Selective estrogen receptor degraders (SERDs) are drugs that treat breast cancer. Clinical trials suggest SERDs taken by mouth may be more effective than first-generation injectable SERDs for people with endocrine therapy resistance.
Breast cancer can be hormone receptor-positive or hormone receptor-negative. This means the cancer cells either bind to or do not bind to the hormones estrogen or progesterone.
Estrogen receptor-positive (ER-positive) cancer cells need estrogen to grow. SERDs are a type of endocrine therapy that work to lower estrogen levels in your blood or inhibit estrogen receptors, which can delay or stop cancerous growth.
Although endocrine therapy works for many people, some cancers may become resistant to treatment. SERD drugs are often effective for cancers that are resistant to other types of endocrine therapy.
This article will discuss what SERD drugs do, the difference between oral and injectable forms, and common side effects.
What are oral SERDs?
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Oral SERDs are drugs you take by mouth to treat a specific type of breast cancer that needs estrogen to grow. SERDs also come in injectable form.
Breast cancer cells can have protein receptors that bind with estrogen or progesterone, or both. In other words, these cancer cells need these hormones to survive. About 3 in 4 cases of breast cancer has at least one type of hormone receptor.
Some forms of endocrine therapy for people with ER-positive cancer focus on lowering estrogen levels. This may be done instead of or in addition to chemotherapy.
Estrogen-lowering medications work in two different ways. They can either interfere with the estrogen binding process, or they can induce estrogen breakdown, also called degradation.
SERDs belong to the group of medications that work on estrogen breakdown. This degradation slows or prevents the growth of ER-positive breast cancer cells.
Up until recently, the Food and Drug Administration (FDA) had approved only one SERD therapy called fulvestrant (Faslodex), which comes in the form of intramuscular injection.
In January 2023, the FDA approved an oral SERD called elacestrant (Orserdu). In clinical trials, elacestrant resulted in higher survival rates compared to fulvestrant.
Other oral SERDs are currently in clinical trials or under development pending FDA approval.
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Oral SERD drugs may have greater bioavailability than injectable SERDs, making them a potentially better option for some people with breast cancer. A higher bioavailability means the body has an easier time absorbing and using the drug.
A few endocrine therapies exist for ER-positive breast cancer. They include:
luteinizing hormone-releasing hormone (LHRH) agonists such as goserelin and leuprolide
selective estrogen receptor modulators (SERMs) such as tamoxifen
selective estrogen receptor degraders (SERDs), such as fulvestrant
Although endocrine therapy is an effective early treatment for ER-positive breast cancer, many cases develop resistance. As a result, the drugs stop working.
Oral SERDs can work in cases where resistance to other endocrine therapies has developed.
In about 50% of cases of endocrine therapy resistance in metastatic breast cancer, a difference in the ESR1 gene seems to be the underlying cause.
Cancers with the ESR1 difference become resistant most often to aromatase inhibitors but not to SERMs (tamoxifen) or SERDs (fulvestrant).
Fulvestrant works on cancerous tumors even when there is an ESR1 gene difference. For people whose endocrine therapy resistance is associated with the ESR1 gene, fulvestrant can remain an effective cancer treatment.
The greater bioavailability of oral SERDs allows the drug to act potently, including in cases where treatment resistance was developed.
Examples of oral SERD drugs
A few oral SERD medications are in development, but only elacestrant (Orserdu) is approved by the FDA.
Elacestrant (Orserdu)
In an earlier clinical trial, people who received elacestrant experienced longer progression-free survival rates than those who received fulvestrant. The chance of cancer progression or death was 32% lower among all people who took the oral SERD and 50% lower for those with the ESR1 gene difference.
Other oral SERDs
Researchers are actively looking at bringing new oral SERDs to the market.
Doctors prescribe elacestrant after trying at least one endocrine therapy.
How are oral SERDs taken?
The oral SERD drug is for adult men and postmenopausal women whose breast cancer has the following features:
ER-positive
HER2-negative
ESR1 mutated advanced or metastatic breast cancer
HER2 negative means the breast cancer does not have higher levels of a protein called HER2.
Dosing and administration of oral SERDs
Elacetrant comes as a pill you take with food. The usual dose is 345 mg once per day.
Your medical professional might not prescribe elacetrant or might recommend a lower dose if you have liver failure, impairment, or experience an adverse reaction.
SERDs are not recommended for people who are nursing.
In clinical trials for elacetrant, some people experienced increased levels of cholesterol or triglycerides. Data also showed higher creatinine and lower sodium levels.
Summary
Oral SERDs are medications you take by mouth to treat a type of breast cancer that is associated with estrogen.
First-generation injectable SERDs offered new treatment options for people with endocrine therapy-resistant breast cancer. However, they have suggested limited bioavailability.
Oral SERDs are more potent and may have greater effectiveness. Elacestrant is the only oral SERD currently approved by the FDA, but several more are in trials or under development.
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Article resources
Bidard F-C, et al. (2022). Elacestrant (oral selective estrogen receptor degrader) versus standard endocrine therapy for estrogen receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer: Results from the randomized phase III EMERALD trial. https://ascopubs.org/doi/full/10.1200/JCO.22.00338
