New Drug Shows Promise Against Advanced Breast Cancer 

Exemestane Holds Off Recurrence Longer Than Tamoxifen 

The first head-to-head comparison of the drugs tamoxifen and exemestane in women with advanced breast cancer shows the latter was not only safe, it also improves disease-free survival.

Exemestane, one of a class of drugs called aromatase inhibitors, is currently approved for women whose cancer progressed while they were taking tamoxifen. Two other aromatase inhibitors are also approved in the US - letrozole and anastrazole.

"We're probably moving into a transition phase where we will be using these types of drugs over tamoxifen in the near future," says Dr. Jay Brooks, chief of hematology/oncology at the Ochsner Clinic Foundation in New Orleans.

Studies Show Exemestane Success

This latest study comes just days after another clinical trial showed the superiority of taking tamoxifen and exemestane sequentially for five years, as opposed to taking tamoxifen alone for the full five years.

The results of these and other studies mark a step forward in the evolution of breast cancer treatment, experts say.

"[Exemestane] will be a good choice for metastatic disease," says Dr. Robert Paridaens, lead author of the study who presented his findings at the Fourth European Breast Cancer Conference in Hamburg, Germany.

"If someone asks me is there a subgroup where it's absolutely a must to start with exemestane, I would say the high-risk patients who are estrogen-receptor-positive who already have a metastasis," he says.

For postmenopausal women with estrogen-receptor-positive breast cancer, the gold standard has been to take tamoxifen for five years after initial treatment for the tumor.

Tamoxifen, which has been available for 20 years, works by interfering with the ability of estrogen to fuel tumor growth.

While many women do benefit from tamoxifen, others fail to respond and, in general, the drug seems to lose its effectiveness after about five years, experts say.

Tamoxifen and exemestane both block the growth of breast tumors that respond to estrogen, but the two drugs work in different ways. Tamoxifen interferes with the ability of breast cancer cells to use estrogen for growth, whereas exemestane interferes with the body's ability to make estrogen.

Aromatase inhibitors may be poised to take the place of tamoxifen. As their name implies, these compounds inhibit aromatase, an enzyme that helps make estrogen. Exemestane is actually slightly different from the other two medications in that it has a "steroidal structure."

One interesting finding in the study, according to Dr. Paridaens, is that there is no adverse affect on patients' lipid profiles, compared to what has been found in studies of non-steroidal aromatase inhibitors.

The new study, sponsored by drug maker Pfizer, involved 382 patients from 81 medical centers in 25 countries. The women were randomly selected to receive either tamoxifen or exemestane, but the study was an "open label" one, meaning both physicians and patients knew who was taking which drug.

The researchers wanted to see if exemestane would increase progression-free survival by three months over tamoxifen. In fact, the results were slightly better than that.

Women in the exemestane group had a median progression-free survival of 10.9 months compared with 6.7 months for those in the tamoxifen group.

Exemestane also led in other categories. Among the women receiving exemestane, 7.4 percent responded completely to the treatment, versus 2.6 percent of the tamoxifen patients. Also, 36.8 percent of the exemestane participants responded partially to treatment, compared to 26.6 percent in the tamoxifen group.

Physicians Look at Best Use for Patients

Although a number of questions still need to be answered, including how long a woman should take exemestane, the drug does seem poised to take its place alongside tamoxifen, even perhaps instead of it, experts say.

How quickly this happens will depend, in part, on whether insurers are willing to reimburse patients for the drug. Exemestane is more expensive than tamoxifen, experts say.

"The question of the future would be does tamoxifen have any role to play in an adjuvant setting? We don't know," Dr. Paridaens says. In any event, the spectrum of medications for breast cancer survivors is expanding. "The number of drugs we have at our disposal is increasing. It's fantastic," he adds.

Always consult your physician for more information.

Online Resources

American Cancer Society

American Society for Clinical Oncology

Centers for Disease Control and Prevention (CDC)

National Cancer Institute

National Cancer Institute Exemestane Study

National Institutes of Health (NIH)

National Women's Health Information Center 

May 2004

New Drug Shows Promise Against Advanced Breast Cancer

Studies Show Exemestane Success

Physicians Look at Best Use for Patients

Blocking Hormone Effects

Preventing Hormone Production

Online Resources

Other Resources:

St. John's Mercy Cancer Services

Find a St. John's Mercy Physician

Breast Health Information

Women's Health Information

St. John's Mercy Classes and Programs

Blocking Hormone Effects

Hormone therapy is used to prevent the growth, spread, and recurrence of breast cancer. The female hormone estrogen can increase the growth of breast cancer cells in some women.

Hormones are chemicals produced by glands, such as the ovaries and testicles. Hormones help some types of cancer cells to grow, such as breast cancer and prostate cancer. Hormone therapy may be considered for women whose breast cancers test positive for estrogen or progesterone receptors.

A hormone receptor test measures the amount of certain proteins (called hormone receptors) in cancer tissue.

Hormones (such as estrogen and progesterone that naturally occur in the body) can attach to these proteins. If the test is positive, it indicates that the hormone is probably helping the cancer cells to grow.

In this case, hormone therapy may be given to block the way the hormone works and help keep the hormone away from the cancer cells (hormone receptors).

If the test is negative, the hormone does not affect the growth of the cancer cells, and other effective cancer treatments may be given.

An antiestrogen drug frequently used, called tamoxifen (Nolvadex®), blocks the effects of estrogen on the growth of malignant cells in breast tissue.

However, tamoxifen does not stop the production of estrogen. Side effects that may occur when taking tamoxifen include hot flashes, nausea or vomiting, vaginal spotting, fatigue, headaches, and skin rash.

Taking tamoxifen also increases the risk of endometrial cancer (involves the lining of the uterus) and uterine sarcoma (involves muscles of the uterus), both cancers of the uterus. There is also a small risk of blood clots and stroke.

A second antiestrogen drug under study for breast cancer prevention, called Raloxifene®, is not recommended for women who have already been diagnosed with breast cancer.

Preventing Hormone Production

Drugs recently approved by the US Food and Drug Administration (FDA), called aromatase inhibitors, are used to prevent the recurrence of breast cancer in postmenopausal women.

These drugs, such as anastrozole (Arimidex®) and letrozole (Femara®), prevent estrogen production.

Anastrozole is effective only in women who have not had previous hormonal treatment for breast cancer.

Letrozole is effective in women who have previously been treated with tamoxifen. Possible side effects of these drugs include osteoporosis or bone fractures.

Another new drug for recurrent breast cancer is fulvestrant (Faslodex®).

Also approved by the FDA, this drug eliminates the estrogen receptor. This drug is used following previous antiestrogen therapy. Side effects for fulvestrant include hot flashes, mild nausea, and fatigue.

Another means of stopping the production of estrogen is the use of surgery to remove the ovaries in women who have not gone through menopause, called an oophorectomy.

Always consult your physician for more information.