What Is HER2-Positive Breast Cancer? Understanding Your Outlook

When you have a breast biopsy, the tissue is tested for hormone receptors (HR). It’s also tested for something called human epidermal growth factor receptor 2 (HER2). Each can be involved in the development of breast cancer.

In some pathology reports, HER2 is referred to as HER2/neu or ERBB2 (Erb-B2 receptor tyrosine kinase 2). Hormone receptors are identified as estrogen (ER) and progesterone (PR).

The HER2 gene creates HER2 proteins, or receptors. These receptors help control the growth and repair of breast cells. Overexpression of HER2 protein causes uncontrollable reproduction of breast cells.

HER2-positive breast cancers tend to be more aggressive than HER2-negative breast cancers. Along with tumor grade and cancer stage, HR status and HER2 status help determine your treatment options.

According to research published in 2019, HER2-positive breast cancer tends to affect younger women compared with HER2-negative cases. While the exact causes of HER2-positive breast cancers aren’t known, certain risk factors may contribute:

• being female
• giving birth for the first time after age 30
• being overweight
• having a sedentary lifestyle
• having a history of receiving radiation therapy in your chest area
• smoking or using other tobacco products

Also, while having a family history of breast cancer generally increases your personal risk of breast cancer development, HER2-positive breast cancer is not hereditary.

It’s not possible to self-determine whether you have HER2-positive breast cancer. If your doctor suspects cancer, further testing will reveal whether you are HER2-positive.

Overall, it’s important to see your doctor right away if you notice any of the following symptoms:

• any new or changing lumps in your breast or armpit areas
• clear, colored, or bloody nipple discharge
• unexplained pain in your breasts
• changes in your nipples or breast skin, such as dimpling, reddening, or scaliness
• nipples that turn inward
• any swelling or changes in the size or shape of your breast

Breast cancer is initially detected with the combination of:

• a physical exam
• medical history
• imaging tests such as an ultrasound or mammogram

Depending on the findings, your doctor may order a breast biopsy to test a small amount of tissue.

From there, your doctor may run a HER2 test, with the preferred method being an immunohistochemistry (IHC) test. While all breast cells have these proteins, an unusually large amount could indicate HER2-positive breast cancer. This also increases the risk of metastasis.

An IHC test result is ranked according to the following:

• 0 to 1+ IHC, indicating HER2-negative cancer
• 2+, an “equivocal” result meaning that further testing is needed
• 3+, which indicates HER2-positive breast cancer

Additionally, breast cancer is staged on a scale of 0 to IV based on:

• tumor size
• cancer cell grading
• estrogen and progesterone receptor status
• spread to lymph nodes
• spread to distant organs

While HER2-positive breast cancer is more aggressive than HER2-negative, there are now more treatment options than ever before. Your own treatment plan depends on the stage, but it will probably include a combination of therapies, such as:

• surgery
• radiation
• chemotherapy
• targeted treatments

Hormone treatments may be an option for cancer that’s also HR-positive.

Surgery

Most people who have breast cancer will have some form of surgery to help remove the tumors. Additionally, the size, location, and number of tumors help determine the need for breast-conserving surgery or mastectomy, and whether to remove the lymph nodes.

You may also consider talking with your doctor about the benefits and drawbacks of breast-conserving surgery versus a total mastectomy.

Radiation

Radiation therapy can target any cancer cells that may remain after surgery. It can also be used to shrink tumors.

This treatment measure works by radiation, such as high-energy x-rays to destroy cancer cells. Radiation therapy may be conducted either externally via a machine, or internally via catheters or needles.

Chemotherapy

Chemotherapy is a systemic treatment. Powerful drugs can seek out and destroy cancer cells anywhere in the body and can help prevent them from dividing and spreading. HER2-positive breast cancer generally responds well to chemotherapy.

Targeted treatments

Targeted treatments work to attack a specific type of cancer cell. In the case of HER2-positive breast cancer, these drugs target cells expressing the HER2 protein. They also tend to create fewer side effects than chemotherapy or radiation therapy because they don’t harm your body’s healthy (noncancerous) cells, according to the National Cancer Institute (NCI).

The targeted treatments for HER2-positive breast cancer include:

Trastuzumab (Herceptin)

Trastuzumab helps block cancer cells from receiving chemical signals that spur growth. It does this by attaching itself directly to the HER2 protein, thereby blocking incoming growth signals.

Trastuzumab was the first drug approved to specifically target the HER2 protein. It was an important step in the treatment of HER2-positive breast cancers.

Overall, according to research, using trastuzumab in combination with other treatment interventions, such as chemotherapy, is associated with:

• longer survival
• lower 1-year death rate
• longer disease-free progression, which is when the cancer is still present but doesn’t get worse
• a high response rate to treatment
• a longer response to treatment

Pertuzumab (Perjeta)

Pertuzumab is a drug that works much like trastuzumab. However, it attaches to a different part of the HER2 protein. It’s provided intravenously and is often used in combination with trastuzumab.

Ado-trastuzumab emtansine (Kadcyla)

This intravenous drug combines trastuzumab with a chemotherapy drug called emtansine. Trastuzumab delivers emtansine directly to the HER2-positive cancer cells.

It can be used to improve the survival outlook in those with metastatic breast cancer or breast cancer that’s returned. It can also be used in those with cancer that still remains (residual disease) after receiving chemotherapy and HER2-targeted therapy, before surgery.

Fam-trastuzumab deruxtecan (Enhertu)

The Food and Drug Administration (FDA) approved fam-trastuzumab deruxtecan in late 2019. Like ado-trastuzumab, this drug combines trastuzumab with a drug called deruxtecan.

Fam-trastuzumab deruxtecan is used for HER2-positive breast cancer that has spread to other areas of the body, particularly after two or more HER2-targeted therapies have already been used.

It can also be given to people with HER2-positive breast cancer that surgery can’t remove.

Neratinib (Nerlynx)

Neratinib is a year-long treatment that’s used in the early stages of HER2-positive breast cancer. It’s given to adults who’ve already completed a treatment regimen that includes trastuzumab.

The aim of neratinib is to reduce the likelihood of a recurrence.

Targeted therapies usually work from outside the cell, the chemical signals that promote tumor growth. Neratinib, on the other hand, affects chemical signals from within the cell.

Lapatinib (Tykerb)

Lapatinib blocks proteins that cause uncontrolled cell growth. It can help delay disease progression when metastatic breast cancer becomes resistant to trastuzumab.

It can be combined with oral chemotherapy or hormonal treatment to treat metastatic disease.

Tucatinib (Tukysa)

Tucatinib was FDA approved in 2020. Like neratinib and lapatinib, it also works inside the cell to block signals that lead to uncontrolled growth.

Tucatinib is used in combination with trastuzumab and capecitabine, a chemotherapy drug. It’s approved to treat HER2-positive breast cancer that’s advanced, can’t be treated using surgery, or has metastasized.

When discussing cancer treatment, it’s important to use caution when talking about whether a person’s cancer is “cured.” More often, you’ll see that the term “remission” is used.

Remission is when cancer symptoms are significantly reduced. It’s possible for remission to either be partial or complete. In a person with complete remission, all signs of cancer have disappeared.

A cancer is referred to as cured when there are no traces of cancer left in the body following treatment. If you’ve been in complete remission for 5 years or more, your doctor may say that your cancer has been cured.

However, some cancer cells can remain present in the body following treatment. Because of this, it’s possible that the cancer can return at some point. Due to this risk, your doctor may continue to monitor you for many years to make sure your cancer hasn’t returned.

Various factors, such as the cancer stage and treatment response, can influence whether a cancer goes into remission. It’s even possible for some people with metastatic HER2-positive breast cancer to experience complete remission.

Remember, every person’s situation is different.

In the United States, it’s estimated that more than 43,250 women will die from breast cancer in 2022, according to the ACS.

However, it’s important to know that aspects like life expectancy and your outlook can vary greatly based off many individual factors.

In the past, a diagnosis of HER2-positive breast cancer was associated with a poor outlook. Advances in drug therapies in recent years have improved the treatment options for HER2-positive breast cancer as well as the outlook for people with the disease.

According to the ACS, HER2-positive breast cancers are much more likely to respond to drugs that target the HER2 protein, despite the fact that they can grow and spread quickly.

Factors that affect outlook

When considering your outlook, your doctor must analyze many other factors as well. Among them are:

• Stage at diagnosis. Your outlook is better when the breast cancer hasn’t spread outside the breast or has spread only regionally at the start of treatment. Metastatic breast cancer, which is cancer that has spread to distant areas of the body, is harder to treat.
• Size and grade of primary tumor. This indicates how aggressive the cancer is.
• Lymph node involvement. Cancer can spread from the lymph nodes to distant organs and tissues.
• HR status and HER2 status. Targeted therapies can be used for HR-positive and HER2-positive breast cancers.
• Overall health. Other health issues you may have may complicate treatment.
• Response to therapy. It’s hard to predict whether a particular therapy will be effective or produce intolerable side effects.
• Age. Younger women and those over age 75 may have a worse outlook than middle-aged women, except for those with stage 3 breast cancer, according to a 2018 study.

5-year survival rates for all breast cancers

A cancer survival rate is a type of statistic that tells you what percentage of people with a diagnosis of a particular type of cancer is still alive after a certain period of time.

You’ll typically see cancer survival rates given over a 5-year period.

Currently, there’s been no specific research on survival rates for HER2-positive breast cancer alone. Current studies on breast cancer survival rates apply to all types.

According to the NCI, here are the 5-year relative survival rates for women who received a breast cancer diagnosis between 2011 and 2017:

It’s important to remember that these are overall statistics. They do not and cannot determine your personal outcome.

Also, long-term survival statistics are based on people who received a diagnosis years ago. Treatment is changing at a rapid pace and improving survival rates.

HER2-positive breast cancer is more aggressive and more likely to recur, or return, than HER2-negative breast cancer. Recurrence can happen anytime, but it usually takes place within 5 years of treatment.

The good news is that recurrence is less likely now than ever before. This is largely due to the latest targeted treatments. In fact, most people treated for early stage HER2-positive breast cancer don’t experience recurrence.

If your breast cancer is also HR-positive, hormonal therapy may help reduce the risk of recurrence.

HR status and HER2 status can change. If breast cancer recurs, the new tumor must be tested so treatment can be reevaluated.

Your loved ones can often be the first source of support when you’re living with breast cancer. It can also be helpful to reach out and connect with others (in-person or online) who may be going through some of the same experiences.

Below are a few sources to help you get started:

• Cancer Care (offers both online and in-person support groups)
• Cancer Survivors Network from the American Cancer Society
• HER 2 Positive Breast Cancer Support and Awareness Group (Facebook)
• Living Beyond Breast Cancer’s Breast Cancer Helpline
• Young Survival Coalition (online and in-person meetings)

According to the ACS, more than 3.8 million women in the United States have a history of breast cancer.

The outlook for people with HER2-positive breast cancer varies. Advancements in targeted therapies continue to improve the outlook for people with early stage or metastatic disease.

Once treatment for nonmetastatic breast cancer ends, you’ll still need periodic testing for signs of recurrence. Most treatment side effects will improve over time, but some may be permanent. You can work with your healthcare team to help manage any lasting effects.

Metastatic breast cancer isn’t considered curable. Rather, treatment relieves and manages symptoms, and can continue if it’s working. If a particular treatment stops working, you can switch to another.