"New breast cancer drug holds long-term promise"

[Guest Ian Wong]

Here's a pretty big article that was published in the NEJM today regarding the role of anti-estrogen drugs in the treatment of breast cancer. To date, tamoxifen has been the drug of choice for treatment of estrogen receptor positive breast cancer. This may change in the future, and this NEJM article states that in a very selected group of patients, that aromatase inhibitors may be superior to tamoxifen in reducing breast cancer recurrence.

 

As a quick summary, breast cancer cells may have estrogen receptors on them (ER+) or may lack estrogen recepters (ER-). For those breast cancers which are tested and found to be receptor-positive, blocking those receptors has been found to inhibit their growth. Tamoxifen's mechanism of action isn't fully known, but it is believed to bind to those estrogen receptors on cancer cells and prevent estrogen hormones from binding on those receptors. You could call tamoxifen an estrogen receptor antagonist (inhibits estrogen from binding).

 

This new class of drugs that has been tested works on a different mechanism. These drugs inhibit aromatase, which is an enzyme that converts other steroid molecules into estrogen. As a result, these drugs help block your body's production of estrogen. This lowers the amount of estrogen in your body that is available to stimulate the growth of any remaining breast cancer cells. There are three such aromatase inhibitors on the market: anastrazole (Arimidex), exemestane (Aromasin), and letrozole (Femara).

 

Ian

 

Here's the link to the NEJM website, and the abstract that is available for free online:

 

A Randomized Trial of Exemestane after Two to Three Years of Tamoxifen Therapy in Postmenopausal Women with Primary Breast Cancer. NEJM. March 11, 2004. Volume 350:1081-1092.

content.nejm.org/cgi/content/short/350/11/1081

 

www.canada.com/national/nationalpost/news/story.html?id=6e3a9396-276e-4db5-8944-c8807e6e769a

 

New breast cancer drug holds long-term promise

Aromasin cuts estrogen production, researchers say

 

Brad Evenson

National Post

March 11, 2004

 

The drug tamoxifen, once the gold standard of breast cancer treatment, is being surpassed by a new drug that cuts estrogen production.

 

In a large, international study of women who got breast cancer after menopause, patients with early stage cancer who switched after two years from tamoxifen to Aromasin were significantly more likely to be cancer-free after five years.

 

"This trial, I think, puts the death nail into tamoxifen being a five-year treatment," said Paul Goss, director of breast cancer prevention at Princess Margaret Hospital in Toronto.

 

"It's inconceivable to me that a patient would want to continue five years of tamoxifen and not switch over to this drug during that five years."

 

The clinical trial, published today in the New England Journal of Medicine, applies to the 70% of women whose breast cancers are fuelled by estrogen. It does not apply to women who have not gone through menopause or have non-estrogen driven tumours.

 

Experts predict these findings will have a major impact on the treatment of the 21,200 women diagnosed with breast cancer each year in Canada.

 

Until now, tamoxifen was regarded as the best long-term drug strategy for women whose breast cancer was caught early and removed.

 

The drug binds to tumour cell sites and prevents estrogen from connecting to such cells and triggering cancer.

 

The problem is that cancer cells grow resistant to tamoxifen, so some women suffer recurrences. The drug also raises the risk of uterine cancer and stroke.

 

A new class of drugs known as aromatase inhibitors, including Aromasin, Femara and Arimidex, works by lowering the production of estrogen itself.

 

Recent studies have looked at shifting women from tamoxifen to the newer drugs. But longer-term studies are now looking at the possibility of replacing the older drug from the first day of treatment.

 

"I would say tamoxifen is slowly being buried," Dr. Goss says.

 

In the current study, which involved 4,742 women from around the world, 91.5% of women who switched to Aromasin were free of breast cancer after five years, compared with 86.8% of the women who took tamoxifen for the full five years.

 

Of the 54 women who suffered a recurrence of disease in their breast, 33 were in the tamoxifen group while 21 took Aromasin -- one third less. Of the 288 women whose cancer spread to other parts of the body, 114 took Aromasin while 174 took tamoxifen. Among the 29 women who developed cancer in their other breast, nine were taking Aromasin and 20 were taking tamoxifen.

 

The results were the same regardless of whether women had chemotherapy and radiation for their cancer or not.

 

Experts say cancer doctors are likely to start patients on Aromasin after two years of tamoxifen, then switch them at five years to Femara, another estrogen reducing drug. A recent study showed the drug has big advantages over tamoxifen in long-term prevention.

 

"I think with these two studies together, the strategy of switching from tamoxifen to these aromatase inhibitors will become a new standard," said Jeff Abrams, associate chief of clinical research at the U.S. National Cancer Institute.

 

Researchers say Aromasin, which is taken once a day with meals, has relatively mild side effects. These include hot flashes, fatigue, insomnia, headaches, vaginal dryness, sexual dysfunction, bone thinning, joint pain and diarrhea.

 

The study was partially funded by Pfizer, which makes Aromasin.