Comparing Hormonal Therapies

You and your doctor will need to discuss the various types of hormonal therapy and compare them in order to decide which one is right for you.

There are four different types of hormonal therapy. They either slow down or stop estrogen's ability to turn on the growth of hormone-receptor-positive breast cancer cells. Learn more about research developments in hormonal therapy.

• Tamoxifen—the best-known selective estrogen-receptor modulator (SERM)—takes the place of estrogen inside the estrogen receptors. Tamoxifen is approved for pre- and post-menopausal women, for all stages of hormone-receptor-positive disease, before and after surgery.
• Aromatase inhibitors lower estrogen production after menopause. Aromatase inhibitors are only for post-menopausal women with hormone-receptor-positive disease. All three (Arimidex [chemical name: anastrozole], Aromasin [chemical name: exemestane], and Femara [chemical name: letrozole]) are approved for women with advanced (metastatic) disease. Each aromatase inhibitor is also approved for women with early-stage disease at different times after surgery.
• Faslodex—the only estrogen-receptor downregulator (ERD)—eliminates the hormone receptors. Faslodex is a treatment for post-menopausal women with hormone-receptor-positive metastatic breast cancer. This treatment is an option after other hormonal treatments, such as aromatase inhibitors or tamoxifen, have stopped working. Faslodex may also be combined with another form of hormonal therapy.
• Ovarian shutdown and removal lower estrogen production in pre-menopausal women with hormone-receptor-positive breast cancer. Ovarian shutdown is a medical treatment that stops the production of estrogen in the ovaries. Ovarian removal is a surgical procedure.

As you and your doctor begin to think about the right hormonal treatment for YOU, you will want to compare drugs within their own categories and compare treatments across categories. Certain drugs have been tested together, so comparisons are based on the results of hundreds and sometimes thousands of women in clinical trials. Other drugs have not been tested against one another, so they can't be directly compared.

Depending on your personal situation, you may make one choice now, and switch to another as your medical needs change.

Differences between SERMs

Tamoxifen is the most commonly used hormonal therapy around the world and is also the most commonly used SERM. Tamoxifen represents the standard of care for pre-menopausal women with hormone-receptor-positive breast cancer with any stage of disease. It can also be used for post-menopausal women who have hormone-receptor-positive breast cancer.

Toremifene (brand name: Fareston) is approved only for post-menopausal women with metastatic disease. This drug may be associated with a slightly lower risk of endometrial cancer than tamoxifen. However, toremifene has not been around as long as tamoxifen, and it has only been tested for women with advanced disease. It is not prescribed nearly as often as tamoxifen. That's because doctors are more familiar with tamoxifen and with the studies that show tamoxifen's benefits for both early-stage and advanced cancer.

Differences among aromatase inhibitors

Each aromatase inhibitor (Arimidex, Aromasin, and Femara) worked better than tamoxifen whenever they were compared in clinical trials. But we don't know exactly how any one aromatase inhibitor compares to the other two because no clinical trials have directly compared them.

When studies of different aromatase inhibitors are compared, though, the three medicines seem to have very similar benefits and side effects. In post-menopausal women with hormone-receptor-positive disease, all three aromatase inhibitors have been able to:

• lower the risk of breast cancer coming back,
• decrease the risk of developing a new breast cancer in either breast, and
• slow or stop progression of advanced disease.

Each aromatase inhibitor is approved by the FDA for early-stage disease at different times after surgery:

• Arimidex—immediately after surgery.
• Aromasin—after two to three years of tamoxifen.
• Femara—immediately after surgery and after five years of tamoxifen.

All three aromatase inhibitors are approved by the U.S. Food and Drug Administration (FDA) for women with advanced hormone-receptor-positive breast cancer. And for these women, most doctors think that the three medicines do the same things and do them equally well. Some doctors think that choosing one to treat advanced disease is almost like deciding between Coke and Pepsi.

The aromatase inhibitors do have some slight differences in side effects so you might find one of the three drugs easier to tolerate. Sometimes your doctor may just be most familiar with one of the drugs and therefore may prescribe it more often.

Differences between SERMs and aromatase inhibitors

Since aromatase inhibitors are effective only in post-menopausal women with hormone-receptor-positive breast cancer, aromatase inhibitors and SERMs can only be compared in women who are beyond menopause.

Before 2004, all post-menopausal women were given tamoxifen as the first hormonal treatment after surgery (adjuvant treatment). However, new studies showed that aromatase inhibitors gave better results than tamoxifen. New guidelines were set, based on these studies, and the standard of care then changed for post-menopausal women with hormone-receptor-positive breast cancer. For this reason, many physicians now:

• start out with Arimidex, or Femara, or
• switch women to Arimidex or Aromasin after two to three years of tamoxifen, or
• switch women to Femara after completing five years of tamoxifen.
• Your doctor may also switch you to an aromatase inhibitor if tamoxifen is no longer working against the breast cancer, or if you find the side effects of tamoxifen difficult to manage.

Differences among SERMs, aromatase inhibitors, and ERDs

Faslodex (chemical name: fulvestrant) is the only estrogen-receptor downregulator currently approved by the FDA to treat post-menopausal women with advanced hormone-receptor-positive breast cancer that's stopped responding to hormonal therapy such as tamoxifen or aromatase inhibitors.

The decision to use tamoxifen, aromatase inhibitors, or Faslodex depends on a woman's individual situation. Here are three possibilities:

• If you were pre-menopausal, have taken two to five years of tamoxifen, but the cancer has come back and you are now post-menopausal, your doctor might suggest an aromatase inhibitor next.
• If you are post-menopausal, took an aromatase inhibitor for two to five years, but the cancer has come back, your doctor might switch you to another aromatase inhibitor.
• If you are post-menopausal, have advanced disease, and have already tried several aromatase inhibitors, your doctor might switch you to Faslodex or back to tamoxifen.

Differences between ovarian shutdown and ovarian removal

Ovarian shutdown and removal are only for pre-menopausal women with hormone-receptor-positive breast cancer.

Ovarian shutdown uses medication to stop the ovaries from producing estrogen. You are given an injection (shot) of a small implant under the skin of your belly. You will get one of these injections every four weeks for several months. Your doctor will give you blood tests to see how your estrogen levels have dropped over time.

Ovarian removal is a surgical procedure. You will have two small incisions (cuts) in your belly area, and the ovaries will be removed through those incisions. Although this is an operation, it is not major surgery, and you will probably be up and about within a couple of days.

Both methods dramatically reduce the amount of estrogen in the body. Since either method basically puts you into menopause, you may begin to have symptoms such as hot flashes, vaginal dryness, weight gain, and fatigue. However, surgery puts you into menopause as soon as you have the operation, whereas taking medicine every month gives your body more time to adjust to lower estrogen levels.

Both methods also cause infertility, so that you cannot have children in the future. However, there are other options, such as surrogate parenting and adoption.

The strategy that's right for YOU

Hormonal therapies can be used in many different situations. And treatment recommendations can change over time based on your needs, the benefits you're getting, how you're dealing with therapy, and new medical advances. Each time you see your doctor in follow-up, it's important to review, confirm, or change your hormonal treatment based on the strategy that's right for YOU.