cancer treatment," she says.

Estrogen already is a leading suspect.

"We're just at the infancy" of exploring the hormone's role in lung
cancer, cautions University of Pittsburgh pharmacologist Jill Siegfried, a
pioneer in the field.

But two provocative studies are getting under way:

-Siegfried's research suggests estrogen may act as a fuel for lung tumors
just like it does for many breast tumors, and that blocking estrogen with
the same drugs that breast cancer patients use might also work in the
lungs. So a 120-patient study at Pittsburgh and the University of
California, Los Angeles, will test whether women fare better when given
the anti-estrogen drug Faslodex on top of the lung cancer drug Tarceva.

Why that combination? Estrogen receptors, or docking ports, in lung tumors
seem to switch on a cancer growth factor that Tarceva specifically
targets. The hope is to deal the tumor a double whammy by blocking both.

-The second study, involving 600 women around the country, tests an
experimental drug called Xyotax that may need estrogen to work.

Seattle-based Cell Therapeutics Inc. reformulated the older cancer drug
Taxol, covering it with a protein designed to let it reach the lungs with
fewer side effects. In three large studies, this new Xyotax didn't seem to
improve survival over older competitors - until researchers checked gender
effects. Some 45 percent of women given Xyotax survived lung cancer for a
year, compared with just 25 percent of women given standard drugs or men
given either regimen. And the women with the most estrogen in their blood
fared best.

Estrogen seems to activate an enzyme inside tumors that unlocks Xyotax's
cancer-fighting ingredient from its covering, explains Siegfried.

However all this gender-based research turns out, Siegfried hopes it
raises more awareness that lung cancer is a threat to women.

"Right now, the average woman goes in to her doctor and says, 'I have a
cough' or something, and they'll just assume it's an infection or some
noncancerous process," Siegfried says. "When really, they ought to get a
chest X-ray ... much sooner to rule out lung cancer. Because they may have
it."

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EDITOR'S NOTE - Lauran Neergaard covers health and medical issues for The
Associated Press in Washington.

On the Net:

Women's lung cancer info: http://www.womenagainstlungcancer.org

Albain's study:
http://www.swog.org/Visitors/ViewProtocolDetails.asp?ProtocolID2000

Xyotax trial: http://www.ctiseattle.com

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