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HR-Positive HER2-Negative Metastatic Breast Cancer: Treatments and Tests

HR-Positive HER2-Negative Metastatic Breast Cancer: Treatments and Tests

This article is for people who have hormone receptor (HR)-positive HER2-negative metastatic breast cancer (MBC), or their care partners, as well as others who want to learn more about HR-positive HER2-negative MBC. The goal is for patients to better understand available treatments and tests for HR-positive HER2-negative MBC that can help guide care.

You will learn about:

  • Tests to help determine MBC treatment

  • Treatments for HR-positive HER2-negative MBC

  • Differences in treatment if you are premenopausal or postmenopausal

  • Making a treatment plan with your doctor

  • Follow-up testing for continued care and to track how treatment is working

  • Questions to ask your doctor

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Your Hormone Receptor (HR) Status

Knowing your HR status is important when you have MBC.

Breast cancer cells taken out during a biopsy or surgery will be tested to see if they have receptors (proteins) for the hormones estrogen and progesterone. Breast cancer is HR-positive if the tumor cells have a large number of receptors for estrogen, progesterone, or both.

About two-thirds of women with breast cancer have tumors that have hormone receptors.

Knowing Your HER2 Status

Your HER2 status is also important to determine MBC treatment.

Breast cancer tissue is tested for HER2, a gene that makes HER2 proteins. These proteins are receptors that help control the growth and repair of breast cells.

HER2-negative breast cancer has tumor cells that contain little or none of the HER2 receptor. Because of this, these cells tend to grow more slowly.

About half of all MBCs are both HR-positive and HER2-negative.

Getting Tested for a`nbsp;BRCA`nbsp;Mutation

Knowing if you have an inherited BRCA mutation (change) is valuable when treating HER2-negative MBC.

Everyone has genes called BRCA1 and BRCA2. Normal BRCA genes help prevent tumor growth. But some people have an inherited mutation in one or both of these genes that increases their risk of developing breast cancer.

Mutated BRCA genes can also affect what treatment or medicines may be right for you.

A blood or saliva test can check for a BRCA1 and BRCA2 mutation. You can talk to your doctor about if you should have this test and the possible results.

What Treatments Are Available?

You may receive hormone therapy -- also called endocrine therapy -- for your HR-positive HER2-negative MBC. Hormone therapy helps stop cancer cells from getting the hormones they need to grow.

Which hormone therapy is right for you will depend on your menopausal status and past treatment, if any, for breast cancer.

Hormone therapy may include surgery (removal of the ovaries) for certain women, as well as medicine such as:

  • Luteinizing hormone-releasing hormone (LHRH) agonists

  • Aromatase inhibitors (AIs)

  • Antiestrogen medicines called selective estrogen receptor modulators (SERMs) or selective estrogen receptor degraders (SERDs)

Other Treatments

Treatments such as chemotherapy and radiation can shrink or slow the tumor growth or ease symptoms of cancer.

Your doctor may also prescribe other medicines to help treat your MBC, such as:

  • CDK4/6 inhibitors, used alone or with hormone therapy

  • mTOR inhibitors, which may be used with hormone therapy

  • PARP inhibitors, which can help chemotherapy kill cancer cells

Menopause Status Can Affect Treatment

Your treatment will depend on your menopausal status (whether or not you have gone through menopause).

If you still get your period (premenopause), your treatment will help lower estrogen and progesterone levels and may include:

  • Surgery

  • LHRH agonists

  • SERMs

If you have already gone through menopause (postmenopause), treatment may include:

  • AIs

  • SERMs or SERDs

  • CDK4/6 inhibitors

  • mTOR inhibitors

Chemotherapy can be used no matter what your menopausal status is (premenopause or postmenopause).

Making a Plan With Your Doctor

The main goals of MBC treatment are to slow or stop growth of the disease, while easing symptoms and side effects and maintaining your quality of life.

There are many treatments for MBC. The plan you create with your doctor and cancer care team will be based on:

  • HR and HER2 status

  • BRCA mutation status

  • Menopausal status

  • Where the cancer has spread

  • Your symptoms and side effects

  • Past breast cancer treatments

  • Other medical conditions you may have

  • Personal needs you may have that can affect treatment decisions, such as your support system

Follow-Up Tests to Help Guide Treatment

Your doctor will run tests every few months to see how well treatment is working and check on symptoms and side effects.

Tests may include:

  • Physical exam

  • Performance status (a measure of how well you can keep up with your daily activities)

  • Blood tests for cancer growth, liver function, and proteins that show if treatment is working (tumor markers)

  • Imaging tests (X-ray, CT scan, PET scan, or bone scan)

Sometimes your medicines may stop working and your doctor may need to change your dose or treatment. But if treatment is working and the side effects can be managed, your treatment may stay the same. Talk to your doctor about what side effects you may experience, when to report them, and how they can be managed.

Questions to Ask Your Doctor

You may want to ask your doctor questions about your treatment, such as:

  • What tests will I need?

  • What treatments are available?

  • How will I know if treatment is working?

  • What are possible side effects and how can I manage them?

  • When should I tell you about symptoms or side effects?

  • Will I need to change my eating habits?

  • Are there any limits on what I can do?

  • Can I exercise during treatment? If so, what kind and how often?

  • Can you recommend a palliative care specialist to help me with symptoms and my quality of life?

  • What should I do if I start to feel overwhelmed, depressed, or distressed?

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Authors and Disclosures

Clinician Reviewer

Susan L. Smith, MN, PhD

Senior Medical Education Strategic Director, Medscape, LLC

Disclosure: Susan L. Smith, MN, PhD, has disclosed no relevant financial relationships.


Heather Lewin, MAT

Senior Scientific Content Manager, Medscape, LLC

Disclosure: Heather Lewin, MAT, has disclosed no relevant financial relationships.


Anita A. Galdieri, RPh, PharmD

Senior Scientific Content Manager, Medscape, LLC

Disclosure: Anita A. Galdieri, RPh, PharmD, has disclosed no relevant financial relationships.


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