Plan Your HR+/HER2- MBC Treatment: Key Questions for Your Doctor
CancerBreast Cancer

Planning Ahead With HR+/HER2- MBC: Questions to Ask Your Doctor About Treatment Progression and What Comes Next

Planning Ahead With HR+/HER2- MBC: Questions to Ask Your Doctor About Treatment Progression and What Comes Next
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Published on December 10, 2025
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When you get an HR+/HER2- metastatic breast cancer (MBC) diagnosis, it can feel like your future is out of your hands. Treatment for this type of cancer targets certain receptors on cancer cells, and the various combinations and options may seem overwhelming at first.

Hormone receptor–positive (HR+) breast cancer cells have receptors for the hormones estrogen, progesterone, or both, which help them grow. Treatments for this type of cancer stop these hormones from attaching to these receptors or reduce hormone levels to starve the cancer cells.

 When breast cancer is HER2-negative, it means the cells don’t have (or have very few) receptors for a protein called human epidermal growth factor 2 (HER2). Cancer treatments that target HER2 receptors will not be effective for this type of breast cancer.

“There are a lot of therapy options available for HR+/HER2- MBC,” says Azka Ali, MD, a breast medical oncologist at Cleveland Clinic in Ohio. “But treatments may often work for some time and [then the] cancer may become resistant.” Once this happens, your oncologist may recommend a change in treatment, and it can help to know your options ahead of time.

No matter how well your HR+/HER2- MBC treatment is working, you can regain a sense of control by planning ahead and preparing a list of informed, proactive questions about your current treatment, next steps, the potential role of clinical trials, and how you can balance your therapy with quality of life.

Questions to Ask About Your Current MBC Treatment

It’s important to understand your current treatment: how it works, its timeline, and what side effects you should expect. “With HR+/HER2- metastatic breast cancer, patients will [first] be offered treatment options consisting of endocrine therapy, including an aromatase inhibitor in combination with a class of drugs known as CDK4/6 inhibitors,” says Dr. Ali.

Endocrine (hormone) therapies and aromatase inhibitors block the production of estrogen, while CDK4/6 inhibitors prevent cancer cells from multiplying.

The following CDK4/6 inhibitors are used to treat HR+ metastatic breast cancer:

  • abemaciclib (Verzenio)
  • palbociclib (Ibrance)
  • ribociclib (Kisqali)
Aromatase inhibitors lower estrogen levels in the body and include these options:

  • anastrozole (Arimidex)
  • exemestane (Aromasin)
  • letrozole (Femara)
If you haven’t yet gone through menopause, your oncologist may also recommend other treatments to stop your ovaries from producing estrogen, such as chemotherapy, luteinizing hormone-releasing hormone (LHRH) agonists, or surgery to remove the ovaries.

At your next appointment, you can ask these questions about your current MBC treatment:

  • How does my treatment work?
  • How long will the treatment take?
  • What are its benefits and risks?
  • What side effects can I expect?
  • How can I maximize my quality of life during this time?
  • What dietary precautions should I take?
  • How can I support bone health during treatment?
  • What symptoms should I notify you of?
  • What are some signs it’s working or not working?
  • What kind of prognosis can I expect with this treatment?
  • What follow-up tests or monitoring will I need?
  • What happens if it doesn’t work?

Questions to Ask About the Next Line of Therapy

Even if your provider expects your current treatment to work well, it’s a good idea to understand the next possible phase. “Planning ahead and knowing what to expect next makes patients better prepared and less anxious,” says Adriana Kahn, MD, a medical oncologist at Smilow Cancer Hospital and breast cancer researcher for Yale Cancer Center.

“When patients are in need of treatment change, the selection of treatment depends on how well patients may have responded to their first-line treatment,” says Ali. “If patients remain on endocrine therapy with CDK4/6 inhibitors for at least 12 months or longer, treating oncologists may feel that cancer may still benefit from additional endocrine therapy–like treatments.”

If your first treatment regimen doesn’t work or stops working, your oncologist may recommend another type of hormone therapy with different medications, depending on a few factors, such as genetic mutations.

Breast cancer can develop from different genetic mutations, and about 28 percent of people with HR+/HER2- MBC have a mutation in the PIK3CA gene.

 Sometimes mutations can arise during treatment with aromatase inhibitor therapy, which can affect not only PIK3CA, but also the estrogen receptor gene (ESR1).

As soon as your treatment has stopped working or the cancer has progressed, the American Society of Clinical Oncology recommends testing for ESR1 mutations.

 Your oncologist may order molecular profiling tests to look for ESR1 or PIK3CA gene mutations.

 This testing can be done through a tissue biopsy or by looking for this DNA in your blood (liquid biopsy).

If your initial therapy included aromatase inhibitors like letrozole (Femara) or anastrozole (Arimidex), your oncologist may recommend one of the following therapies that block estrogen receptors:

  • Another AI called exemestane (Aromasin), paired with a targeted drug like everolimus (Afinitor)
  • A selective estrogen receptor degrader (SERD) like elacestrant (Orserdu), imlunestrant (Inluriyo), or fulvestrant (Faslodex)
  • A different aromatase inhibitor with a CDK4/6 inhibitor
When you develop a PIK3CA gene mutation during treatment, your provider may suggest fulvestrant (Faslodex) with a PI3K inhibitor like alpelisib (Piqray) or inavolisib (Itovebi). For other gene mutations like AKT1 or PTEN, fulvestrant (Faslodex) with capivasertib (Truqap) may work better.

For cancer that has stopped responding to hormone treatment completely, you may need to try another option, such as chemotherapy, immunotherapy, or PARP inhibitors, which prevent cancer cells from repairing themselves.

All these options can feel overwhelming, but your provider can help you decide on the best path forward. To better understand your future HR+/HER2- MBC treatment options, you can ask these questions:

  • What tests will I need to decide on my next treatment (such as molecular profiling or liquid biopsy to look for ESR1 or PIK3CA mutations)?
  • How will this treatment work?
  • What are its benefits and risks?
  • How long is the course of this treatment?
  • When, where, and how often will treatments take place?
  • What kind of prognosis can I expect with this treatment?
  • What follow-up tests or monitoring will I need?
  • What happens if it doesn’t work?

Questions to Ask About Clinical Trials

Current approved treatments aren’t your only choices when you have HR+/HER2- MBC — you can also ask your provider about clinical trials. Most established treatments were in trials not long ago, and many people who took part not only got better treatment early, they also helped establish therapies that now help millions of others, says Dr. Kahn.

Currently clinical studies for HR+/HER2- MBC are testing the success of new treatments like gedatolisib and ECI830, both on its own and in combination with ribociclib (Kisqali) and fulvestrant (Faslodex).

 Another trial is assessing how well samuraciclib and elacestrant (Orserdu) work together for this type of advanced breast cancer.

Emerging treatments for HR+/HER2- MBC have helped people with this cancer type live longer, and taking part in clinical trials can put you at the forefront of this progress.

 “Most current clinical trials are targeted and very effective, with well-monitored risks of toxicities for early intervention,” says Kahn. No treatment or trial is without risk, but new experimental therapies can improve both survival and quality of life, Kahn says.

If interested, you can ask these questions about clinical trials:

  • How will I know if I’m ready or eligible to participate in a clinical trial?
  • What’s involved in joining a clinical trial?
  • Where will the trial take place and at which hospital location?
  • Is it available at a satellite location close to home?
  • What expectations should I have for prognosis or outcome?
  • How can I find recruiting trials?
  • What would happen if the trial treatment does not work?

Questions to Ask About Maintaining Quality of Life

HR+/HER2- MBC has no cure, but treatment can slow cancer growth and improve symptoms.

 Unfortunately, MBC treatment can also cause unpleasant side effects, such as hot flashes, mood swings, nausea, fatigue, diarrhea, and liver complications.

It’s important to balance overall survival with quality of life. If side effects from your current treatment are affecting your quality of life too much, you can discuss a change in treatment with your provider.

 Palliative care teams can help you navigate these decisions and live well throughout your treatment.

Kahn also recommends seeking out supportive care services, social workers, patient advocacy groups, peer groups, and lifestyle changes for better health throughout treatment. One study review found that people with MBC experienced the most improvement in quality of life when they participated in support groups or peer mentoring at least one or more times per week.

The balance between how aggressively you treat HR+/HER2- MBC and quality of life is yours to decide. If you want to talk to your provider about prioritizing quality of life, here are some questions you can ask:

  • What does it mean to prioritize quality of life over treatment?
  • Will my treatments slow down or stop?
  • Is there another treatment I can try that might improve my quality of life?
  • How will this shift in priorities change my prognosis and timeline?

The Takeaway

  • A metastatic breast cancer diagnosis can feel disorienting, but by planning ahead you can regain a sense of control.
  • The best way to plan for your future with MBC is to have questions ready for your cancer specialist visit.
  • You can ask your oncologist questions about your current treatment, possible future treatments, clinical trials, and prioritizing quality of life.

Resources We Trust

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
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  5. CDK4/6 Inhibitors. Susan G. Komen. February 27, 2025.
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Lisa D. Curcio, MD, FACS

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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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Abby McCoy is an experienced registered nurse who has worked with adults and pediatric patients encompassing trauma, orthopedics, home care, transplant, and case management. She is a married mother of four and loves the circus — that is her home! She has family all over the world, and loves to travel as much as possible.

McCoy has written for publications like Remedy Health Media, Sleepopolis, and Expectful. She is passionate about health education and loves using her experience and knowledge in her writing.

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