HER2-Positive Breast Cancer Treatment

HER2-positive breast cancer is characterized by an overproduction of the human epidermal growth factor receptor 2 (HER2) protein, which normally regulates cell growth. When produced in excess, however, HER2 can cause the cells to divide and grow uncontrollably, leading to tumor development.

Scientists believe HER2 overexpression results from cellular mutations in the HER2 gene. In most cases, these genetic changes occur spontaneously and are not inherited. The precise cause is unknown.

The symptoms of HER2-positive breast cancer can be similar to those of other types of breast cancer. Common signs include a lump in the breast or armpit, unusual nipple discharge, changes in breast shape, breast swelling and skin dimpling.

According to the American Cancer Society, HER2-positive breast cancer accounts for approximately 15 to 20% of all breast cancer cases. While it tends to grow and spread more rapidly than other types, it often responds well to HER2-targeted therapy, which is designed to block the activity of the HER2 protein and has no effect on HER2-negative breast cancer.

How is HER2 status determined?

Typically, the diagnostic process for HER2-positive breast cancer involves an imaging test, such as a mammogram or breast ultrasound, followed by a biopsy to confirm the presence of cancerous cells. The biopsy sample will also be tested to determine the HER2 status of the tumor. The goal is to find out whether the cancer cells have excessive levels of the HER2 protein or extra copies of the HER2 gene. In either case, the tumor may respond to HER2-targeted therapy. The two main laboratory tests used for this purpose are:

Immunohistochemistry (IHC)

IHC measures the amount of HER2 protein on the surface of cells. The results are reported on a scale from 0 to 3+:

• 0 or 1+ – HER2-negative (no HER2 overexpression)
• 2+ – Borderline or equivocal (further testing required)
• 3+ – HER2-positive (HER2 overexpression confirmed)

Additionally, a diagnosis of HER2-low breast cancer may be confirmed if the tumor tests positive for the HER2 protein at a level lower than 3. Newly defined by the U.S. Food & Drug Administration (FDA), this subset of HER2-positive breast cancer may respond to certain HER2-targeted therapies, such as Enhertu®.

Fluorescence in situ hybridization (FISH)

FISH uses fluorescent markers to check for extra copies of the HER2 gene in the cancer cells. More precise than immunohistochemistry, FISH is often used to follow up on a borderline IHC result. A positive FISH test indicates HER2 gene amplification.

Targeted therapy for HER2-positive breast cancer

Targeted therapy uses specialized medications to destroy cancer cells or slow their growth. For example, HER2-targeted therapy uses drugs that target the HER2 protein, which normally helps the cancer cells grow and spread. These drugs may be administered through intravenous (IV) infusion or injection or taken orally in pill form.

In the past, patients with HER2-low breast cancer had limited options for targeted therapy. However, recent clinical trials have paved the way for those with HER2-low breast cancer to receive targeted therapy.

Enhertu® – A new treatment option for HER2-positive breast cancer

Enhertu is the brand name for fam-trastuzumab deruxtecan-nxki, a chemotherapy drug that combines trastuzumab, a HER2 monoclonal antibody, with deruxtecan, an agent that can slow or prevent cell replication. This targeted drug is approved by the FDA for the treatment of certain types of HER2-positive and HER2-low breast cancer.

Moffitt Cancer Center took part in a landmark clinical trial that led to the FDA approval of Enhertu as a treatment for certain patients with HER2-low breast cancer. This groundbreaking study evaluated Enhertu in comparison to conventional chemotherapy, the existing standard of care for HER2-positive breast cancer. The results showed that Enhertu can significantly delay disease progression in a patient with an aggressive form of metastatic breast cancer.

Enhertu, an antibody-drug-conjugate, is a new way to get therapy into cells to reduce the risk of systemic side effects typically seen when the drug is given directly. We are in the infancy of what these drugs can do, but the future is bright.

Monica Avila, MD

Chemotherapy for HER2-positive breast cancer

In addition to HER2-targeted therapy drugs, several standard chemotherapy agents may be used to treat HER2-positive breast cancer. These include:

• Taxanes, such as paclitaxel (Taxol®) and docetaxel (Taxotere®)
• Anthracyclines, such as doxorubicin (Adriamycin®) and epirubicin (Ellence®)
• Alkylating agents, such as cyclophosphamide (Cytoxan®)
• Antimetabolites, such as capecitabine (Xeloda®) and 5-Fluorouracil (5-FU)
• Platinum-based drugs, such as carboplatin and cisplatin

Traditional chemotherapy medications do not specifically target the HER2 protein. Instead, these powerful drugs work by destroying rapidly dividing cells throughout the body, which can help reduce or eliminate cancer.

Frequently asked questions (FAQs) about HER2-positive breast cancer treatment

Ongoing advances in targeted therapy and other treatments continue to improve outcomes and quality of life for patients with HER2-positive breast cancer, which tends to be aggressive. Some FAQs about treatment include:

What is the primary treatment approach for HER2-positive breast cancer?

For early-stage HER2-positive breast cancer, treatment often begins with a combination of HER2-targeted therapy and chemotherapy, which can shrink the tumor and make it easier to remove. Depending on the type and stage of the cancer and the patient’s preferences, the next step may be a lumpectomy or mastectomy to remove the tumor along with some surrounding tissues. In many cases, surgery is followed by radiation therapy to target any remaining cancer cells and help prevent recurrence.

For advanced or metastatic breast cancer, ongoing HER2-targeted therapy can help control the tumor and maintain quality of life.

What is HER2-targeted therapy, and how does it work?

HER2-targeted therapy is a breast cancer treatment designed to block the HER2 protein, preventing it from sending signals that promote tumor cell growth. These medications can be highly effective with minimal side effects, mainly because they specifically target cancer cells while sparing healthy cells.

HER2-targeted drugs include:

• Trastuzumab (Herceptin®)
• Pertuzumab (Perjeta®)
• Ado-trastuzumab emtansine (Kadcyla®)
• Trastuzumab deruxtecan (Enhertu®)

Depending on the type and hormone receptor status of the tumor, targeted therapy may be used in combination with chemotherapy or hormone therapy for heightened treatment effectiveness.

Besides targeted therapy, what other treatments can be used for HER2-positive breast cancer?

In addition to targeted therapy, treatment for HER2-positive breast cancer may include:

• Chemotherapy – Powerful medications enter the bloodstream and circulate throughout the body to target and destroy rapidly dividing cells.
• Surgery – A surgical procedure, such as a lumpectomy or mastectomy, may be considered based on the location and size of the tumor and the patient’s preferences.
• Radiation therapy – Often administered after surgical treatment for breast cancer, radiation therapy can help eliminate any remaining cancer cells and reduce the risk of recurrence.
• Hormone therapy – For cancers that are both HER2-positive and hormone receptor-positive, hormone-blocking medications may also be prescribed.

The oncologist will develop a personalized treatment plan based on the stage of the tumor and the patient’s overall health and treatment goals.

Are there clinical trials available for new HER2-targeted therapies?

Yes. Clinical trials play a vital role in advancing the treatment for HER2-positive breast cancer. Through ongoing research studies, scientists are continually evaluating novel targeted therapies, immunotherapies and combinations of existing treatments to improve outcomes and reduce side effects.

Patients interested in clinical trials are encouraged to talk with their oncologist about the available options. In addition to gaining early access to cutting-edge treatment options, a clinical trial participant can contribute to future breakthroughs in breast cancer care.

What are the side effects of HER2-positive breast cancer treatment?

HER2-positive breast cancer treatment may involve a combination of targeted therapy, chemotherapy, radiation therapy and sometimes hormone therapy. While effective, these therapies may cause side effects that can vary based on the specific drugs used and the patient’s individual response.

Possible side effects of HER2-targeted therapy

HER2-targeted drugs are designed to specifically attack cancer cells that overproduce the HER2 protein. However, healthy cells are sometimes affected as well, which may lead to side effects. Some patients experience:

• Fatigue
• Nausea
• Diarrhea
• Headache
• Low blood cell counts
• Mild infusion-related reactions, such as fever and chills

A less common but potentially serious side effect of targeted therapy is heart damage (cardiotoxicity), which can weaken the heart muscle and affect its ability to pump blood. During treatment, the healthcare team will continually monitor the patient’s heart function and check for early signs of cardiotoxicity.

Possible side effects of chemotherapy for HER2-positive breast cancer

Chemotherapy targets and destroys rapidly dividing cells throughout the body. Along with cancer cells, it can also impact healthy cells that renew themselves frequently, including those in the hair roots, blood-forming tissues, skin and lining of the mouth and intestines. The side effects can vary based on the drug combination used, but often include:

• Hair thinning or hair loss
• Nausea and vomiting
• Fatigue and weakness
• Loss of appetite
• Unintended weight loss
• Mouth sores
• Increased risk of infection due to low white blood cell counts
• Numbness or tingling sensations in the hands and feet (neuropathy)

Although most side effects of chemotherapy are temporary and improve after treatment ends, some may linger, such as fatigue and neuropathy.

Possible side effects of radiation therapy for HER2-positive breast cancer

Radiation treatment can potentially cause fatigue, weakness and localized side effects, such as:

• Skin irritation or redness in the treated area
• Breast swelling or tenderness

Usually, these side effects develop gradually and resolve over time.

Possible side effects of hormone therapy for HER2-positive breast cancer

For a patient with HER2-positive cancer that is also hormone receptor-positive, hormone-blocking medications may be incorporated into the treatment plan. Possible side effects of hormone therapy include:

• Hot flashes
• Night sweats
• Mood swings
• Joint pain or stiffness
• Vaginal dryness

Managing the side effects of HER2-positive breast cancer treatment

Throughout treatment, the healthcare team will closely monitor the patient to help manage any side effects and adjust the treatment plan if needed. Supportive medications, nutrition counseling and integrative therapies can often reduce discomfort and help maintain quality of life.

Can treatment cure HER2-positive breast cancer?

In many cases, HER2-positive breast cancer can be treated successfully, especially when diagnosed early. Recent advances in targeted therapy have dramatically improved long-term outcomes, reduced recurrence rates and enhanced the quality of life for many patients. As research continues, more progress is being made every day. That said, the outlook in each case can vary depending on several factors, including the stage of the tumor, the patient’s overall health and how the cancer responds to treatment.

In cases of advanced or metastatic HER2-positive breast cancer, treatment may not completely eliminate the tumor. However, it can often control the cancer for an extended period, allowing the patient to maintain a good quality of life.

Benefit from world-class care at Moffitt Cancer Center

At Moffitt, we take an individualized approach to HER2-positive breast cancer treatment. The multispecialty team in our renowned Don & Erika Wallace Comprehensive Breast Program focuses exclusively on breast cancer and collaborates to ensure each patient receives a treatment plan tailored to their unique needs. For these reasons and others, we consistently achieve outcomes that exceed national averages, and our patients maintain the best possible quality of life.

Moffitt has also been designated as a Comprehensive Cancer Center by the National Cancer Institute, an achievement that speaks directly to our dedication to advancing cancer care for all current and future patients. Through our robust clinical trials program, our patients can be among the first to benefit from the latest breakthroughs in treatment before those options are made available elsewhere.

If you would like to learn more about HER2-positive breast cancer treatment, you can request an appointment with a specialist at Moffitt by calling 1-888-663-3488 or submitting a new patient registration form online. We do not require referrals.

References

American Cancer Society – Targeted Drug Therapy for Breast Cancer
American Cancer Society – Enhertu May Be Preferred Therapy for Some Metastatic Breast Cancers