Estrogen's Role in Breast Cancer Can Fluctuate

FRIDAY April 15, 2011 -- Is estrogen breast cancer's friend or foe?

A recent study in the Journal of the American Medical Association, which analyzed data from the massive Women's Health Initiative, suggested the latter when it found a reduced risk of breast cancer in women who had been on short-term estrogen therapy.

This seemed to contradict years of cautions that estrogen therapy -- once widely prescribed as an antidote for the symptoms of menopause and to prevent chronic diseases -- fuels estrogen receptor-positive breast cancers.

In fact, this wily hormone can be both, according to an editorial in the April 10 issue of Cancer Prevention Research.

"Estrogen is bad at the right time, and estrogen is good at the right time," said editorial co-author V. Craig Jordan, considered the "father" of tamoxifen and other anti-estrogen treatments for breast cancer.

It's true, estrogen is necessary for cancer cells to grow and multiply, but when the cancer cells develop in an environment where estrogen hasn't been present for a while, they are killed off by an unexpected flood of the hormone, he explained.

A state of estrogen deprivation can come years after menopause, when production of estrogen naturally stops or even after a woman has been receiving anti-estrogen therapy for breast cancer.

In such a state of deprivation, Jordan said, "cells grow that are not independent of estrogen. They have learned to grow with just a little tickle of estrogen. They're hanging on with a sort of starvation diet.

"When they start to form tumors and we put back normal-dose estrogen, the cells see this as a death signal because they're suddenly given a massive concentration of high-octane fuel. It's a complete overdose. Like a starving person, you can't just say sit down and eat all you want at McDonald's because you'll kill them," added Jordan, who is scientific director of Georgetown University's Lombardi Cancer Center.

It's important to remember that estrogen-alone therapy is given only to women who have had a hysterectomy, as it can increase the risk of endometrial cancer. Women who still have a uterus are prescribed combined hormone replacement therapy (estrogen plus progestin), which does carry increased risks of breast cancer.

It's also important to note that breast cancer cells are not static.

Like bacteria, these cells "are somewhat of a moving target. They're changing and often reacting to their environment," said Dr. Jennifer Litton, an assistant professor of cancer medicine at the University of Texas MD Anderson Cancer Center in Houston. "It's sort of a mini natural selection. If you expose it to one agent, it will mutate and find a way to resist that agent."

That's why many women become resistant to certain therapies and need alternatives that can outwit these constantly evolving cells.

The authors of the JAMA study concluded that women don't need to be concerned about an increased risk of breast cancer from short-term use of estrogen therapy.

Even so, family history and other risk factors need to be considered before starting a woman on hormone therapy.

But if you have a breast tumor, "estrogen should not be considered for treatment at all," said Jordan. "If they're postmenopausal, those women should either get tamoxifen or an aromatase inhibitor. That is the best treatment that you can give. It's absolutely rock solid."

On an experimental basis, doctors do have the authority to prescribe estrogen to treat women with metastatic breast cancer who have developed resistance to anti-hormone therapies, Jordan added.

More information

The U.S. National Cancer Institute has more on treatments for breast cancer.

Posted: April 2011


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