Update: Ovarian suppression may reduce breast cancer recurrence

Relevance: Medium-High

Research Timeline: Post Approval

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What is this review about?

This review focuses on ovarian suppression, a treatment for premenopausal women with early breast cancer. Discussion on who may benefit from these treatments is also included, based on a talk by Dr. Prudence Francis of the University of Melbourne at the 2024 San Antonio Breast Cancer Symposium.

Why is this topic important?

Ovarian suppression is a treatment that blocks ovaries from making the hormone estrogen. It is used to improve cancer treatment by reducing the chance of cancer returning (cancer recurrence). It can also help prevent premature menopause and associated impacts and may help preserve ovarian function for later pregnancies.

While estrogen does not cause breast cancer, it may cause cancer to grow and spread. Ovarian suppression is typically combined with hormone therapies (like tamoxifen or aromatase inhibitors) to treat premenopausal women. Studies have shown that combining ovarian suppression with hormone therapy is more effective in reducing cancer recurrence than hormone therapy alone.

Doctors use one of three approaches for ovarian suppression: surgery, radiation or drug injections (a series of shots). Both surgery and radiation permanently stop the ovaries from making estrogen. Ovarian suppression drugs are often given as injections. These injections can pause ovarian function instead of stopping it permanently and are often used in breast cancer. For many people, ovarian function returns after ovarian suppression drugs are stopped. When used before chemotherapy, ovarian suppression may reduce premature menopause and may also help preserve ovary function for those considering pregnancy after cancer treatment.

Ovarian suppression drugs

The FDA has approved three ovarian suppression drugs for use in breast cancer treatment:

• goserelin (Zoladex)
• leuprolide (Lupron)
• triptorelin (Decapeptyl)  

Goserlin (Zoladex) and leuprolide (Lupron) are used more often for breast cancer treatment than triptorelin (Decapeptyl). These drugs, called GnRH agonists, are given as a shot in a doctor’s office every four weeks to pause ovarian function. The ovaries start producing estrogen again after the treatment ends.

A long-acting version of goserlin can be given every three months. This is approved for use in some countries, including the U.S., and was added in 2024 to a major cancer care guideline by the National Comprehensive Cancer Network (NCCN). More data is available about goserlin plus tamoxifen than with aromatase inhibitors, but research is ongoing.

Two other drugs are being evaluated for ovarian suppression: elagolix to treat endometriosis and degarelix to treat prostate cancer. These promising drugs are not yet approved for breast cancer treatment but have potentially useful features: elagolix can be taken as a pill and degarelix may be faster and more reliable than current options.

Who might benefit from ovarian suppression?

Ovarian suppression may help premenopausal people with early-stage breast cancer. It may benefit people who have:

1. Estrogen receptor (ER)-positive breast cancer and meet any of these conditions:
   • are at high risk for recurrence
   • are young (45 and under)
   • plan to take aromatase inhibitor drugs (AIs), including women whose menstrual periods stopped due to chemotherapy (some women's periods resume with AI treatment)
   • have certain types of ER-positive, HER2-negative breast cancer (they may be a candidate for hormone treatment as an alternative to chemotherapy)
2. ER-negative breast cancer, will have to undergo chemotherapy and are done having children
3. Either ER-positive or ER-negative early-stage breast cancer and:
   • will be treated with ribociclib, or
   • will undergo chemotherapy and still want to become pregnant in the future

Important considerations

The following factors are important when considering ovarian suppression:

• Testing effectiveness: Doctors often do not test estrogen levels to assess the effectiveness of these drugs, so it is important to report bleeding or spotting. These symptoms could indicate incomplete ovarian suppression and a need to test estrogen levels.
• Treatment duration: These drugs are typically prescribed for 2-5 years, depending on the person's age, diagnosis and treatment plan.
• Side effects: Ovarian suppression drugs can cause side effects similar to menopause. This can include fatigue, hot flashes, mood changes, vaginal dryness, weight gain and a lack of sexual interest.
• Continuing with treatment: While some people discontinue ovarian suppression because of the side effects or the scheduling of injections, better outcomes are seen for women who continue ovarian suppression throughout their treatment.
• Age: Women under 45 may benefit from these drugs more than older premenopausal women.
• Impact on people with high BMI: Studies indicated that ovarian suppression plus aromatase inhibitors did not work as well for people with a high body mass index (BMI) or for those who had not had chemotherapy. This may be because the drugs did not lower their estrogen levels sufficiently.
• Pregnancy: Some women may still get pregnant after or during pauses in ovarian suppression. Discuss contraception during treatment with your doctor.

What does this mean for me?

If you are premenopausal and have early-stage breast cancer, ovarian suppression drugs could be an option if you are treated with hormone therapy. Aromatase inhibitors—some of the most effective hormone therapies—must be taken with ovarian suppression. Even if your periods have stopped due to chemotherapy, you may still be a candidate for these drugs.

Although it is a useful treatment, ovarian suppression is not for everyone. For example, older premenopausal women with low-risk breast cancers often do very well on tamoxifen alone without ovarian suppression.

Currently, most people in the U.S. who receive ovarian suppression treatment go to a doctor’s office every four weeks for an injection. In 2024, goserelin was added to breast cancer care guidelines as an option that can be given once every three months. Your doctor can help determine if it might be an ideal option for you.

Some people find it hard to stay on these drugs due to the injection schedule or the side effects. However, people who stick with the drug therapy have better outcomes than those who do not. If you experience side effects, consider discussing options for managing them with your doctor.

If you are interested in becoming pregnant in the future, tell your doctor before starting cancer treatment.  Starting ovarian suppression before chemotherapy can improve the chances of preserving your fertility. An oncology fertility specialist can help you explore your options.

Reference

Francis P. Ovarian suppression: Who, when, why, and for how long. Presented at the 2024 San Antonio Breast Cancer Symposium.

Disclosure: FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.

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posted 3/6/25