HER2-Negative Breast Cancer

HER2-negative breast cancer is the most common type of breast cancer, affecting about 4 out of 5 people diagnosed with the disease. Understanding your HER2 status helps your healthcare team choose the right treatment plan for you.

Table of contents

• What Is HER2-Negative Breast Cancer?
• Types of HER2-Negative Breast Cancer
• Symptoms
• Causes and Risk Factors
• Diagnosis
• Treatment Options
• Outlook and Prognosis

What Is HER2-Negative Breast Cancer?

HER2-negative breast cancer involves having cancerous cells in your breast that don’t contain high levels of the protein human epidermal growth factor receptor 2 (HER2)^[1]. HER2 is a protein found on the surface of all breast cells that helps control their growth and repair. In healthy cells, this protein ensures that cells divide normally to replace those that are damaged or dying^[6].

When cancer cells make too much HER2 protein, the cancer is more likely to multiply and grow aggressively. This is called HER2-positive breast cancer. If your doctor says your breast cancer is HER2-negative, it means your cancer isn’t making a lot of extra HER2^[2].

Healthcare providers classify HER2-negative breast cancers based on what doesn’t fuel cancer growth — excess HER2. Instead, other factors cause tumors to form. Your healthcare provider will determine your HER2 status as part of your diagnosis. Understanding the characteristics of cancer cells, or biomarkers, helps providers determine which treatments will work best^[1].

Types of HER2-Negative Breast Cancer

Most breast cancer diagnoses are HER2-negative. About 4 out of 5 breast cancers don’t have extra HER2^[2]. There are two main types based on the tumor’s hormone receptor status.

HR-positive and HER2-negative breast cancer (HR+/HER2-): This type accounts for about 70% of all breast cancers. It involves cancer cells that do have hormone receptors for estrogen (ER+), progesterone (PR+), or both. The hormones fuel tumor growth, but these cancers don’t have high levels of HER2^[1][2].

HR-negative and HER2-negative breast cancer (HR-/HER2-): This type accounts for about 11% of all breast cancers. It involves cancer cells that don’t have hormone receptors for estrogen or progesterone. They also don’t have high levels of HER2. Neither hormones nor HER2 fuel tumor growth. Another name for this type is triple-negative breast cancer^[1][2].

Understanding your HER2 status together with your hormone receptor status tells you and your doctors about the biology of the cancer. It helps doctors decide which treatment is best to try first and what options you have if you need to try something else later^[2].

Symptoms

The symptoms of HER2-negative breast cancer are the same as with breast cancer in general. HER2-negative and HER2-positive breast cancers have the same symptoms. Your doctor can’t tell which type you have by examining you^[2].

Signs to look out for include:

• Changes in your breast’s size or shape
• A new lump or hardened area in or near your breast or armpit that doesn’t change in response to your periods
• Skin changes affecting your breast or nipple, including dimpled, puckered, scaly, itchy, or discolored (reddish, purple, or unusually dark) skin
• Nipple discharge, including bloody or clear fluid
• A nipple that pulls inward^[1]

It’s important to remember that breast cancer doesn’t always cause changes you can see. Also, many of these changes are common in noncancerous conditions. This is why it’s important to get regular breast cancer screenings. See a healthcare provider if you’re unsure if changes are signs of cancer or a benign condition^[1].

Causes and Risk Factors

HER2-negative breast cancer forms when the DNA in breast cells changes (mutates) and becomes cancer cells. The cells divide uncontrollably and form tumors^[1].

Experts don’t know what causes the mutations that lead to tumors in HER2-negative breast cancer. But they’ve identified several factors that may increase your breast cancer risk. These include:

• Inherited genetic mutations: There isn’t a mutation that causes HER2-related breast cancers specifically. But inheriting the BRCA1 or BRCA2 gene mutations increases your overall breast cancer risk^[1].
• A personal or family history of breast cancer: A previous breast cancer diagnosis increases your risk. So does having biological relatives with breast cancer (especially a parent, sibling, or child)^[1].
• Long-term exposure to high levels of estrogen or progesterone: Getting your first period at an early age or starting menopause late increases your lifetime exposure to sex hormones. Some forms of hormone therapy can increase your risk^[1].

Diagnosis

Your doctor will run a test on a small piece of your tumor to determine your HER2 status. They’ll get the sample for testing either during a biopsy or in surgery^[2].

Your HER2 status is one of many things that affect how fast your breast cancer will grow. There are other hormone receptors that respond to hormones in your blood as well. Doctors also sometimes refer to receptors separately as estrogen receptors (ER) and progesterone receptors (PR)^[2].

Doctors often talk about all the different receptors together. So your HER2-negative cancer will be either HR-positive/HER2-negative or HR-negative/HER2-negative. If your cancer is negative for HER2 and both types of hormone receptors, it’s called triple negative^[2].

Knowing your breast cancer’s HER2 status — together with its hormone receptor status — tells you and your doctors about the biology of the cancer. It helps doctors decide which treatment is best to try first and what options you have if you need to try something else later. Doctors might also look at other factors, including genetic or other changes in your cancer that could affect how fast it’s likely to grow or spread^[2].

Treatment Options

Some breast cancer treatments work by targeting HER2. If your cancer is HER2-negative, your doctor won’t use those therapies. They’ll suggest other options based on how advanced your cancer is and whether it’s positive for hormone receptors^[2].

Treatment options for HER2-negative breast cancer include surgery, radiation therapy, chemotherapy, hormone therapy, immunotherapy, and certain types of targeted therapy^[4].

Hormone Therapy

Hormone therapy is often the first treatment doctors use for women with HER2-negative breast cancer that’s hormone receptor positive. Some 67% to 80% of breast cancers are hormone receptor positive. That means your hormones, like estrogen or progesterone, help the cancer grow^[11].

Hormonal or endocrine therapies help to block this process. Some drugs lower your levels of estrogen. Others stop estrogen from connecting to cancer cells so they can’t multiply. Hormonal therapies have a lower risk of serious side effects than chemotherapy. So you may have a better quality of life during treatment^[11].

Hormonal therapies include:

• Aromatase inhibitors (AIs) like anastrozole (Arimidex), exemestane (Aromasin), and letrozole (Femara)
• Fulvestrant (Faslodex)
• Tamoxifen (Nolvadex, Soltamox)
• Toremifene (Fareston)
• Drugs that stop your body from making estrogen, like goserelin (Zoladex) and leuprolide (Lupron)^[11]

Chemotherapy

Chemotherapy or “chemo” is medicine that kills cancer cells. You can take it as pills or get it through an IV. Many different chemotherapy drugs are used, either alone or in combination, to treat HER2-negative breast cancer. Your doctor will prescribe a chemo drug based on your past treatments, your preferences, any other conditions you have, and your risk of side effects^[11].

Targeted Therapies

Targeted therapies block certain proteins or molecules that drive the growth and spread of cancer cells. Those molecules are the “targets” of the drugs. These drugs are also called precision medicine. Your doctor prescribes a certain drug based on your genes or the proteins associated with your specific cancer^[11].

Targeted therapies for HER2-negative breast cancer include:

• PARP inhibitors like olaparib (Lynparza) and talazoparib (Talzenna). These drugs stop a protein known as poly-ADP ribose polymerase (PARP) from repairing cancer cells, so the cells die. They’re given to women who have a mutation in the BRCA gene and HER2-negative breast cancer^[11].
• Other targeted therapies may be used depending on specific characteristics of your cancer^[11].

Immunotherapy

Immunotherapy is another treatment option that may be used for some types of HER2-negative breast cancer. This approach helps your immune system fight cancer cells^[11].

Surgery and Radiation

Surgery and radiation therapy are also important treatment options for HER2-negative breast cancer, depending on the stage and location of the cancer^[4].

Outlook and Prognosis

Breast cancer that’s HER2-negative tends to have a better outlook than those that are HER2-positive, since HER2-negative makes the cancer less aggressive^[2].

However, your outlook can vary depending on a variety of factors, including the stage of cancer at diagnosis, whether it’s hormone receptor positive or negative, your age, and your overall health. Cancers can change over time, so ongoing monitoring is important^[2].

When you have HER2-negative breast cancer, treatment usually focuses on managing your disease and helping you live longer with a better quality of life. The goal of treatment depends on whether the cancer is early stage or has spread to other parts of the body^[11].