Human Epidermal Growth Factor Receptor Negative

Human epidermal growth factor receptor (HER) negative refers to a classification used primarily in breast cancer when tumor cells do not produce excess amounts of certain growth factor receptors. Understanding this status is crucial for determining the most appropriate treatment approach for patients.

Table of contents

• What is Human Epidermal Growth Factor Receptor Negative?
• The Epidermal Growth Factor Receptor Family
• HER2-Negative Breast Cancer
• Testing for HER Status
• Treatment Implications

What is Human Epidermal Growth Factor Receptor Negative?

Human epidermal growth factor receptor (HER) negative is a term used to describe cancer cells, particularly breast cancer cells, that do not make too much of certain proteins called receptors. These receptors normally sit on the surface of cells and help control how cells grow and divide^[2].

When doctors say a cancer is HER-negative, it means the cancer isn’t making a lot of extra receptor proteins. This is different from HER-positive cancers, where cells produce too many of these receptors, causing the cancer to grow more aggressively^[14].

The Epidermal Growth Factor Receptor Family

The epidermal growth factor receptor family is a group of related proteins that work together to help cells function. This family consists of four members: EGFR (also called ErbB1 or HER1), ErbB2 (called HER2), ErbB3 (HER3), and ErbB4 (HER4)^[2].

These receptors are single-chain proteins that span the cell membrane. They have three main parts: an outer section that can bind to substances outside the cell, a middle section that crosses through the cell membrane, and an inner section that sends signals inside the cell. When the right substances attach to the outer part of these receptors, they trigger a chain of events inside the cell that can affect cell growth and division^[2].

Under normal conditions, these receptors help regulate healthy cell growth. However, when something goes wrong with these receptors or the genes that make them, cells can begin to grow out of control. This abnormal growth is what happens in many cancers^[2].

HER2-Negative Breast Cancer

HER2-negative breast cancer is the most common type of breast cancer. About four out of five breast cancers do not have extra HER2 receptors^[14]. When a cancer is HER2-negative, it means the cancer cells aren’t making excessive amounts of the HER2 protein, which is a receptor that can make cancer grow faster when it’s overproduced.

HER2-negative breast cancer generally has a better outlook than HER2-positive breast cancer because it tends to be less aggressive^[14]. Most HER2-negative breast cancers are also positive for hormone receptors, which are proteins that respond to hormones like estrogen and progesterone. Almost 70 percent of breast cancers are both hormone receptor-positive and HER2-negative^[14].

A smaller portion of breast cancers, about 10 to 15 percent, are negative for both hormone receptors and HER2. These are called triple-negative breast cancers^[14]. Recently, doctors have also identified a category called HER2-low, which refers to cancers that have some HER2 proteins but not enough to be considered HER2-positive^[9].

Testing for HER Status

Doctors cannot tell whether a breast cancer is HER-negative or HER-positive just by examining a patient. Instead, they need to test a small piece of the tumor, which is obtained either during a biopsy (a procedure to remove a tissue sample) or during surgery^[14].

Two common tests are used to determine HER2 status. The IHC test (ImmunoHistoChemistry) uses a chemical dye to stain the HER2 proteins and gives a score from 0 to 3+. A score of 0 to 1+ is considered HER2-negative, while a score of 3+ is considered HER2-positive^[18].

The FISH test (Fluorescence In Situ Hybridization) uses special labels that attach directly to the HER2 genes. This test can confirm whether cancer cells have too many copies of the HER2 gene^[18].

It’s important to know that cancers can change over time. A cancer that starts out as HER2-negative could potentially become HER2-positive later, or vice versa. If breast cancer returns after treatment, doctors should consider testing it again to check if the HER2 status has changed^[18].

Treatment Implications

Knowing whether a cancer is HER-negative is essential because it helps doctors choose the right treatment. Some breast cancer treatments work by specifically targeting HER2 receptors. If a cancer is HER2-negative, these targeted therapies won’t be effective, and doctors will recommend other treatment options^[14].

For hormone receptor-positive, HER2-negative breast cancer, doctors typically recommend endocrine therapy (also called hormone therapy), which blocks the effects of hormones that can fuel cancer growth. This is often combined with other medications such as CDK4/6 inhibitors, which help stop cancer cells from dividing^[10].

For triple-negative breast cancer (which is negative for both hormone receptors and HER2), treatment usually involves chemotherapy, which uses drugs to kill rapidly dividing cells. Recent advances have also brought new treatment options, including certain types of immunotherapy for some triple-negative breast cancers^[13].

In recent years, researchers have developed new treatments even for HER2-low breast cancers, which were previously treated the same way as HER2-negative cancers. These new therapies include powerful antibody-drug conjugates that can target cells with even small amounts of HER2^[9].