Breast CancerLiving With HR+/HER2– Metastatic Breast Cancer

Understanding Your HR+/HER2- Metastatic Breast Cancer Treatment

Talking to Your Oncologist About HR+/HER2- Metastatic Breast Cancer Treatment

Not all metastatic breast cancers are treated the same way. For those living with HR-positive/HER2-negative metastatic breast cancer, the best course of action is to talk openly with their care team about testing, therapies, and clinical trials that
Talking to Your Oncologist About HR+/HER2- Metastatic Breast Cancer Treatment

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How Metastatic Breast Cancer Treatment Affects Your Emotional Well-Being

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Metastatic Breast Cancer Progression: Defining Treatment Goals and Next Steps

Metastatic Breast Cancer Progression: Defining Treatment Goals and Next Steps00:03:26
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Published on May 16, 2025
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Not all metastatic breast cancers behave similarly in the body. Each subtype of breast cancer has distinct characteristics, which make them more likely to behave in certain ways and respond to certain treatments.

The cells in HR-positive/HER2-negative breast cancer have receptors for the hormones estrogen and progesterone. Because these hormones help fuel the growth of the tumor, your treatment plan will likely include endocrine therapy, which can suppress estrogen and progesterone levels in the body.

Conversely, HR-positive/HER2-negative breast cancer cells lack HER2 proteins, which help breast cells grow and repair themselves. While there are treatments available that can target the HER2 protein, they won’t work on HER2-negative breast cancers.

Your oncologist may also order germline testing (genetic testing) that looks for certain mutations in your DNA. The results of these tests can predict how well you’ll respond to certain treatments, says Hanna Irie, MD, PhD, an oncologist at Mount Sinai Hospital in New York and associate professor of medicine and oncological sciences at the Icahn School of Medicine at Mount Sinai.

 (The mutations PIK3CA and ESR1, for example, have been linked to endocrine therapy resistance.)

Germline testing isn’t always widely available, so if it isn’t offered to you, Dr. Irie recommends talking to your oncologist and asking if the test is right for you.

The genetic makeup of the cancer is just one component of your treatment plan. Your age, life goals, and personal preferences will also play a role in determining which treatment works best for you.

Treatment Options for HR+/HER2- Metastatic Breast Cancer

Currently, HR-positive/HER2-negative metastatic breast cancer is treated with a combination of endocrine therapy and a CDK4/6 inhibitor, Irie says. Depending on the results of your germline testing and other factors, other treatments may be used as well.

Here are a few treatments you may receive:

Endocrine Therapy Premenopausal women will likely receive ovarian suppression, which prevents the ovaries from making estrogen. Ovarian suppression can be done surgically by removing the ovaries (oophorectomy) or with medications given by injection.

After menopause, the ovaries have already stopped producing most estrogen, so surgery isn’t effective. In this case, endocrine therapy is given by medication, including aromatase inhibitors, selective estrogen receptor modulators, and selective estrogen degraders.

Targeted Therapy Endocrine therapy is often paired with a CDK4/6 inhibitor — a type of targeted therapy medication. CDK4/6 inhibitors target specific proteins called cyclin-dependent kinases 4 and 6, which are responsible for helping the cancer cells divide and multiply.

Breast cancers with a PIK3CA gene mutation can sometimes be treated with a medication called a P13 kinase inhibitor.

Chemotherapy Sometimes HR-positive/HER2-negative breast cancer is treated with chemotherapy — drugs that help prevent the cancer cells from growing and multiplying.

Antibody-Chemotherapy Drug Conjugates These drugs are made of an antibody therapy, which targets certain cancer cells, and a chemotherapy drug, which prevents cancer cells from growing and multiplying.

Clinical Trials for Metastatic Breast Cancer

If you have limited treatment options available, you may want to consider joining a clinical trial, which tests the effectiveness of new treatments. Your doctor may bring it up, but you don’t have to wait for them to broach the subject, so don’t hesitate to ask questions, says Irie.

“Clinical trials can offer access to the latest, most innovative treatments,” she says. To learn more about active trials, visit clinicaltrials.gov.

Irie also recommends getting a second or even third opinion from an oncologist at a different institution. Telehealth services, she adds, allow you to meet with doctors who don’t live near you. Getting these additional opinions can not only help you learn about other clinical trials, but they can also expose you to more information that may be helpful in the future.

Most importantly, keep the line of communication open with your care team. Talk to your doctors about the current metastatic breast cancer treatments and how they might fit into your plan.

The Takeaway

  • Biomarker testing and genetic testing can help you understand how your breast cancer behaves. It can also guide you toward the best treatment options.
  • Several medication options are available to treat HR-positive/HER2-negative metastatic breast cancer, but, depending on your biomarker and germline testing, some may be better for you than others.
  • Research on HR-positive/HER2-negative breast cancer is ongoing, and new treatment options are always in the pipeline. Engage in open discussions with your doctor about possible emerging treatments or clinical trials that may be a good fit for you.
EDITORIAL SOURCES
Everyday Health follows strict sourcing guidelines to ensure the accuracy of its content, outlined in our editorial policy. We use only trustworthy sources, including peer-reviewed studies, board-certified medical experts, patients with lived experience, and information from top institutions.
Resources
  1. Biomarker Tests and Cancer Treatment. American Cancer Society. September 21, 2022.
  2. Treatments for Metastatic Breast Cancer. Susan G. Komen. February 19, 2025.
  3. DePolo J. ASCO and SSO Update Genetic Testing Guidelines for People With Breast Cancer. Breastcancer.org. April 30, 2024.
  4. Tolaney SM et al. Clinical Significance of PIK3CA and ESR1 Mutations in Circulating Tumor DNA: Analysis From the MONARCH 2 Study of Abemaciclib Plus Fulvestrant. Clinical Cancer Research. April 15, 2022.
  5. Ovarian Suppression. Susan G. Komen. March 3, 2025.
  6. Hormone Therapy for Metastatic Breast Cancer. Susan G. Komen. February 21, 2025.
  7. Conner K. What Are CDK4/6 Inhibitors? Breastcancer.org. January 13, 2025.
  8. P13 Kinase and AKT Inhibitors for Metastatic Breast Cancer. Susan G. Komen. February 20, 2025.
  9. Chemotherapy for Metastatic Breast Cancer. Susan G. Komen. February 19, 2025.
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Lisa D. Curcio, MD, FACS

Medical Reviewer
Castle Connolly Top Doctor
Lisa Curcio, MD, is a board-certified general surgeon and a fellowship-trained surgical oncologist. She is currently the medical director of breast surgery at Northern Dutchess Hospital in Rhinebeck, New York. Dr. Curcio attended George Washington University Medical School in Washington, D.C., where she also completed a residency in general surgery. She was invited to fellowship training in cancer surgery at City of Hope National Medical Center in Duarte, California. She was the recipient of the competitive U.S. Air Force Health Professions Scholarship Program. During her military commitment, Dr. Curcio served in the military as chief surgical oncologist at Keesler Medical Center in Biloxi, Mississippi. 

From 2003 to 2004, she served as program director for Susan G. Komen in Orange County and remains involved with Komen outreach efforts. She was on the board of Kids Konnected, a nonprofit that helps children of cancer patients deal with the emotional fallout of a cancer diagnosis. Currently, she is on the board at Miles of Hope Breast Cancer Foundation, an organization dedicated to providing support services for people affected by breast cancer in New York's Hudson Valley. Dr. Curcio also has a strong background in breast cancer research, having contributed to dozens of peer-reviewed articles. She is currently a member of the Alpha Investigational Review Board.

Her practice includes benign and malignant breast diagnoses. Dr. Curcio was diagnosed with breast cancer at the age of 37. Although her fellowship training was in surgical oncology, this experience motivated her to provide compassionate, high level breast care and to focus on breast surgery.

Dr. Curcio is passionate about treating the patient and individualizing the care plan to their specific needs. Dr. Curcio strongly believes that cancer care must include lifestyle changes to focus on healthier habits to reduce future events. Her practice also focuses on breast cancer risk reduction, education, and access to genetic testing for patients with a family history of breast cancer.
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Amy Gragnolati

Amy Gragnolati, PharmD, BCPS

Author

Amy Gragnolati, PharmD, BCPS, is a clinical pharmacist and medical writer. She is board certified in pharmacotherapy and holds her pharmacist license in Georgia and California.

After completing her education at the University of Georgia, she worked as a clinical pharmacist at the University of California San Francisco Benioff Children’s Hospital, specializing in pediatric intensive care, oncology, and cardiac care. She then worked at Kaiser Permanente San Francisco in addiction medicine and adult family medicine. After five years at Kaiser, she worked as a pharmacy editor at GoodRx for four years.

Outside of work, Amy enjoys yoga and has her registered yoga teacher certification. She’s also an avid baker and cook, and loves hosting friends and family for a big meal. On weekends, you can typically find her outside enjoying nature with her husband and kids.

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