Interesting article for ER+ people.
Interesting article for ER+ people. sciencedaily.com/releases/2005/12/051207113139.htm
Some of you may already have heard about this, but it was news to me and encouraging news at that! I know we are lucky to have hormone therapy, but there is always the problem of eventual resistance and this shows a way round it.
Kathy
Kathyf Thanks for posting about the article. Unfortunately although I have typed the link in several times very carefully I can’t get article. I am not ER+ but I know someone who is and I wondered if there is anyway you can summarise the way round the problem of the treatment ceasing to work and post it on the forums for us. I hope it doesn’t involve too much work but it is a very interesting and probably useful article that you have drawn out attention to.
Best wishes
Roisin
— hi Roisin — I hope Kathy doesn’t mind my posting the following. i just got into the site.
Joy x
Researchers Say Estrogen Can Kill Breast Cancer Cells Once Fueled By The Hormone
Fox Chase Cancer Center researchers say some breast cancer cells once fueled by estrogen can be killed by the same hormone. This raises the possibility that estrogen therapy after estrogen deprivation may overcome the cells’ eventual resistance to hormone therapy. The finding by V. Craig Jordan, Ph.D., D. Sc., and his colleagues at Fox Chase is published in the December 7 issue of the Journal of the National Cancer Institute.
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Many breast cancer cells (called estrogen receptor-positive breast cancers) require estrogen for survival. Women with these types of breast cancers are treated with drugs that that block estrogen, such as tamoxifen, fulvestrant, or aromatase inhibitors, causing the cells to die in a process called apoptosis. However, over time, these cancer cells learn to adapt and become resistant to this therapy.
“Tamoxifen and other estrogen inhibition drugs have been remarkably successful in the treatment of hormone-responsive breast cancers,” said Jordan, vice president and scientific director for the medical science division at Fox Chase. “However, cancer cells are smart and they figure out how to survive these treatments. We believe we’ve become savvy to their art. Our laboratory study demonstrates that these same breast cancer cells die when we re-introduce them to estrogen.” Jordan was the leader in the development of the use of tamoxifen to treat breast cancer. He holds the Alfred G. Knudson Jr., M.D., Ph.D., Chair in Cancer Research at Fox Chase.
The mechanism by which estrogen promotes apoptosis is not well understood. To understand this process, Jordan and his colleagues developed a line of breast cancer cells, called MCF-7:5C. These cells already are resistant to estrogen withdrawal. When the researchers treated MCF-7:5C cells with very small concentrations of estradiol they underwent apoptosis. The researchers also tested these cells in mice to see how this process might influence existing tumors. Again, the exposure to estradiol caused the cancer cells to die.
“These laboratory data have important clinical implications, particularly for the use of aromatase inhibitors as long-term therapy,” write the authors, “and they suggest that, if and when resistance to aromatase inhibition occurs, a strategy of treatment with estrogen … may be sufficient to kill the cancer and control disease progression.”
Sorry Roisin I can see now why you’ve had problems. If you view the site on medium text size, which most people do in order to be able to read and post easily, the very end of the link disappears off the end of the page. It should read “htm” not “htr”, which is what it looks like:-)
Thanks for copying and posting the article, Joy. I should have done that myself in the first place.
Below is an American newspaper report on the same findings.
Kathy
It sounds like a paradox, and it is: Even though estrogen can trigger the growth of breast cancer cells, small doses of the hormone can also help kill tumor cells. In fact, low-dose estrogen may help breast cancer patients who’ve become resistant to therapies that work by blocking the hormone. Now, researchers investigating this puzzle say they’ve discovered how estrogen kills these resistant tumor cells.
“It’s all counterintuitive,” says V. Craig Jordan, the Alfred G. Knudson Chair of Cancer Research at the Fox Chase Cancer Center in Philadelphia. Jordan is widely hailed as the “father of tamoxifen” for his efforts in developing the estrogen-blocking drug that helps prevent breast cancer recurrence.
If estrogen is given at a specific time, he says, “instead of stimulating the growth (of breast cancer cells), it sees these dysfunctional aberrant cancer cells, and instead of telling them to grow, tells them to die.” Jordan’s team has published a series of papers in the scientific literature over the last few years showing that this is in fact the case. “Now, we have found out the mechanism,” he says.
Reporting in the Dec. 7 issue of The Journal of the National Cancer Institute, Jordan’s team found that the form of estrogen called estradiol induces cell death, or apoptosis, by activating a specific chemical pathway. This pathway is controlled by proteins on the membrane of the cells called mitochondria.
“We basically blow up the mitochondria with the estrogen,” Jordan says. The “blowing up” stimulates the release of a molecule called cytochrome c within the cell. Cytochrome c, in turn, activates several enzymes that initiate cell death.
The study was conducted using breast cancer cell lines resistant to estrogen withdrawal. These cells underwent cell death when treated with very small concentrations of estradiol. The estrogen was 100 percent effective in killing the cancer cells, Jordan says.
Kill rates were higher in cells treated with estradiol, compared to those treated with fulvestrant, an estrogen-blocker, or cells from an untreated control group. Jordan’s team also injected estrogen-treated cancer cells into mice, resulting in complete tumor regression.
Typically, women with estrogen-receptor positive breast cancers are put on treatments that block estrogen, such as tamoxifen, fulvestrant or aromatase inhibitors. For some reason, women may become resistant to this long-term therapy, with some cells adapting and thriving – even when deprived of estrogen.
“The study gives clinicians reassurance that they might consider estrogen as another alterative therapy for women with advanced breast cancer who have grown resistant to aromatase inhibitors,” says Dr. Christy Russell, associate professor of medicine at the University of Southern California Keck School of Medicine, Los Angeles, and national chair of the breast cancer advisory group of the American Cancer Society.
Jordan says his team hopes to start clinical trials involving low-dose estradiol soon. “This is a true example of things we find in the laboratory that we can apply to patients very quickly,” he says.
Women with breast cancer who have undergone treatment and then are put on the estrogen-blocking therapies often stop responding, Jordan says. About 50,000 women (in the U.S.) a year have this drug-resistance problem," he estimates. “We’d probably be able to help a third of those” with the estrogen treatment, he adds.
It wouldn’t require big doses, Jordan says. He estimates that a dose of about 1.5 milligrams a day, given for eight to 12 weeks, might overcome the resistance and kill the cancer cells. Conventional hormone replacement therapy, when given more widely, typically involves 0.625 milligrams of estrogen daily.
Another expert, Dr. Ann Partridge, a medical oncologist specializing in breast cancer at the Dana-Farber Cancer Institute in Boston, applauds the study. “The news here is, they are figuring out the mechanism," she says. The other good news is that “a physiological dose (what the body would normally make) of estrogen can have an effect.”
Joy and Kathy Many thanks for this information. I will pass it on. Its very interesting isn’t it?
Best wishes
Roisin
— hI Roisin and Kathy — Yes. I was also interested in the link page on phytoestrogens effect on breast cancers as this does concern me as I use a lot of Soy products. But then noticed it was dated 2004. I would love to know the VERY latest research results on this.
Joy x