What is hormone receptor negative HER2 positive breast cancer

Hormone receptor negative HER2 positive breast cancer is a specific type of breast cancer where cancer cells do not have hormone receptors for estrogen or progesterone, but they do produce excessive amounts of a protein called HER2 (human epidermal growth factor receptor 2). These cancer cells lack the receptors that would allow hormones like estrogen and progesterone to fuel their growth, but they have high levels of HER2 protein on their surface^[1][2].

Around 15 to 20 percent of all breast cancer cases are HER2 positive, meaning that the breast cancer cells produce excessive amounts of the HER2 protein, which promotes the growth of this type of breast cancer^[2]. In normal, non-cancerous cells, HER2 is responsible for normal cell growth and other essential cellular processes. However, when excessive levels of HER2 are present in cancer cells, this leads to fast-growing tumors^[2].

HER2 positive breast cancer may be hormone receptor positive, meaning it needs hormones estrogen and progesterone to grow and reproduce, or it may be hormone receptor negative^[2]. When breast cancer is hormone receptor negative and HER2 positive, it means the cancer cells don’t respond to hormones but do have high levels of HER2 that drive their growth.

This type of breast cancer can be more aggressive than some HER2 negative breast cancers^[2]. The cancer grows faster because the excess HER2 protein on the surface of cancer cells signals them to grow and divide rapidly.

Testing and diagnosis

When you are diagnosed with breast cancer, breast tissue sampled by a biopsy or after surgery is sent to a specialist doctor called a pathologist who will report on several features in the sample^[2]. This includes testing the status of important markers such as the estrogen receptor, progesterone receptor, and HER2. These results help your treating doctor determine the best treatments for you, which may include hormonal or targeted drugs^[2].

All invasive breast cancers are tested for HER2 levels. This testing is done in a hospital laboratory on a sample of breast cancer tissue removed during a biopsy or surgery. The results are usually available within 1 to 3 weeks^[18].

There are various tests to measure HER2 levels. A test called IHC (immunohistochemistry) is usually done first. It involves a special staining process performed on a sample of breast cancer tissue. The test results are reported as a score ranging from 0 to 3. A score of 0 or 1+ means the breast cancer is HER2-negative. A score of 2+ is considered borderline. A score of 3+ means the breast cancer is HER2-positive^[18].

Breast cancers with a borderline result (2+) should be retested using more specialized techniques. These tests will give a result of HER2-positive, HER2-low, or HER2-negative^[18].

Breast cancers are also tested to determine if they have hormone receptors for estrogen and progesterone. Breast cancers that have 1 percent or more of cells staining positive for estrogen receptor are considered estrogen receptor-positive, and those with 1 percent or more of cells with progesterone receptor staining are considered progesterone receptor-positive^[5]. When a breast cancer has neither of these hormone receptors but does have high HER2 levels, it is classified as hormone receptor negative HER2 positive.

Treatment approaches

If your breast cancer is HER2-positive but hormone receptor negative, you will usually be offered a targeted therapy (also called biological therapy) alongside or after chemotherapy^[18]. Because the cancer cells don’t have hormone receptors, hormone therapies that work for hormone receptor-positive cancers will not be effective for this type.

Targeted therapies are medications that specifically block the HER2 protein or interfere with how it signals cancer cells to grow. Several targeted therapies may be offered for HER2 positive breast cancer. These include trastuzumab (brand name Herceptin), pertuzumab and trastuzumab (brand name Phesgo), trastuzumab emtansine (brand name Kadcyla), trastuzumab deruxtecan (brand name Enhertu), neratinib (brand name Nerlynx), and tucatinib (brand name Tukysa)^[18].

Chemotherapy is medicine that kills cancer cells. You can take it as pills or receive it through an IV (intravenous line)^[12]. Many different chemotherapy drugs are used, either alone or in combination, to treat HER2 positive breast cancer. Your doctor will prescribe a chemotherapy drug based on your past treatments, your preferences, any other conditions you have, and your risk of side effects^[12].

Some women also have surgery or radiation to prevent or treat symptoms^[12]. The specific treatment plan will depend on the stage of your cancer, your overall health, and other factors unique to your situation.

It’s important to understand that while hormone receptor negative HER2 positive breast cancer doesn’t respond to hormone therapies like tamoxifen or aromatase inhibitors, the availability of HER2-targeted therapies means that this type of breast cancer can be treated effectively. Your healthcare team will work with you to develop a treatment plan that is right for your specific situation.