Hormone receptor-positive metastatic breast cancer

In metastatic breast cancer, the cancer cells have spread beyond the breast and nearby lymph nodes to form tumors in other tissues or organs, in some cases far away from the breast. Metastatic breast cancer can be:

• Hormone receptor-positive, which means the cancer cells have receptors for estrogen (ER+) or progesterone (PR+), or both (ER+/PR+) and these hormones help the cancer to grow
• HER2-positive, which means the cancer cells have too many copies of the HER2 gene and too many HER2 receptors, leading to too many signals to grow and divide
• HER2-low, which means the cancer cells have some HER2 receptors, but not enough to be considered HER2-positive
• HER2-ultralow, an even lower level of HER2 receptors
• Both hormone receptor-positive and HER2-positive
• Both hormone receptor-positive and HER2-low
• Both hormone receptor-positive and HER2-ultralow
• Triple-negative, which means the cancer cells test negative for hormone receptors and HER2 receptors

Metastatic hormone receptor-positive breast cancer is hormone-sensitive and can be treated with hormonal therapy. You can find more information on how metastatic breast cancer is diagnosed on our pages about metastatic breast cancer and testing.

If you had early-stage hormone receptor-positive breast cancer that is now metastatic, your medical oncologist may recommend a biopsy of any abnormal finding from an imaging test.

Examining and testing the biopsy tissue helps doctors:

• Diagnose the cancer
• Confirm the cancer is metastatic
• Confirm the presence or absence of biomarkers such as hormone and HER2 receptors to make sure the status did not change from your original diagnosis
• Confirm other biomarkers, such as proteins or gene mutations, that can help you and your doctor choose treatments that target those biomarkers

Treatments for hormone-receptor positive metastatic breast cancer

Treatment for metastatic breast cancer has two goals. The first is to keep the cancer under control for as long as possible. The second is to maintain your quality of life, or overall enjoyment of life.

Treatments for HR-positive metastatic breast cancer may include:

• Hormonal therapy
• Targeted therapy
• Chemotherapy
• Radiation therapy
• A combination of these treatments

Surgery is rarely done for metastatic breast cancer; there are several reasons your doctor may recommend it. For example, if other treatments keep the cancer from growing for some time, your doctor might recommend removing the primary, or original, breast tumor, and in rare cases, a metastatic lesion from the lung or liver. Another example is if you have pain or bleeding, your surgeon might remove the original breast tumor to help ease your symptoms.

Hormonal therapy

In hormone-sensitive breast cancers, hormonal therapy can work as well as or even better than chemotherapy.

The type of recommended hormonal therapy depends on your menopausal status.

• Premenopausal means that you are still having menstrual periods and you are not having any symptoms of menopause, such as hot flashes.
• Menopausal means that your periods have stopped for 12 months.

Menopause can happen naturally, or it can happen as a result of chemotherapy, temporary ovary suppression with medicine, or surgery that removes the ovaries, called oophorectomy. With oophorectomy, menopause is immediate and permanent.

There are several types of hormonal therapy for metastatic hormone receptor-positive disease, and you may be switched from one to another over time if one medicine stops working against the cancer.

SERMs, or selective estrogen receptor modulators, work against estrogen receptor–positive metastatic breast cancers in pre- and postmenopausal women and in men.

• The most commonly used SERM is tamoxifen.
• Toremifene (Fareston), which is closely related to tamoxifen, is used in postmenopausal women with hormone-sensitive metastatic breast cancer or with an unknown receptor status. Studies show it works as well as tamoxifen and has similar side effects. These medicines are taken as a daily pill.

Aromatase inhibitors may be given as a first treatment for metastatic breast cancer in postmenopausal women, or after tamoxifen or other hormonal treatments stop working. The names of these medicines, which you take as a daily pill, are:

• Anastrozole (Arimidex)
• Letrozole (Femara)
• Exemestane (Aromasin)

Aromatase inhibitors increase the risk for bone thinning and osteoporosis, which can lead to bone breaks. Your doctor will monitor you and may recommend bone-strengthening medicine, if needed.

SERDs, or selective estrogen receptor downregulators, stop activity of estrogen on cancer cells, keeping them from growing. They can also break down or weaken estrogen receptors, making them inactive. SERDs are also known as estrogen receptor antagonists (ERAs). They are approved only for use in metastatic disease. They are used when the cancer no longer responds to other hormonal therapies. The SERDS are:

• Fulvestrant (Faslodex). Fulvestrant is injected into a muscle every 4 weeks. Hot flashes, mild nausea, and fatigue are the major side effects.
• Elacestrant (Orserdu). Elacestrant is a pill taken by mouth every day. This medicine is FDA-approved to treat metastatic breast cancer that has tested positive for an ESR1 mutation. Muscle and joint pain, nausea, fatigue, and high cholesterol are the most common side effects.

LHRH agonists (luteinizing hormone-releasing hormones) suppress ovarian function. They are typically used when premenopausal women receive treatments that require them to be postmenopausal, such as aromatase inhibitors. Two LHRH medicines are approved for use in women who have not yet gone through menopause. Goserelin (Zoladex) and leuprolide (Lupron or Eligard) are both given as a monthly injection.

Targeted therapy

A growing number of targeted therapies are approved to treat hormone-receptor positive metastatic breast cancer. They work in different ways.

AKT inhibitors target the AKT protein, which plays a role in cell communication that can help some breasts cancers to grow. AKT inhibitors stop the AKT protein from working. This interferes with the the cancer’s ability to grow. There is one AKT inhibitor approved to treat breast cancer: Capivasertib (Truqap). This drug is approved for hormone receptor-positive, HER2-negative metastatic breast cancer that tests positive for AKT1, PIK3CA, or PTEN mutations.

CDK 4/6 inhibitors, also called cyclin-dependent kinase 4/6 inhibitors, target two specific kinases, or enzymes, called kinase 4 and kinase 6. This type of medicine slows the growth or spread of cancer cells. Three CDK 4/6 inhibitors are approved to treat hormone receptor-positive, HER2-negative metastatic breast cancer:

• Abemaciclib (Verzenio)
• Palbociclib (Ibrance)
• Ribociclib (Kisqali)

CDK 4/6 inhibitors are pills. Possible side effects include stomach problems, diarrhea, infection, low blood counts, headache, hair loss, fatigue, and decreased appetite.

mTOR inhibitors work to slow or stop the protein mTOR’s role in the growth of cancer cells. Everolimus (Afinitor) is the mTOR inhibitor that is FDA approved to treat hormone receptor-positive, HER2-negative metastatic breast cancer. Everolimus is taken as a daily pill. Common side effects include cough, diarrhea, infection, mouth sores, and weakness.

PI3K inhibitors target mutations on the PIK3CA gene that can allow breast cancers with this mutation to grow.

• Alpelisib (Piqray) is approved to treat hormone receptor-positive, HER2-negative metastatic breast cancer in postmenopausal women and in men that tests positive for a PIK3CA mutation. It is taken as a daily pill. Possible side effects include skin rash, mouth sores, weight loss, fatigue, hair loss, and nausea and vomiting. Alpelisib can also be given to premenopausal women.

• Inavolisib (Itovebi) is a pill given with the targeted therapy palbociclib and the hormonal therapy fulvestrant. This treatment combination is approved for hormone receptor-positive, HER2-negative, PIK3CA mutation-positive advanced or metastatic breast cancer.

PARP inhibitors target enzymes that repair cancer cell DNA. The two medicines in this group are an option for people whose breast cancers are HER2-negative and who test positive for inherited BRCA1 or BRCA2 genetic mutations. Both can be taken as a pill. The side effects tend to be milder than other cancer treatments and may include nausea, headache, fatigue, diarrhea, lung inflammation, and infection.

• Olaparib (Lynparza)
• Talazoparib (Talzenna)

Tyrosine kinase inhibitors interfere with the HER2 protein’s ability to help cancer to grow. Lapatinib is a tyrosine kinase inhibitor approved to treat hormone receptor-positive, HER2-positive metastatic breast cancer along with the hormonal therapy letrozole.

Antibody-drug conjugates combine an antibody with a chemotherapy. The antibody targets specific proteins on cancer cells. Then, it brings the chemotherapy directly to the cancer cells to destroy them. This helps reduce the risk of damaging healthy cells.

There are four antibody-drug conjugates approved to treat breast cancer:

• Ado-trastuzumab emtansine (Kadcyla) is approved to treat HER2-positive breast cancer. It can treat breast cancer of any stage and any hormone-receptor status.
• Trastuzumab deruxtecan (Enhertu) is approved to treat metastatic breast cancer that is:
  • HER2-positive
  • HER2-low
  • Hormone receptor-positive and HER2-low
  • Hormone receptor-positive and HER2-ultralow
• Datopotamab deruxtecan (Datroway) is approved to treat hormone receptor-positive, HER2-negative metastatic breast cancer. This treatment targets a protein called Trop-2.
• Sacituzumab govitecan (Trodelvy) is approved to treat hormone receptor-positive, HER2-negative or triple-negative metastatic breast cancer. This treatment also targets the Trop-2 protein.

Chemotherapy

Many different chemotherapy medicines are used to treat hormone-receptor positive metastatic breast cancer. They are often used in combination with other therapies. Learn more about chemotherapy.

Radiation therapy

Radiation therapy is often used to manage symptoms or ease pain caused by cancer that has spread. Learn more about radiation therapy.

Clinical trials

You may also consider taking part in a clinical trial, a study that looks at how well new medical approaches work in people. Clinical trials offer access to new treatments that are not otherwise available and may prove to work better than standard treatments. Taking part in a clinical trial also helps researchers develop better treatments for those diagnosed in the future.