HER2-Negative Breast Cancer

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 2 (HER2). With most breast cancers, hormones and/or the HER2 protein fuel cancer growth. For example, with HER2-positive breast cancer, excess HER2 leads to cancerous tumors.

Experts 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 HER2 status as part of your diagnosis. Understanding the characteristics of cancer cells, or “biomarkers,” helps providers determine which treatments will work best.

Types of HER2-negative breast cancer

Most breast cancer diagnoses are HER2-negative. There are two main types:

• HR-positive and HER2-negative breast cancer (HR+/HER2-). This type accounts for 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.
• HR-negative and HER2-negative breast cancer (HR-/HER2-). This type accounts for 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.

What are the symptoms of HER2-negative breast cancer?

The symptoms of HER2-negative breast cancer are the same as with breast cancer in general. 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

It’s important to remember that breast cancer doesn’t always cause changes you can see. Also, many of these changes are common in benign (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.

What causes HER2-negative breast cancer?

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

Risk factors

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.
• 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).
• 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, too.
• Alcohol use. Having more than one alcoholic beverage a day can increase your risk.

How is HER2-negative breast cancer diagnosed?

Healthcare providers diagnose HER2-negative breast cancers with a breast biopsy. Your provider will remove a sample of the tumor and send it to a lab for testing. If results show cancer cells, a pathologist will perform tests to check for the HER2 protein. A normal amount of HER2 genes or proteins means you have HER2-negative breast cancer.

Lab tests include:

• Immunohistochemistry (IHC). This test uses antibodies to detect the HER2 protein on cancer cells. If IHC results are 0 or 1+ on lab test results, the cancer is HER2-negative. If results are 2+, you’ll need a FISH test to confirm the HER2 status.
• Fluorescence in situ hybridization (FISH). This test uses a special microscope to detect the HER2 gene that makes the HER2 protein. Providers use it to confirm the results of IHC.

The pathologist will run tests on the biopsy sample to learn if the cancer has hormone receptors for estrogen or progesterone. You’ll also need imaging procedures so your provider can stage your cancer. Staging allows them to see how big the tumor is and if it’s spread.

Taken together, this information helps your provider plan treatment.

What are the treatments for HER2-negative breast cancer?

The best treatments for HER2-negative breast cancer depend on many things. This includes cancer stage and whether the cancer has hormone receptors.

Depending on these factors, treatment may include breast cancer surgery to remove the tumor. You may need treatments before surgery or after. For example, you may need radiation therapy after surgery to destroy any remaining cancer cells.

HR+/HER2- breast cancer

In addition to surgery and/or radiation, treatments for HR+/HER2- breast cancer include:

• Hormone therapy. These treatments reduce the hormones that fuel cancer growth. Examples include drugs like aromatase inhibitors, Gonadotropin-releasing hormone (GnRH) agonists or selective estrogen receptor modulators (SERMs). In select cases, you may need surgery to remove your ovaries, which make estrogen. You may need hormone therapies alone or in combination with targeted therapy.
• Targeted therapy. These treatments hone in on weaknesses in cancer cells to keep them from making more cells. CKD4/6 inhibitors are just one example. This treatment blocks an enzyme that fuels cancer growth.
• Chemotherapy. Providers sometimes prescribe chemotherapy in addition to hormone therapy with or without targeted therapy for HR+/HER2- and HER2- breast cancers.

HR-/HER2- breast cancer

Hormone therapy isn’t an effective treatment for triple-negative breast cancers. In addition to surgery and/or radiation, treatment may involve:

• Chemotherapy. Providers use different types of chemotherapy drugs to treat breast cancer. You may need a single drug or a combination of chemotherapy drugs. For HR- and HER2-negative breast cancers, providers sometimes recommend chemotherapy alongside immunotherapy.
• Immunotherapy. This treatment makes your immune system more effective at fighting cancer cells. Pembrolizumab (Keytruda®) is an example of a Food and Drug Administration (FDA)-approved immunotherapy drug your provider may prescribe if you have triple-negative breast cancer.
• Targeted therapy. Depending on the genetic mutations in the cancer cells, your provider may recommend taking drugs called PARP inhibitors in addition to chemotherapy and immunotherapy. There are also new types of targeted therapies for metastatic disease.

What are the side effects of the treatment?

Treatments effectively fight cancer, but common cancer treatments — like chemotherapy, radiation and immunotherapy — have side effects that you should know about. Ask your healthcare provider about what to expect. They can also connect you with palliative care resources. Palliative care can help you manage symptoms no matter your cancer type or stage.

What is the survival rate of HER2-negative breast cancer?

With all HER2- breast cancers, local cancers (those that haven’t spread) have better survival rates than metastatic cancer (cancer that spreads to distant organs). Survival rates for regional cancers (cancers that have spread to nearby tissue but not distant organs) are in between.

It’s important to remember, though, that your prognosis depends on your unique diagnosis. This includes information about cancer spread and hormone status. But your health and response to treatment also play a role. These are things your healthcare provider can discuss with you so you know what to expect.

How do I take care of myself?

It’s important to take time for self-care, whether you’re living with early-stage or advanced HER2-negative breast cancer. Here are some things you can do:

• Rest when you need to. It’s normal for both cancer and cancer treatments to make you feel exhausted. Allow yourself time to stop and rest when you’re tired.
• Eat well. Some cancer treatments can affect your appetite. Make sure you’re getting the nutrition you need. Talk to a dietitian if you need guidance about what foods to eat.
• Exercise (but don’t overdo it). Regular exercise is important, but the amount you need and the intensity depend on your diagnosis. Ask your healthcare provider about what your fitness goals should be.
• Manage stress. Managing stress is different for different people. While meditation may work for some people, others may prefer being active (light walks, starting a creative project). Make time for whatever activities work to keep you feeling calm.
• Seek emotional support. Connecting with others who are managing a cancer diagnosis is just as important as leaning on family and friends for support. Ask your healthcare provider about cancer survivorship programs that allow you to connect with others.

When should I see my healthcare provider?

Contact your healthcare provider if you notice new symptoms or if your current symptoms seem to be getting worse.

Follow your provider’s instructions about scheduling appointments after treatment ends. Your provider will likely continue to monitor you after treatment to check for signs that cancer has returned. This is especially the case in the first five years after treatment. Most cancers that recur do so within the first five years.

What questions should I ask my healthcare provider?

Questions to ask your provider include:

• Is the cancer hormone receptor-positive?
• What stage is the cancer?
• What treatments would you recommend?
• What treatment side effects should I expect?
• What is my prognosis?

Is it better to have HER2-positive or negative breast cancer?

As frustrating as the answer is — it depends. For example, HER2-positive breast cancers often grow faster than HER2-negative cancers. But they’re also eligible for therapies that can target HER2 proteins and slow growth. These treatments won’t work for HER2-negative cancers. Still, you may be eligible for hormone therapy if you have HR+ cancer cells. HR+/HER2- breast cancers have the best survival outlook of any breast cancer subtype.