Treatments for HER2 Positive Breast Cancer

There are multiple targeted therapy options available

woman in cancer therapy contemplating decisions
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In the last few decades, we've learned that not all breast cancers are alike. In addition to variations that can be seen under the microscope, there are differences between these cancers on a molecular level. After you have a biopsy or surgery you will learn about whether your breast cancer is estrogen receptor positive or progesterone receptor positive, as well as your HER2 status.

If you have been told that your breast cancer is HER2 positive, what does that mean?

What treatments work specifically for this type of breast cancer and what other treatments may be used?

Overview of Treatment Options

People who have HER2-positive breast cancers may be treated in a way similar to people with HER2 negative tumors in some ways. For example, surgery (either a lumpectomy or mastectomy,) adjuvant chemotherapy, and/or hormonal therapy (if the tumor is estrogen receptor positive) may be used.

Targeted therapies specific for HER2 positive tumors are also used and have improved survival rates for HER2-positive tumors. The treatment options for both early stage and metastatic disease are discussed below.

How Targeted Therapies Work

Around one in five or six people with breast cancer will have tumors which 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 the cancer cell.

HER2 positive breast cancers tend to be more aggressive, and in earlier years had a poorer prognosis. In 1998 the first medication to directly target HER2 was approved. This medication is Herceptin (trastuzumab).

Since that time other HER2 targeted therapies have been found. Perjeta (pertuzumab) and T-DM1 (trastuzumab emtansine) have also been approved.

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.

Treatments for 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.

Options include:

  • 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 (gene testing to detect the risk of recurrence), further treatments may be needed. For tumors which are larger, and especially those which 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.
  • 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: As noted above, there are now several options for targeted treatment of HER2-positive breast tumors, including Herceptin (trastuzumab), Perjeta (pertuzumab), and T-DM1 (trastuzumab emtansine), with other drugs being evaluated in clinical trials. Most commonly, Herceptin is used first. Tykerb (lapatinib) is a tyrosine kinase inhibitor effective for HER2 positive tumors. Nelynx (neratinib), another kinase inhibitor, was also recently approved for the treatment of early-stage HER2-positive breast cancer following treatment with Herceptin.
  • 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.
  • 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. There are many myths about clinical trials, yet sometimes a clinical trial offers the best option for treatment. It's important to talk to your oncologist about any clinical trials which may be right for you.
  • 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.

Treatments for 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).

If metastatic HER2-positive breast cancer is a distant breast cancer recurrence of an early stage breast cancer, it's important to note that the HER2 status (as well as estrogen receptor status) can change. A biopsy of a site of metastasis and repeating receptor studies is usually recommended. A tumor which was initially HER2 positive may be HER2 negative upon recurrence and vice versa.

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. 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.

It's important to note that the goal in the treatment of metastatic breast cancer is often different than that for early stage breast cancer, in that as little treatment as possible in order to control the disease is usually recommended.

If a tumor has already been treated with Herceptin, the preferred second line treatment is usually T-DM1 (trastuzumab emtansine). Alternatively, Perjeta (pertuzumab) may be used. If T-DM1 has been used, Herceptin plus Perjecta may be used. Finally, the newly approved in 2017 drug Nerlynx (neratinib) may be used after Herceptin.

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.

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 not any "alternative" therapies which have been found effective in treating breast cancer. Instead, some people who have chosen these therapies to the exclusion of conventional treatments have lost out on therapies that have been shown to be effective.

But it's important not to throw the baby out with the bathwater. There are several integrative therapies for cancer that have been found to help people cope with the symptoms of the disease and 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.

Prognosis

Before HER2 targeted therapies, there was no specific treatment available for HER2 positive tumors, and these were considered aggressive cancers. With the advent of targeted therapy, however, this has changed.

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.

Finding Support

Fortunately, increased awareness and funding for breast cancer has given rise to a multitude of resources to help people cope with the disease. Support groups and support communities are available for women with breast cancer in general, as well as for those who are specifically coping with metastatic cancer. Online communities and even Facebook groups of people with HER2-positive breast cancer have gathered together as they face their unique challenges.

Participating in social media has been a source of both support and education for many people with the disease. If you choose to become involved in this way, however, take a moment to learn how to share your cancer journey online safely.

The internet is a big place and it can sometimes be difficult finding people who are facing a similar journey to yours. In order to connect with others who are living with, or treating, breast cancer, using the hashtag #BCSM is very helpful. BCSM stands for breast cancer social media.

A Word From Verywell

In the past, HER2-positive breast cancer was considered an aggressive tumor without any specific treatment available. That all changed in 1998 with the approval of the first HER2 targeted therapy, Herceptin. Since that time, other medications have become available including Perjeta, T-DM1, lapatinib, and most recently neratinib, with other drugs being evaluated in clinical trials. 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.

In addition to HER2 targeted therapies, the treatment of HER2-positive breast cancers also includes the treatments for HER2 negative disease such as surgery, hormonal therapy (when applicable), chemotherapy, radiation therapy, specific treatments for metastases, and the possibility of clinical trials.

Sources:

Chan, A., Delaloge, S., Holmes, F. et al. Neratinib After Trastuzumab-Based Adjuvant Therapy in Patients with HER2-Positive Breast Cancer (ExteNET): A Multicentre, Randomised, Double-Blind, Placebo-Controlled Phase 3 Trial. Lancet Oncology. 17(3):367-77.

Kast, K., Schoffer, O., Link, T. et al. Trastuzumab and Survival of Patients With Metastatic Breast Cancer. Archives of Gynecology and Obstetrics. 2017. 296(2):303-312.

Park, J., Liu, M., Yee, D. et al. Adaptive Randomization of Neratinib in Early Breast Cancer. The New England Journal of Medicine. 2016. 375(1):11-22.

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