Treatments for HER2-Positive Breast Cancer

If you have HER2-positive breast cancer, your options for treatment will depend on several factors, such as the stage of cancer (early or metastatic) and the hormone receptor status of the tumor.

HER2-positive tumors can also be estrogen-receptor-positive (triple-positive breast cancer). However, a tumor's receptor status can change (from positive to negative or vice versa). Therefore, the treatment plan your oncologist recommends might change as well.

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It's believed that around 20-25% of newly diagnosed cases of breast cancers are positive for a genetic mutation that causes HER2 gene amplification. The mutation causes the gene to produce too many HER2/neu proteins (or just HER2 proteins).

In normal amounts, these proteins act as receptors that tell the breast cells how much to grow (and when to stop). When the mutation is present, the overproduction of HER2 proteins drives the growth of breast cancer cells.

Therapies that specifically target HER2 include Herceptin (trastuzumab), Perjeta (pertuzumab), and T-DM1 (trastuzumab emtansine) which is sold under the brand name Kadcycla.

Early Stages

Treatment of early-stage HER2-positive breast cancer is similar to that of HER2-negative breast cancer, but it usually also includes a HER2-targeted drug such as Herceptin.

Surgery

A lumpectomy or mastectomy is typically recommended to remove the tumor in early-stage breast cancer. Radiation therapy may also be recommended either before (neoadjuvant) or after (adjuvant) surgery. Chemotherapy is not usually necessary for cancers at this stage.

If the tumor is DCIS (stage 0) or if it has a favorable genetic profile further treatment (adjuvant therapy) may not be necessary once the tumor has been removed.

Adjuvant therapy is usually recommended for large tumors and those with positive lymph nodes (stage II) as well as for tumors that are growing into surrounding tissue and spreading to lymph nodes (stage III).

Metastatic cancer (stage IV) has specific treatment protocols and does not always involve surgery.

Hormonal Therapies

If a tumor is estrogen receptor-positive, hormonal therapies are recommended. If someone is receiving chemotherapy, hormonal treatments can be started after they finish chemo.

For people who are premenopausal, tamoxifen is often the first choice. Aromatase inhibitors can be added if someone is postmenopausal. If a premenopausal person needs to take aromatase inhibitors, ovarian suppression therapy, ovarian ablation, or rarely, ovariectomy may be recommended to reduce estrogen levels.

People with early-stage breast cancer who are premenopausal and considered high-risk may want to discuss ovarian suppression with their healthcare provider. Research suggests that in some cases, aromatase inhibitors are associated with slightly higher survival rates than tamoxifen.

Chemotherapy

Depending on the cancer stage, tumor size, lymph node involvement, and results of genetic testing, adjuvant chemotherapy may be recommended. Treatment typically begins one month after a lumpectomy or mastectomy and continues for around four to six months.

HER2-Targeted Therapies

Before HER2-targeted therapies, HER2 tumors were considered aggressive cancers. With the advent of targeted therapy, survival rates have improved.

In 1998, Herceptin (trastuzumab), the first medication to directly target HER2, was approved by the FDA. Oncologists usually start with this drug before trying other treatments.

In the decade following its advent, Herceptin was joined by two more HER2-targeted therapies: Perjeta (pertuzumab) and T-DM1 (trastuzumab emtansine).

In 2017, Nerlynx (neratinib) was also approved for people with early-stage HER2-positive breast cancers following treatment with Herceptin.

In 2019 the FDA approved Enhertu (fam-trastuzumab-deruxtecan-nxki) to treat adults with certain types of HER2-positive breast cancer. In 2022, the FDA expanded the use of Enhertu to treat HER2-positive and HER2-low breast cancers that have come back during or within six months of completing treatment for early-stage breast cancer.

According to a 2016 study, when neratinib (a tyrosine kinase inhibitor) was added to standard therapy for breast cancer, complete response rates were higher than they were in people treated with Herceptin plus standard therapy.

Tykerb (lapatinib) is another tyrosine kinase inhibitor that may be used after treatment with Herceptin or other HER2 therapies.

Radiation Therapy

For people who choose a lumpectomy, radiation therapy is usually recommended following surgery. For tumors that have four or more positive lymph nodes, radiation therapy after a mastectomy is often considered.

Tumors with one to three positive lymph nodes are in a relative gray zone. In this case, you'll want to talk with both your medical and radiation oncologist about the possible benefits of the treatment.

Bone-Modifying Drugs

The addition of bisphosphonate therapy has been considered in early-stage breast cancer, as it may reduce the risk for bone metastases.

Advanced Stages

With metastatic breast cancer, systemic therapies to control the disease are usually the goal of treatment. Surgery and radiation therapy are considered local therapies and are mainly used only for palliative purposes (to reduce pain and/or prevent fractures).

A biopsy of a metastasis site and repeated receptor studies are recommended to ensure that HER2 status and estrogen-receptor status have not changed.

First-line therapy for advanced HER2-positive breast cancer depends on the results of receptor studies. For people who are HER2-positive, one of the HER2-targeted therapies outlined above is usually used.

If a tumor is also estrogen-receptor-positive, hormonal therapy, HER2 therapy, or both may be considered. Chemotherapy may also be used for several months.

If a tumor has already been treated with Herceptin (trastuzumab) as adjuvant therapy and the disease comes back within six months of ending treatment with adjuvant trastuzumab, the preferred second-line treatment is usually T-DM1.

For someone with early-stage breast cancer who has already received Herceptin in the adjuvant setting but is considered to be at high risk for recurrence, Perjeta (pertuzumab) in combination with trastuzumab and a taxane may be used.

For cancer that progresses after trastuzumab and a taxane in the metastatic setting, T-DM1 is the preferred choice. If a person was not previously treated with Herceptin, the combination of Herceptin, Perjeta, and a taxane may be used.

If a tumor has already been treated with HER2-based therapy and the disease comes back within six months of ending treatment, or the tumor cannot be removed by surgery or has spread to other parts of the body, Enhertu may be used.

Progression

If cancer progresses despite these treatments, a combination of Tykerb (lapatinib) and Xeloda (capecitabine), as well as other chemotherapy regimens or hormonal therapies, can be tried.

Brain Metastases

HER2-positive breast cancer is more likely to spread to the brain and liver than HER2-negative tumors. It appears that Herceptin (and possibly Perjeta) can pass the blood-brain barrier and reduce the size of brain metastases.

For people with bone metastases, bone-modifying drugs such as bisphosphonates can not only reduce the risk of fractures but may improve survival as well.

Integrative Treatments

Many people ask about alternative therapies when they are diagnosed with breast cancer. There are no proven "natural cures" for breast cancer and no alternative therapies have been found to effectively treat the disease.

However, there are several integrative therapies for cancer that may help people cope with the symptoms of the disease and the side effects of cancer treatments (such as fatigue, anxiety, nausea, peripheral neuropathy, and more).

Some integrative therapies that have been studied specifically in women with breast cancer include yoga, meditation, massage therapy, and acupuncture.

A 2017 study found that women with metastatic breast cancer who were HER2-positive responded to Herceptin more favorably than women who were HER2-negative and were not eligible for the treatment.

Clinical Trials

There are clinical trials exploring surgical, chemotherapy, and radiation therapy options for breast cancer, as well as studies comparing different hormonal and HER2-targeted therapies.

Myths about clinical trials persist, yet they can sometimes offer the best option for treatment. Your oncologist can explain how clinical trials work and let you know if there are any that would be right for you.

A Word From Verywell

Herceptin forever changed how HER2-positive cancers are treated and what people can expect when they are diagnosed. Herceptin and other HER2-targeted therapies have been shown to both reduce the risk of recurrence in early-stage HER2-positive breast cancer and improve survival rates in metastatic HER2-positive breast cancer.

The treatment your healthcare provider recommends will depend on different factors, such as your cancer's stage; the size and spread of tumors; and whether you have already tried other treatments. Your oncologist will explain the available options and help you decide which treatment is right for you.