Treatment for HR+/HER2- metastatic breast cancer (mBC) usually involves one or more types of systemic therapies. These are drug-based treatments that go through your entire body rather than zeroing in on a specific tumor. For HR+/HER2- mBC, your doctor may suggest targeted therapy, endocrine therapy, genomics-guided immunotherapy, or a combination of these treatments. These therapies may also be used with traditional cancer treatments, such as chemotherapy, radiation therapy, and surgery.
As with any powerful treatment, side effects can accompany these HR+/HER2- mBC therapies. Side effects can range from temporary bouts of nausea to heart problems. Learning about HR+/HER2- mBC treatment side effects may help you better prepare for them and know how to manage them if they happen. This can make this part of your journey a little easier.
What Is HR+/HER2- Metastatic Breast Cancer?
HR+/HER2- mBC refers to breast cancer that has spread (metastasized) to other parts of the body. HR stands for hormone receptor — proteins (receptors) on the cancer cells that bind to a particular hormone. For this type of cancer, the cells have receptors for estrogen and/or progesterone.
HER2 stands for human epidermal growth factor receptor 2 — a protein that regulates the growth, division, and repair of cells. HER2-, also called HER2-negative, means the cancer cells don’t have high levels of HER2.
Treatments and Side Effects
Your doctor will recommend a particular treatment plan based on several things. Among them are where in your body the cancer has spread and its HR and HER2 status. Your response to previous treatments and other health factors also may be considered.
When cancer has metastasized to other other organs and is not isolated to a particular tumor, systemic treatments are usually necessary. These treatments can trigger some unpleasant and uncomfortable side effects. In many cases, the side effects will ease in between treatments or once treatment ends. Some may linger, however, so be sure to get a good idea what to expect before treatment begins.
Targeted therapy
The goal of targeted therapy is to destroy cancer cells while sparing healthy cells. Your doctor does this by identifying genetic changes or mutations in the body that turn healthy cells into cancerous ones and then administering drugs that either kill the cancerous cells or interfere with the process they use to multiply.
Targeted therapy drugs include pills, shots, and intravenous (IV) solutions. The duration and type of targeted therapy will depend largely on the nature of your cancer.
Targeted therapy side effects vary depending on the type of drug used and the way an individual responds to treatment. Some of the more common side effects include:
- Black or tarry stool, or red blood in your stool, caused by bleeding in the stomach or intestines
- Blood clots
- Diarrhea
- Hair color loss
- Heart arrhythmia (abnormal rhythm) or other heart problems
- High blood pressure
- Slow wound healing
Endocrine therapy
Endocrine therapy is also known as hormone therapy. Most types of endocrine therapy either bring down your estrogen levels or interfere with estrogen’s role in the spread of cancer cells.
One commonly used drug is tamoxifen (Nolvadex, Soltamox), which is a selective estrogen receptor modulator (SERM) that blocks estrogen from binding to cancer cells. Another SERM used in endocrine therapy for HR+ HER2- mBC is toremifene (Fareston).
SERM side effects include:
- Hot flashes
- Menstrual cycle changes
- Vaginal dryness or discharge
Rarely, serious side effects can occur with the use of SERMs including an increased risk of blood clots and in women who have gone through menopause an increased risk of endometrial cancer.
Similar to SERMs are selective estrogen receptor degraders (SERDs), which help slow or stop the spread of cancer by making the estrogen receptors unable to bind to estrogen.
Side effects of the SERDs elacestrant (Orserdu), fulvestrant (Faslodex), imlunestrant (Inluriyo), and vepdegestrant (Veppanu) include:
- Fatigue
- Headaches
- Hot flashes or night sweats
- Joint and muscle pain
- Loss of appetite
- Nausea
Drugs that lower estrogen levels are known as aromatase inhibitors, and they include anastrozole (Arimidex), exemestane (Aromasin), and letrozole (Femara). Their side effects include:
- Bone and joint pain
- Hot flashes
- Muscle pain
- Vaginal dryness
Genomics-guided immunotherapy
Genomics-guided immunotherapy is sometimes used in the treatment of a certain type of advanced breast cancer that has genetic changes called mismatch repair deficiency. Solid tumors that are mismatch repair deficient are sometimes treated with an immunotherapy drug called dostarlimab (Jemperli).
Side effects occur when the immune system is activated and begins to attack healthy cells. Some common side effects include:
- Chills
- Diarrhea
- Dizziness
- Fatigue
- Fever
- Heart palpitations
- Muscle and joint pain
- Nausea
- Sinus infection
- Trouble breathing
Radiation therapy
Radiation therapy may be used at most stages of breast cancer treatment. For metastatic breast cancer, radiation may help ease symptoms that develop in other parts of the body.
Common side effects may include:
- Breast swelling
- Fatigue
- Skin irritation, such as redness and blistering
Surgery
Breast cancer surgery may involve removal of the tumor — a procedure known as a lumpectomy (partial mastectomy) — or removal of the entire breast (mastectomy). More surgeries involving nearby lymph glands also may be necessary. Surgery isn’t always used in cases of metastatic breast cancer but may be appropriate to prevent or treat symptoms or complications.
Possible surgery side effects include:
- Blood clots
- Hematoma (a clot from a broken blood vessel)
- Numbness
- Seroma (a buildup of fluid around the surgery area)
- Shoulder stiffness
- Wound infection
Have a Plan
You may not be able to predict exactly how HR+/HER2- mBC treatment side effects will make you feel or affect your everyday life or long-term future. As you go through HR+/HER2- mBC treatment, you may find that your energy levels change from day to day. Your mobility and ability to do the things you used to do may change over time.
Before you hit the uncertainty and “good days, bad days” routine, you can develop a plan to help you get through treatment and beyond.
Talk with your health care team about your upcoming treatment schedule and what you can expect. Try to get an idea of how treatment might affect your appetite, energy levels, sleep, mood, etc., and think about what changes you may have to make with your diet, work, household and family responsibilities, and more.
Include family and friends in your planning. If there is ever a time to rely on loved ones, this is it. By including them in your care and asking for help with transportation, grocery shopping, chores, and other needs, you not only ease the burden on yourself, but you allow them to overcome their feelings of helplessness by assisting you.
Anticipate hair loss and other changes. Some side effects may be very upsetting, but planning for them now may give you a greater feeling of control. Talk with experts and cancer survivors or do some research about wigs, clothes, and other things that may make you feel less self-conscious and more confident. Talk with your insurance about whether wigs, canes, or other devices you may want or need are covered.
Report Concerning Side Effects
Some side effects may last for a short time and be more of an annoyance than a serious interference with your well-being and day-to-day functioning. But other side effects may be more serious and might mean that your treatment needs to be adjusted or delayed.
Be sure to know what side effects might occur with your treatment and how you should respond if they develop. Talk with your health care team about which symptoms should be reported immediately. Consider keeping notes about what side effects you experience so you can share them with your health care team during your next treatment or during any follow-up appointments.
Show Sources
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SOURCES:
Frontiers in Pharmacology: “Therapeutic evolution in HR+/HER2- breast cancer: from targeted therapy to endocrine therapy.”
National Breast Cancer Foundation: “Side Effects of Breast Cancer Treatment and How to Manage Them.”
Seminars in Oncology Nursing: “Early Recognition and Management of Side Effects Related to Systemic Anticancer Therapy for Advanced Breast Cancer.”
National Cancer Institute: “Cancer Stat Facts: Female Breast Cancer Subtypes,” “Hormone Therapy for Breast Cancer,” “Immunotherapy Side Effects”
Cleveland Clinic: “HER2-Negative Breast Cancer,” “Targeted Therapy.”
Breast Cancer Research Foundation: “Metastatic Breast Cancer: Symptoms, Treatment, Research.”
American Cancer Society: “Hormone Therapy for Breast Cancer.”
Scientific Reports: “Non-clinical evaluation of pmIL12 gene therapy for approval of the phase I clinical study.”
Mayo Clinic: “Radiation therapy for breast cancer.”
Breastcancer.org: “Jemperli: What to Expect, Side Effects, and More.”
