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.

Hormone receptor-positive metastatic breast cancer means that the hormones estrogen and/or progesterone help the cancer grow.

Receptors are proteins on the breast cancer cells. The cancer may have estrogen receptors (ER+), progesterone receptors (PR+), both (ER+/PR+), or neither. If the cancer also tests negative for the protein HER2, it is called triple-negative.

There are many effective treatments available for hormone receptor-positive metastatic breast cancer. Below, you can learn more about diagnosis, treatment options, and clinical trials looking at new potential treatments.

Diagnosing the cancer

Your care team uses many different tests to confirm a diagnosis of hormone receptor-positive, metastatic breast cancer. These can include imaging tests, blood tests, and tests on the breast cancer tissue.

Biopsy

If you were treated for early-stage hormone receptor-positive breast cancer in the past and it is now metastatic, talk with your medical oncologist about having a new biopsy of any abnormal finding from an imaging test. This is because it is possible for hormone receptor status to change, and it can change your treatment options.

Biopsy is also important if metastatic breast cancer is the first breast cancer diagnosis you have ever had (de novo metastatic breast cancer).

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

Biomarker testing

Whether this is a recurrence of a past breast cancer or a first-time diagnosis, it’s important to ask your doctor about biomarker testing. Biomarkers are cancer characteristics, such as proteins or gene mutations, that can help match a cancer to a treatment that targets the biomarker.

Biomarker testing can be done:

• After a new diagnosis of metastatic breast cancer
• Any time you and your care team are considering a new treatment

Visit Biomarker testing and Tests for metastatic breast cancer to learn more about different kinds of testing that can help you and your care team create the best treatment plan for you.

Treatment options

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 hormone receptor-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. Still, there are 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.
• If you have pain or bleeding, your surgeon might remove the original breast tumor to help ease your symptoms.

Hormonal therapy

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

• Premenopausal means that you are still having menstrual periods
• 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 have the option to switch from one to another over time if one medicine stops working against the cancer or if side effects are interfering with your daily life.

SERMs

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. It is available in pill or liquid form.
• Toremifene (Fareston) is FDA approved to treat metastatic breast cancer that is hormone receptor-positive or has an unknown receptor status. It is available in pill form. Although toremifene was used more in the past, it is rarely used now due to other treatment advances.

Aromatase inhibitors

Aromatase inhibitors may be given as a first treatment for metastatic breast cancer in postmenopausal women or premenopausal women taking GnRH agonists (ovarian suppression medicines). Aromatase inhibitors can also be given if other hormonal therapies stop working. Aromatase inhibitors include:

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

SERDs

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. 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 hormone receptor-positive 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.
• Imlunestrant (Inluriyo). Imlunestrant is given as two pills taken by mouth once a day. It is FDA approved to treat hormone receptor-positive, HER2-negative metastatic breast cancer that has an ESR1 mutation.

GnRH agonists

Gonadotropin-releasing hormone (GnRH) agonists temporarily stop the ovaries from producing estrogen. These ovarian suppression medicines are typically given to pre- and perimenopausal women in combination with tamoxifen, aromatase inhibitors, or fulvestrant.

Aromatase inhibitors and fulvestrant are only approved for use in postmenopausal women. However, taking a GnRH agonist makes it possible for pre- and perimenopausal women to take aromatase inhibitors or fulvestrant.

GnRH agonists are given by injection. They include:

• Goserelin (Zoladex)
• Leuprolide (Lupron)
• Triptorelin (Trelstar); this drug is not used as often as goserelin and leuprolide

Targeted therapy

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

CDK 4/6 inhibitors

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), taken in combination with an aromatase inhibitor or fulvestrant, or alone in some cases
• Palbociclib (Ibrance), taken in combination with an aromatase inhibitor or fulvestrant
  • If the cancer tests positive for a PIK3CA gene mutation, palbociclib can be taken in combination with the targeted therapy inavolisib (Itovebi) and fulvestrant. Inavolisib is currently only approved for people who have developed metastatic disease while taking hormonal therapy for early-stage breast cancer or within 12 months of finishing hormonal therapy for early-stage breast cancer.
• Ribociclib (Kisqali), taken in combination with an aromatase inhibitor or fulvestrant

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

low blood counts, headache, hair loss, fatigue, and decreased appetite.

AKT inhibitors

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 cancer’s ability to grow.

There is one AKT inhibitor approved to treat breast cancer: Capivasertib (Truqap). This drug is approved in combination with fulvestrant for hormone receptor-positive, HER2-negative metastatic breast cancer that tests positive for AKT1, PIK3CA, or PTEN mutations.

PI3K inhibitors

PI3K (phosphatidylinositol-3 kinase) inhibitors target mutations on the PIK3CA gene that can allow breast cancers with this mutation to grow.

• Alpelisib (Piqray) is approved in combination with fulvestrant 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.
• Inavolisib 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.
• Capivasertib is approved for hormone receptor-positive, HER2-negative metastatic breast cancer that tests positive for AKT1, PIK3CA, or PTEN mutations. It is given in combination with fulvestrant.

mTOR inhibitors

MTOR (mammalian target of rapamycin) 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. It is taken in combination with fulvestrant or exemestane. Everolimus is taken as a daily pill. Common side effects include cough, diarrhea, infection, mouth sores, and weakness.

PARP inhibitors

PARP, or poly (ADP-ribose) polymerase, 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)

ADCs

ADCs, also known as antibody-drug conjugates combine an antibody with a chemotherapy medicine. 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 hormone-receptor status.
• 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.
• Trastuzumab deruxtecan (Enhertu) is approved to treat metastatic breast cancer that is:
  • HER2-positive
  • HER2-low
  • HER2-ultralow
  • Hormone receptor-positive and HER2-low
  • Hormone receptor-positive and HER2-ultralow

TKIs

TKIs, also called tyrosine kinase inhibitors, interfere with the HER2 protein’s ability to help cancer to grow. If the breast cancer is metastatic and tests positive for HER2, there are three TKIs available:

• Tucatinib (Tukysa) is approved to treat metastatic, HER2-positive breast cancer. The cancer can be hormone receptor-positive or hormone receptor-negative. Tucatinib is given in combination with trastuzumab and the oral chemotherapy pill capecitabine (Xeloda).
• Lapatinib (Tykerb) is FDA approved to treat hormone receptor-positive, HER2-positive metastatic breast cancer in combination with the hormonal therapy letrozole.
• Neratinib (Nerlynx) is approved to treat metastatic, HER2-positive breast cancer of any hormone receptor status after two lines of previous treatment. Neratinib is given in combination with capecitabine.

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 want to consider talking with your care team about 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 might work better than standard treatments. Participating in a clinical trial also helps researchers develop effective treatments that can help others in the future.

Learn more about clinical trials for metastatic breast cancer. You can also search for trials with the Metastatic trial search tool.