Treatments for HER2-Positive Breast Cancer

There are several targeted therapy options available

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Which treatment is best for your HER2-positive breast cancer depends on several factors. The stage of the cancer (whether it's early or metastatic) plays a role in this decision, as does overall hormone receptor status; some people who are HER2-positive have tumors that are also estrogen-receptor positive (triple-positive breast cancer). Options often include HER2-targeted therapies such as Herceptin (trastuzumab), Perjeta (pertuzumab), and T-DM1 (trastuzumab emtansine).

While your oncologist will consider all of this when choosing which HER2-positive treatment to recommend, it's also important to point out that receptor status can change (from positive to negative, or vice versa). The treatment plan, in turn, could change over time as well.

Around one in five or six people with breast cancer will have tumors that are HER2/neu-positive. This means that the cancerous breast cancer cells have extra activity in HER2 genes, which results in overproduction of HER2 proteins. These proteins work to drive the growth of cancer cells.

Early Stages

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

Surgery

Either a lumpectomy or mastectomy are usually recommended to remove the tumor. If the tumor is DCIS (stage 0) or if it has a favorable genetic profile, further treatments may be needed. For larger tumors, and especially those that have positive lymph nodes, adjuvant therapy is often recommended.

Hormonal Therapies

If a tumor is also estrogen receptor-positive, hormonal therapies are often recommended (following chemotherapy in those who will also have adjuvant chemotherapy).

For premenopausal women, the first choice is often tamoxifen, with aromatase inhibitors recommended for women who are postmenopausal. Alternatively, ovarian suppression therapy, ovarian ablation, or rarely, ovariectomy may be recommended for premenopausal women to reduce estrogen levels and to allow for the use of aromatase inhibitors.

It appears that aromatase inhibitors are associated with slightly higher survival rates than tamoxifen, so people who are high risk and premenopausal should discuss ovarian suppression with their doctor.

Chemotherapy

Depending on the stage of the breast cancer, the size, whether lymph node involvement is present, and gene testing, adjuvant chemotherapy may be recommended. This is usually started roughly a month after a lumpectomy or mastectomy and is done over a period of around four to six months.

HER2-Targeted Therapies

Before HER2-targeted therapies, these were considered aggressive cancers. With the advent of targeted therapy, however, this has changed and survival rates have improved.

In 1998, the first medication to directly target HER2—Herceptin (trastuzumab)—was approved. This drug is commonly used first.

Since that time, other HER2-targeted therapies have become available: Perjeta (pertuzumab) and T-DM1 (trastuzumab emtansine).

In 2017, the medication Nerlynx (neratinib) was also approved for people with early-stage HER2-positive breast cancers following treatment with Herceptin. When neratinib (a tyrosine kinase inhibitor) was added to standard therapy for breast cancer in a 2016 study, the complete response rates were higher than for 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 which have four or more positive lymph nodes, radiation therapy after mastectomy is often considered.

Tumors with one to three positive lymph nodes are in a relative gray zone, and it's important to talk with both your medical oncologist and radiation oncologist about the possible benefits of this treatment.

Bone-Modifying Drugs

Recently, the addition of bisphosphonate therapy has been considered in early-stage breast cancer, as it may reduce the risk for bone metastases in the future. Talk to your oncologist about this possibility.

Advanced Stages

With metastatic (stage 4) breast cancer, systemic therapies to control the disease are usually the goal of treatment. Surgery and radiation therapy are considered local therapies and are not often used except for palliative purposes (to reduce pain and/or prevent fractures).

A biopsy of a site of metastasis and repeating receptor studies is usually recommended to ensure that HER2 status (as well as estrogen-receptor status) have not changed.

First line therapy for advanced HER2-positive breast cancer will depend on these receptor studies. For those who are HER2-positive, one of the HER2-targeted therapies is usually used (see above).

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

The goal in treatment of metastatic breast cancer is often different than for early stage breast cancer. It involves using less treatment in order to control the disease.

If a tumor has already been treated with Herceptin (trastuzumab) in the adjuvant setting, after a treatment-free interval (measured from the end of adjuvant trastuzumab) of less than six months, the preferred second-line treatment is usually T-DM1 (ado-trastuzumab emtansine).

Alternatively, if the tumor has been already treated with Herceptin in the adjuvant setting, after a treatment-free interval of more than six months, Perjeta (pertuzumab) in combination with trastuzumab and a taxane may be used.

For patients that progress after trastuzumab and a taxane in the metastatic setting, T-DM1 is the preferred choice.

For patients that were not treated with Herceptin previously, the combination of Herceptin, Perjeta, and a taxane should be used.

Progression

If a cancer has progressed despite these treatments, a combination of Tykerb (lapatinib) and Xeloda (capecitabine) may be tried. Other chemotherapy regimens or hormonal therapies may also be tried.

Brain Metastases

HER2-positive breast cancer is more likely to spread to the brain and liver than HER2-negative tumors. Fortunately, Herceptin, and probably Perjeta, appear to pass through the blood-brain barrier and reduce the size of brain metastases.

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

Integrative Treatments

Many people ask about the possibility of alternative therapies when they are diagnosed with breast cancer. At the current time, there are no alternative therapies that have been found effective in treating breast cancer.

However, there are several integrative therapies for cancer that have been found to help people cope with the symptoms of the disease and side effects of cancer treatments, ranging from fatigue and anxiety to nausea, peripheral neuropathy, and more. Some of the therapies that have been studied specifically in women with breast cancer include yoga, meditation, massage therapy, and acupuncture.

HER2-Positive Prognosis

A 2017 study found that women with metastatic HER2-positive breast cancer had a higher survival rate than women who were HER2-negative when treatment with Herceptin was used. The lowest survival rates tend to be for women with triple-negative breast cancers.

Clinical Trials

There are many clinical trials in progress looking at different surgical, chemotherapy, and radiation therapy options, as well as comparing different hormonal and HER2-targeted therapies.

Myths about clinical trials persist, yet sometimes a clinical trial offers the best option for treatment. It's important to talk to your oncologist about any clinical trials that may be right for you.

A Word From Verywell

Herceptin changed the game when it comes to how HER2-positive cancers are treated and what people can expect when diagnosed. It and other HER2-targeted therapies can both reduce the risk of recurrence in early stage HER2-positive breast cancer and improve survival rates in metastatic HER2-positive breast cancer. Be sure you have an open discussion with your doctor about how best to treat your case and learn more about all of the options, so you are better prepared for a possible treatment change.

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