Estrogen pills can benefit women with metastatic breast cancer

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Public release date: 11-Dec-2008

http://www.eurekalert.org/pub_releases/2008-12/wuso-epc121008.php

Contact: Gwen son

ericsong@...

Washington University School of Medicine

Estrogen pills can benefit women with metastatic breast cancer

VIDEO: A new study at Washington University School of Medicine in St.

Louis has shown that estrogen therapy can shrink tumors in some women

with metastatic breast cancer. Estrogen works against...

Click here for more information.

For breast cancer survivors, the idea of taking estrogen pills is almost

a taboo. In fact, their doctors give them drugs to get rid of the

hormone because it can fuel the growth of breast cancer. So these women

would probably be surprised by the approach taken by breast cancer

physician Ellis, M.B., Ph.D., associate professor of medicine at

Washington University School of Medicine in St. Louis — he has

demonstrated that estrogen therapy can help control metastatic breast

cancer.

In a study presented at the 31st annual San Breast Cancer

Symposium, he showed that for about a third of the 66 participants —

women with metastatic breast cancer that had developed resistance to

standard estrogen-lowering therapy — a daily dose of estrogen could stop

the growth of their tumors or even cause them to shrink. The study was

funded by the Avon Foundation through the National Cancer Institute and

included six cancer centers in the United States.

Ellis believes that estrogen therapy offers an appealing alternative to

chemotherapy for metastatic breast cancer that has become resistant to

estrogen-lowering agents called aromatase inhibitors, such as

exemestane, anastrazole and letrozole. These drugs deplete the body of

estrogen and are standard treatments for hormone-receptor positive

breast cancers, which account for about 75 percent of breast cancer cases.

" By stabilizing or shrinking tumors in some women with metastatic breast

cancer, estrogen therapy can relieve pain and other symptoms of cancer

and can potentially prolong lives, " says Ellis, an oncologist with the

Siteman Cancer Center at Washington University School of Medicine and

-Jewish Hospital. " And unlike chemotherapy, estrogen enhances the

quality of life. For many of our patients, their hot flashes disappear,

and they lose other symptoms of menopause. It's a natural treatment for

breast cancer. Not only that, it's much cheaper than chemotherapy,

costing less than a dollar a day. "

Furthermore, estrogen seems able to return metastatic tumors to a

vulnerable state in which they again can be affected by aromatase

inhibitors. " We thought acquired resistance to aromatase inhibitor

therapy was permanent, " Ellis says. " But now we've shown that in some

patients giving estrogen can make it possible to cycle back to aromatase

inhibitors, and they can work again. "

About 40,000 women die of metastatic breast cancer each year, and

estrogen therapy potentially could help thousands of women with hormone

receptor-positive disease, Ellis says.

The study measured how many women with aromatase inhibitor

therapy-resistant metastatic breast cancer responded to estrogen

therapy. All study participants had estrogen-receptor positive tumors

that had spread to their bones, livers or lungs. The women were

postmenopausal with an average age of 59.

Coming into the study, all the participants were taking aromatase

inhibitors to slow or stop the growth of their tumors. But their tumors

had stopped responding to the treatment and had begun to grow again.

Half of the patients got a high dose of estrogen (30 milligrams a day)

and half got a low dose (6 milligrams a day).

Ellis points out that decades ago, high-dose synthetic estrogen was an

accepted breast cancer therapy and was only abandoned when the

estrogen-blocker tamoxifen came along in the 1970s and proved just as

effective with fewer side effects. The high dose in the current study

was based on the amount given to breast cancer patients in many of those

earlier regimens.

Both the high- and low-dose treatments led to stabilization or shrinkage

of metastatic tumors in about 30 percent of the participants. But the

high-dose regimen had significant side effects such as nausea, vomiting,

vaginal bleeding, fluid retention or calcium imbalances. In contrast,

the low-dose regimen had few side effects and was well tolerated.

The researchers found that if study participants eventually experienced

disease progression on estrogen, they could go back to an aromatase

inhibitor that they were previously resistant to and see a benefit —

their tumors were once again inhibited by estrogen deprivation. That

effect sometimes wore off after several months, but then the tumors

might again be sensitive to estrogen therapy. In fact, some patients

have cycled back and forth between estrogen and an aromatase inhibitor

for several years, thereby managing their metastatic disease.

The researchers also found that PET (positron emission tomography) scans

could predict whose tumors would respond to estrogen therapy. They

measured tumor glucose uptake before starting the women on estrogen and

again 24 hours later. The patients whose tumors showed an increased

glucose uptake, called a PET flare, were the same patients who benefited

from estrogen therapy.

It's too early to know why estrogen has a negative effect on metastatic

breast cancer tumors. But Ellis has found one clue — estrogen reduces

the amount of a tumor-promoting hormone called insulin-like growth

factor-1 (IGF1).

" I think that in order for breast cancer cells to survive in the absence

of estrogen (when patients are on aromatase inhibitors), the cells have

to learn to alter their cellular programs to utilize alternative growth

signals like IGF1, " Ellis says. " In theory, when you give estrogen back,

IGF1 decreases and cancer cells die as a consequence. But surviving

cancer cells prefer to switch back to living on estrogen — to them it's

like eating out at Mc's every day instead of foraging on roots and

berries. These cells eventually reappear as estrogen dependent tumors

and the cycle starts over. "

Ellis plans to continue to follow metastatic breast cancer patients to

quantify the response rate to retreatment with aromatase inhibitors when

estrogen therapy stops working.

--

ne Holden, MS, RD

" Ask the Parkinson Dietitian " http://www.parkinson.org/

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