A Guide to HER2-Positive Metastatic Breast Cancer Treatments

Targeted Therapy for HER2-Positive Metastatic Breast Cancer

“HER2-targeted therapies have transformed care for this type of breast cancer,” says Arielle Medford, MD, a breast oncologist at Mass General Cancer Center affiliated with Harvard Medical School in Boston. “By targeting HER2 with any of number of therapies, we can help many patients living with this type of breast cancer live longer with well-controlled disease and lower side effects.”

• Monoclonal antibodies: Man-made immune system proteins (antibodies) that attach to the HER2 protein on cancer cells, which helps stop their growth. Examples are trastuzumab (Herceptin), pertuzumab (Perjeta), and margetuximab (Margenza).
• Antibody-drug conjugates: A monoclonal antibody connected to a chemotherapy drug (ado-trastuzumab emtansine [Kadcyla] and fam-trastuzumab deruxtecan [Enhertu]). They attach to the HER2 protein, which brings chemotherapy directly to the cancer cells.
• Kinase or small inhibitors: These drugs, including lapatinib (Tykerb), neratinib (Nerlynx), and tucatinib (Tukysa), block kinases, which are proteins within cells that relay signals telling cancer cells to grow.

Dr. Trivedi says the first-line treatment for HER2-positive breast cancer is a combination of chemotherapy with HER2-directed therapies. These medicines are given intravenously (through an IV) every three weeks for at least three cycles.

If a person responds well to treatment, Trivedi says they can often take HER2-directed therapies without the chemotherapy drug. (If the cancer is progressing, however, chemo may still be needed.)

Dr. Medford explains that because many HER2-targeted therapies are available, your doctor can switch you to a new therapy if you’re experiencing a lot of side effects.

• Blood clotting and wound healing problems
• High blood pressure
• Fatigue or tiredness
• Mouth sores
• Nail changes
• Loss of hair color
• Skin problems, such as rashes or dry skin

Chemotherapy for HER2-Positive Metastatic Breast Cancer

• capecitabine
• carboplatin
• cisplatin
• cyclophosphamide
• docetaxel
• doxorubicin
• epirubicin
• 5-fluorouracil
• gemcitabine
• ixabepilone
• doxorubicin liposomal 
• methotrexate
• paclitaxel
• vinorelbine

Chemotherapy is given intravenously in cycles, usually every 14 or 21 days. These cycles give your body enough to recover from side effects, which can include:

• Nausea
• Vomiting
• Mouth soreness
• Hair loss
• Decrease in the number of white blood cells

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Hormone Therapy for HER2-Positive Metastatic Breast Cancer

Like chemotherapy, hormone therapy may be used in combination with targeted therapy to slow the progression of HR-positive and HER2-positive metastatic breast cancer.

Hormone therapy for HR-positive and HER2-positive metastatic breast cancer may be administered with the following targeted drug therapy combinations:

• Lapatinib with letrozole
• Trastuzumab with or without pertuzumab

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Depending on which hormone therapy drug is given, you may experience some of the following side effects:

• Blood clots
• Stroke
• Bone loss
• Cataracts
• Mood swings
• Depression
• Loss of libido (sex drive)
• Joint pain
• Endometrial cancer and uterine sarcoma

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Clinical Trials for HER2-Positive Metastatic Breast Cancer

In addition to the treatments mentioned above for HER2-positive metastatic breast cancer, you may also want to consider joining a clinical trial.

“The vast therapeutic options available for patients with HER2-positive metastatic breast cancer are here thanks to clinical trials,” says Medford. “There are many promising trials underway. [People] can ask their doctors and read about available clinical trials at Clinicaltrials.gov.”

Some of the benefits of joining a clinical trial include:

• It's an opportunity to learn more about your cancer.
• It's a way to advocate for your health.
• You can assist researchers in finding new ways to prevent and treat HER2-positive cancer.
• You can help science advance, to the benefit of future generations of HER2-positive patients.

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• The responsibilities of participating in the trial (screening, medical history review, physical examinations, meeting with the research study’s team, and treatments)
• The type of healthcare you’ll receive (diagnostic tests, lab tests, X-rays, doctor’s visits, new medications, and surgical treatments)
• Whether there are any costs (meals and travel expenses) or compensation for participating in the trial

How to Manage Side Effects of HER2-Positive Metastatic Breast Cancer Treatments

If you have HER2-positive metastatic breast cancer and are undergoing treatment, here are some ways to manage side effects:

• Notify your healthcare team. Let your healthcare providers know if you’re experiencing side effects from treatment. “There are many supportive care medications that can be offered to help with some of the side effects from treatment,” says Trivedi. There are medications available that can help ease or prevent nausea, vomiting, pain, and neutropenia (low white blood cell counts), for example.

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• Consider complementary and integrative therapies. According to the National Center for Complementary and Integrative Health (NCCIH), complementary therapies, like tai chi, acupuncture, and yoga, can help relieve cancer treatment symptoms.

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  Just make sure to check in with your healthcare team before starting a new therapy, says Trivedi.
• Ask for a referral for palliative care. Palliative care is physical, emotional, and spiritual care for people living with a serious condition like metastatic breast cancer. With the help of a team that can include family members and professionals — such as palliative care specialists, social workers, nutritionists, and chaplains — palliative care can help improve your quality of life and help you better manage side effects.

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The Takeaway

Once you know your HER2 metastatic breast cancer status, you and your healthcare team will be able to find the best type of treatment for you. Treatments for HER2-positive metastatic breast cancer — which include targeted therapy, chemotherapy, and hormone therapy — can lengthen survival time and improve your quality of life.