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SERMs and SERDS for Breast Cancer

Medically Reviewed by Sabrina Felson, MD on March 15, 2022

Selective estrogen receptor modulators (SERMs) and selective estrogen receptor downregulators (SERDs) are types of antiestrogen therapy for breast cancer. These medicines block estrogen, the hormone that certain types of breast cancers use to grow.

Some SERMs also prevent breast cancer in people who are at higher than average risk. These drugs can also prevent and treat the bone-thinning disease, osteoporosis.

Here are a few things to know about SERMs or SERDs if your doctor recommends one of these treatments.

What Are SERMs and How Do They Work?

SERMs are a type of antiestrogen therapy used to treat estrogen receptor-positive breast cancers. These cancers have a protein on their surface called an estrogen receptor. About 75% of all breast cancers are hormone receptor-positive.

When the hormone estrogen attaches to the receptor, it sends signals that tell the cell to grow. SERMs block estrogen receptors in the breast so that estrogen can't attach to the cancer cells and help them multiply. These medicines are called "selective" because they block the action of estrogen in breast cells, but can turn that action on in others. Many other types of cells also have estrogen receptors, including cells of the bones and uterus.

It's important to know that SERMs aren't the same as hormone replacement therapy (HRT) some women take to treat menopause symptoms like hot flashes and mood swings. HRT contains the hormones estrogen and progesterone. Antiestrogen therapy for breast cancer blocks these estrogen hormones.

Three SERMs have been approved to prevent or treat breast cancer:

Tamoxifen (Nolvadex, Soltamox) is mainly used in women who haven't gone through menopause. It can also be used for women who’ve gone through menopause and in men with breast cancer. This medication:

  • Treats late-stage breast cancer
  • Treats early-stage breast cancer after surgery
  • Reduces the risk of cancer coming back after surgery for ductal carcinoma in situ (DCIS)
  • Lowers the chance of getting breast cancer in people who are at higher than average risk

Toremifene (Fareston) treats late-stage breast cancer in postmenopausal women. It doesn't work as well in people who have already taken tamoxifen, but it has stopped working.

Raloxifene (Evista) isn't a breast cancer treatment. It's mainly used to treat bone loss in postmenopausal women. But Evista can also reduce the risk of breast cancer in postmenopausal women with osteoporosis.

What Are SERDs and How Do They Work?

Like SERMs, SERDs (sometimes called ERDs) are a type of antiestrogen therapy. SERDs fill estrogen receptors to stop this hormone from attaching to cancer cells and helping them grow. These medicines also reduce the number of estrogen receptors and change the receptors that remain so they don't work as well.

Fulvestrant (Faslodex) is the only approved SERD. Faslodex treats late-stage, hormone receptor-positive breast cancers that are also HER2-negative. This means the cancer cells don't have any or much of a protein called HER2 on their surface. HER2 helps to control cell growth.

This medication is:

  • A first treatment for late-stage hormone receptor-positive, HER2-negative breast cancer in postmenopausal women
  • A treatment for postmenopausal women with late-stage HER-positive breast cancer who have already taken a different hormone therapy
  • Combined with ribociclib (Kisqali) to treat late-stage hormone receptor-positive, HER 2-negative breast cancer in postmenopausal women
  • Combined with palbociclib (Ibrance) or abemaciclib (Verzenio) to treat late-stage hormone receptor-positive, HER 2-negative breast cancer in women whose cancer grew after they took a different hormone therapy

How Do You Take Them?

All of the SERMs come as a pill, except Soltamox, which is a liquid. Depending on which of these medicines you take, the doses range from 20 milligrams (mg) to 60 mg a day.

If you take a SERM to lower your risk for breast cancer, you'll usually stay on the medicine for 5 to 10 years.

Faslodex, a SERD, comes as two shots. You get one shot into each buttock. Each injection takes 1 to 2 minutes. You'll get this treatment three times in the first month, and then once a month after that.

What Types of Breast Cancer Do They Treat?

SERMs treat estrogen receptor-positive breast cancers. About two out of every three breast cancers are this type. These cancers grow when they're exposed to the hormone estrogen.

The SERD Faslodex treats late-stage hormone receptor-positive, HER2-negative breast cancers. It's sometimes combined with other cancer medications.

When Are SERMS Given as Breast Cancer Treatment?

There are a few situations when your doctor might prescribe an SERM.

Before surgery. If your cancer is large, an SERM can shrink the tumor and make it easier to remove. Another name for treatments before surgery is neoadjuvant therapy.

After surgery. Sometimes a few stray cancer cells can be left behind after surgery. Taking SERMs helps to prevent the cancer from growing again or coming back. The name for this type of treatment is adjuvant therapy.

For late-stage cancer. Hormone therapy can slow cancer that has spread outside of your breast to other parts of your body.

To prevent breast cancer. If you haven't had breast cancer but you are at higher than average risk for it, taking a SERM could protect you from getting this cancer in the future.

When Are SERDS Given as Breast Cancer Treatment?

There are a few situations when your doctor might prescribe a SERD.

As a first treatment. A SERD can help slow a cancer that has spread to other parts of your body.

After hormone therapy. You might get this treatment if your cancer kept growing after you took hormone therapy.

With another medication. A SERD can be added to other medications as a first treatment, or after you've taken a different hormone therapy and your cancer has spread.

How Effective Are SERMS and SERDs for Breast Cancer Treatment?

Taking a SERM if you're at risk for a hormone-positive breast cancer could lower your chance of getting breast cancer by about 40%. Using tamoxifen after surgery might lower the risk of your cancer coming back, and possibly help you live longer. If you have a late-stage cancer that has spread to other organs, this medication might slow the tumor or even stop it.

Although SERMs can reduce the risk for cancer, they do have side effects, some of which can be serious. Your doctor will weigh your cancer risk against concerns about side effects before recommending this treatment for you.

The effectiveness of Fulvestrant depends on your stage of cancer, when you take it, and whether you combine it with another cancer drug. Studies show that this medication can improve both overall survival and progression-free survival, which is the length of time that passes without your cancer growing. The sooner after your diagnosis you get this treatment, the better your outcome.

What Are the Risks and Side Effects of SERMS for Breast Cancer?

The most common side effects from the SERMs are similar to menopause symptoms, including:

Some women have a tumor flare when they first start taking tamoxifen. Their tumor grows larger and causes bone pain. This side effect usually goes away quickly.

Rarely, SERMs cause more serious side effects like these:

These medicines could be risky to take if you:

If your doctor recommends SERMs to prevent or treat breast cancer, have a conversation about how these medicines might help you. Ask about the possible side effects, and how long you will need to stay on the treatment. And find out what other treatments are available to you.

What Are the Risks and Side Effects of SERDS for Breast Cancer?

The most common side effects from Fulvestrant are:

  • Temporary pain at the injection site
  • Nausea
  • Bone, muscle, or joint pain
  • Headache
  • Tiredness
  • Hot flashes

This medicine can reduce the number of platelets, cells that help your blood clot. It may increase your risk of bleeding.

Fulvestrant can harm a growing baby. Avoid this medication if you are pregnant, trying to get pregnant, or breastfeeding. Use a nonhormonal form of birth control while you take this medicine, and for at least one year after you finish your last dose.

Show Sources

SOURCES:

American Cancer Society: "Hormone Therapy for Breast Cancer," "Tamoxifen and Raloxifene for Lowering Breast Cancer Risk."

BreastCancer.Org: "Faslodex," "Hormonal Therapy."

Breast Care: "Real-World efficacy of Fulvestrant Monotherapy as the First Treatment or Maintenance Treatment in Patients with Metastatic Breast Cancer."

Eli Lilly: "Evista."

FDA: "Nolvadex," "Soltamox," “Fareston,” "Faslodex."

National Cancer Institute: "Estrogen Receptor," "HER 2-Negative."

Pharmacology & Therapeutics: "Selective estrogen receptor modulators (SERMs) and selective estrogen receptor degraders (SERDs) in cancer treatment."

The Breast Journal: "Real-world effectiveness of fulvestrant monotherapy as first endocrine treatment in patients with metastatic breast cancer."

UpToDate: "Medications for the Prevention of Breast Cancer."

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