HR+/HER2- Breast Cancer Treatment: How to Make Decisions With Your Doctor

According to the National Cancer Institute, hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer is the most common type of breast cancer in women. However, it can be a complex and challenging condition to treat. These types of tumors have hormone receptors (HR) for estrogen or progesterone, which support tumor growth. HER2 refers to a protein called human epidermal growth factor receptor 2, which causes cancer cells to grow quickly.

Many targeted therapies — which are less likely to impact healthy cells and cause fewer side effects than other cancer treatments — target HER2, but HER2- tumors don’t respond to these drugs. In addition, HR+/HER2- breast cancer generally doesn’t respond well to immunotherapy.

Yet effective treatments do exist. “There are always multiple options. You have to see what [patients] will be willing to do, but also follow the science,” says Laurie Matt-Amaral, MD, MPH, FACP, a medical oncologist at Cleveland Clinic Akron General in Ohio.

If you’re diagnosed with HR+/HER2- breast cancer, it’s important to work closely with your healthcare team to find the most effective treatment plan and ensure that it’s working for you. “Every step of the way in breast cancer treatment there is balance and open discussion,” says Erica L. Mayer, MD, MPH, a medical oncologist and clinical investigator at the Dana-Farber Cancer Institute in Boston.

How Your Doctor Will Work With You to Make Treatment Decisions

Your HR+/HER2- breast cancer treatment plan isn’t simply dictated by your healthcare provider. You have a critical role in reviewing the options and making the ultimate decisions. “For me, patients are involved 100 percent,” says Dr. Matt-Amaral. “People need to feel empowered to make decisions for themselves.”

People with breast cancer frequently have multiple treatment options at every stage — including early-stage cancer, and especially for metastatic cancer, which means the cancer has spread beyond the breast to other organs in the body. It’s also called stage IV cancer. “We are very fortunate to have many tools that are highly effective,” says Mayer.

After discussing the pros and cons of each individual treatment option, Matt-Amaral offers her recommendation, or the standard of care, to help patients in their decision. While most people go with their doctor’s recommendation because they trust their training and expertise, some opt not to do certain parts of therapy for various reasons, she adds.

To make an informed HR+/HER2- breast cancer treatment decision with your doctor, it’s important you understand your options and consider what factors are crucial to you.

Learn About the Treatment Options for HR+/HER2- Breast Cancer

The first and most critical step in making a treatment decision is understanding your available options. The treatment plan your doctor will recommend for HR+/HER2- breast cancer varies according to a number of factors, notably:

  • the stage and how fast a tumor is growing
  • your overall health and any other diagnosed conditions
  • whether or not you’ve gone through menopause
  • what other therapies you’ve tried, if it’s a recurrence

HR+/HER2- breast cancer treatments can cause side effects such as fatigue, nausea, and hair loss that impact quality of life. According to Mayer, with metastatic cancer in particular, therapies become less effective or stop working with time.

Each breast cancer drug is taken differently, notes Mayer. You might have to swallow a pill, or you might have intravenous (IV) therapy. And each drug is given at a specific interval, for a certain period of time. For example, some drugs are taken daily, weekly, or monthly; others may be given in cycles, with days or weeks off in between to allow your body to recover.

Your doctor will discuss your diagnosis and various treatment options with you. “Patients learn about the details of their disease, including the stage of disease, the subtype, the treatment landscape, the treatment options, the risks and benefits, and the side effect profile,” says Mayer.

With these details, Mayer recommends learning more by visiting a trusted cancer organization website with detailed and vetted information, such as the American Cancer Society (ACS), the Susan G. Komen Breast Cancer Foundation, or the American Society of Clinical Oncology.

Breast cancer treatments have evolved tremendously over the past several decades, with ongoing research impacting the available options. The following is a broad overview of the main types of treatments your doctor may discuss with you.

Surgery and radiation

Depending on the type of breast surgery you receive or depending on your cancer's characteristics, you may require radiation after surgery to keep the tumor from coming back. In some cases, it’s possible to remove just the tumor and keep other breast tissue. This is known as breast-conserving surgery. Other times, mastectomy — or complete removal of the breast—may be necessary, according to the ACS.

Hormone therapy

HR+ breast cancer grows and spreads in part thanks to hormones including estrogen and progesterone. Most hormone therapies reduce the level of estrogen in the body or the ability of estrogen to support tumor growth, says the ACS.

All hormone therapies can cause various side effects, such as hot flashes, bone pain, joint stiffness, or nausea. Some may cause rare but more serious potential side effects, such as bone thinning in premenopausal women, endometrial cancer, or cataracts. Hormone therapy also tends to become less effective over time.

Some of the most common hormone therapies for HR+/HER2- breast cancer include:

  • Selective estrogen receptor modulators (SERMs). Tamoxifen and toremifene (Fareston) block estrogen from attaching to a tumor’s hormone receptors.
  • Selective estrogen receptor degraders (SERDs). Fulvestrant works by breaking down estrogen receptors throughout the body.
  • Aromatase inhibitors (AIs). Letrozole (Femara), anastrozole (Arimidex), and exemestane (Aromasin) stop the body from producing estrogen.
  • Ovarian suppression. These treatments shut down the ovaries of premenopausal women — essentially inducing menopause either temporarily or permanently. The ACS says options include surgery to remove the ovaries or drugs such as leuprolide (Lupron).


In some cases, doctors may recommend chemotherapy. Chemotherapy may be used after surgery as well as before in order to shrink the tumor so it’s possible to conserve the breast.

Chemotherapy can cause a number of side effects depending on the drug such as hair loss, mouth sores, nausea, nerve damage, fatigue, fertility issues, and heart damage, according to the Cleveland Clinic.

Targeted therapies

Targeted therapies are directed at specific proteins on cancer cells, effectively killing these cells or slowing their growth. They’re often used alongside hormone therapies and can sometimes even make these drugs more effective.

The downside of these therapies is they can cause side effects such as nausea, mouth sores, anemia, increased risk of infections, or hair loss, according to the ACS. Less often, some drugs have been linked to more severe side effects, such as serious infections, life-threatening inflammation of the lungs, increased blood sugar levels, or some types of blood cancer.

For HR+/HER2- breast cancer, examples of common targeted therapies include:

  • CDK4/6 inhibitors. Abemaciclib (Verzenio), palbociclib (Ibrance), and ribociclib (Kisqali) block certain proteins in cancer cells, known as cyclin-dependent kinases (CDKs), to keep cells from dividing.
  • mTOR inhibitors. Everolimus (Afinitor, Zortress) keeps tumors from creating new blood vessels and by blocking mTOR, a protein that encourages cell growth and division.
  • PI3K inhibitors. Alpelisib (Piqray) can be used to treat breast cancer with a PIK3CA gene mutation.
  • PARP inhibitors. Women with a BRCA mutation may take Olaparib (Lynparza) or talazoparib (Talzenna) to treat cancers by blocking the protein PARP, or poly(ADP-ribose) polymerase.
  • Antibody-drug conjugates. Sacituzumab govitecan (Trodelvy) works by using antibodies that attach to and destroy cancer cells.

Review Next Steps

If you have metastatic breast cancer, Matt-Amaral says she informs patients from the earliest discussions that all therapies are palliative — meaning they help treat symptoms and improve quality of life, but won’t cure the disease. “I tell them that their cancer will progress at some point, and then we will need to change treatment at some time in the future,” she says.

Treatments for metastatic cancer are continuous and given for as long as they’re working, explains Mayer. Throughout, patients are monitored with screening tests, labs, and physical exams.

If the medicines are stabilizing or shrinking the cancer, you’ll continue with the same treatment plan. If there’s definitive evidence that the cancer is worsening despite ongoing treatment, your doctor will work with you to determine the best next option. “Each step of the way, the patient and the provider decide what would be the best fit for the person based on what’s going on in terms of the disease, the side effects, and their values,” says Mayer.

Consider Your Values and Preferences

Armed with this information, it’s up to you to consider what treatments work best for you based on your values and preferences. “Together, a patient and provider make decisions that will hopefully and optimally best serve the person in terms of not only helping with outcomes related to the cancer but also having a favorable impact on their quality of life,” says Mayer.

People with breast cancer sometimes hesitate to take some treatments, figuring they’ll run the risk of recurrence rather than deal with potential unpleasant side effects. Matt-Amaral aims to convince her patients to at least try the therapy first before completely writing it off. “Some women try treatments and say they tolerate them and are glad they tried. Others try and cannot tolerate them, so they stop,” she says. Either way, your doctor should be there to counsel you on your next options.

Discuss Whether a Clinical Trial Is Possible

You don’t have to be diagnosed with advanced or metastatic cancer to participate in a study for a new drug. Clinical trials are available for patients with breast cancer at any stage, starting with the initial diagnosis. “At every step in the journey, there often can be a trial option that is looking to optimize or improve the standard-of-care choice,” says Mayer.

It’s important for you and your doctor to discuss if any clinical trials could be a good fit for you.

Your doctor may recommend a trial if you’ve run out of medication options or if there’s an open trial for a specific marker that’s applicable to you, says Matt-Amaral.

Keep in mind that clinical trials are designed by teams of doctors and researchers and have gone through rigorous vetting by independent regulatory boards before they’re open to patients. “As providers, we would never offer a trial to a patient that we felt would in any way expose them to something that was inferior to the standard of care,” says Mayer. In addition, your doctor will follow your progress closely. “If there’s any sense that things are not going in the right direction, then it’s picked up on quickly and allows time to change gears,” she adds.

It’s thanks to these trials that researchers have made remarkable progress in breast cancer treatments over the years. “None of this work could have been possible without the participation of patients in clinical trials,” says Mayer.

Get a Second Opinion if Necessary

If you have any questions or concerns, make sure to talk with the doctors and nurses on your team so they understand how to provide you with the best possible care. You should always feel informed and comfortable with your treatment decision. If not, you can always ask for a second opinion from another cancer care team to feel more confident and reassured.

“I usually tell patients to just let me know, so that I can be aware that a records request may be coming,” says Matt-Amaral. “No good doctor is ever going to fault you for getting another opinion.”

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