If you have very low levels of the HER2 protein, your tumor may be classified as HER2-low breast cancer. If your tumor has none of the protein, your tumor will be classified as HER2-negative. It’s important to know your HER2 status, because this information will determine your treatment options. About 15 to 20 percent of breast cancers are HER2-positive. If the possibly cancerous area or tumor can’t be reached by a core needle biopsy, a surgeon will perform a surgical biopsy to remove tumor tissue for evaluation. Once a biopsy is done, your doctor will administer one of these two tests to determine if your cancer is HER2 positive.
Immunohistochemistry (ICH) test This measures the amount of HER2 protein on the cancer cells. A reading of 0 to 1 is considered HER2-negative. If it’s 2+ it is HER2-low. If it is 3+, the cancer is HER2-positive.
Fluorescence in situ hybridization (FISH) test This assesses how many copies you have of the HER2 gene. Multiple copies of this gene means there’s more HER2 protein, which leads to cancer. This test may be given in addition to an IHC test if the results were borderline.
Some HER2 test results can come back wrong, so you might want to get evaluated more than once. It’s also possible for a breast cancer that was initially diagnosed as HER2-positive to develop into HER2-negative cancer, and vice versa. If your cancer returns or spreads, your doctor may test your HER2 status again. There’s the numerical staging system that’s commonly used to give a description of how large the tumor is and how far the cancer has spread. These are the five stages of cancer — stage 0, stage 1, stage 2, stage 3, or stage 4. The lower the number, the smaller and more localized the cancer will be. You can be HER2-positive or HER2-low at any of these stages. Stage 0 breast cancer, which is noninvasive, is typically not tested for HER2 status. Then there’s a more complex version of this staging that doctors use to determine what kind of treatment your cancer should receive. This version takes more than tumor size and cancer spread into account and also considers whether your cancer is:
HER2-positiveEstrogen-receptor (ER) positive (this means that cancer cells need estrogen to grow)Progesterone-receptor (PR) positive (this means that cancer cells need progesterone to grow)
If you are ER or PR positive, this means your cancer is hormone-sensitive in addition to being HER2-positive. About 50 percent of HER2-positive breast cancers are hormone-sensitive.
ChemotherapySurgeryHER2-targeted therapiesHormone therapyRadiation
The combination of treatments, as well as the kinds of targeted therapies you’re given, will depend on how advanced the cancer is and whether it’s hormone-sensitive or recurrent. If your cancer is stage 1, you may have surgery and then be given chemotherapy plus HER2-targeted therapy afterward. The therapy will usually be trastuzumab, with or without pertuzumab, for up to a year. If your cancer is stage 2 or stage 3, you will likely be given chemotherapy and HER2-targeted therapy (usually trastuzumab with or without pertuzumab) before surgery to shrink the tumor, with another round of targeted therapy after surgery, for up to a year. If your cancer is hormone-sensitive, you may be given hormone therapy along with the targeted therapy. Hormone therapy is administered in pill form, and is given for 5 to 10 years. (This is different from the hormone therapy given to women approaching or going through menopause.) In some cases, cancers that are both HER2 and HR positive may not need chemotherapy. The targeted therapies mentioned above are designed to target the HER2 proteins on cancer cells in order to keep the cancer from growing. Like chemotherapy, they’re given intravenously (in IV form). Targeted therapies for HER2-positive cancer include:
Trastuzumab (Herceptin)Perjeta (pertuzumab)Kadcyla (ado-trastuzumab emtansine)Tykerb (lapatinib)Enhertu (fam-trastuzumab deruxtecan-nxki)Nerlynx (neratinib)
But even with these developments, HER2-positive cancer is still more likely to recur than other cancer types of cancer. It’s been estimated that cancer will come back and spread in about 30 percent of people who receive trastuzumab, which is the most commonly used targeted therapy. Life expectancy after diagnosis can be affected by your hormone receptor status. According to the National Cancer Institute, the five-year survival rate for those whose breast cancers are both HER2 and HR-positive is 90.7 percent. This means that 90.7 percent of women diagnosed with that cancer subtype will still be alive five years after diagnosis. The five-year survival rate for those whose cancers are HER2-positive but HR-negative is 84.8 percent. This means that 84.8 percent of women diagnosed with that cancer subtype will still be alive five years after diagnosis. Metastatic cancer is stage 4 cancer. The following targeted therapies are used to treat metastatic HER2-positive cancer:
Perjeta (pertuzumab)Tykerb (lapatinib)Enhertu (fam-trastuzumab deruxtecan-nxki)Nerlynx (neratinib)Tukysa (tucatinib)Margenza (margetuximab-cmkb)
These medications may help those with metastatic HER2-positive breast cancer live longer, and may also increase the time they can live without their tumors growing or spreading. This type of cancer is thought to be a good candidate for a vaccine, as it’s one of the few cancers that provokes an immune response. Researchers are hoping to harness this reaction and train it to help prevent the cancer from developing or returning, or to treat existing tumors. No vaccine has been approved yet by the FDA, but there are dozens of clinical trials underway. There are hundreds of clinical trials currently ongoing or completed for HER2-positive breast cancer. You can visit ClinicalTrials.gov to see if there are any in your area that are still recruiting. About 80 percent of all breast cancers are HER2-negative. You may be diagnosed with two other subtypes of cancer if you’re found to be HER2-negative. These are:
Hormone-sensitive cancer This means your cancer has also tested positive for receptors for estrogen (ER), progesterone (PR), or both, and can be treated with hormone therapy. About 68 percent of breast cancer is HER2-negative and hormone-sensitive.Triple-negative cancer This means your cancer isn’t HER2-positive, ER-positive, or PR-positive. About 10 to 15 percent of all breast cancer is triple negative.
Immunohistochemistry (ICH) test A reading of 0 to 1+means the cancer is HER2 negative.Fluorescence in situ hybridization (FISH) test Multiple copies of this gene means there’s more HER2 protein, which leads to cancer. This test may be given in addition to an IHC test if the results were borderline.
As stated earlier, some breast cancers that are HER2-positive can turn into HER2-negative cancer, and vice versa. And since it’s also possible that HER2 test results can come back wrong, you might want to have the test done more than once. If your ICH test comes back borderline, you and your doctor might want to do another test. Advances in testing have also led to the creation of an additional HER2 reading: HER2-low. You may receive a diagnosis of HER2-low breast cancer when you have either a 1+ score on an IHC test or a 2+ score on an IHC test plus a negative FISH test result. About half of all breast cancers are HER2-low. Treatment may include a combination of two or more of the following:
ChemotherapySurgeryTargeted therapyHormone therapyRadiation
Since most HER2-negative cancers are hormone sensitive — that is, they’re ER or PR-positive or both — they can be treated very effectively with hormone therapy given after surgery. There are a few targeted therapies available for HER2-negative cancer. They include:
Verzenio (abemaciclib)Afinitor (everolimus)Ibrance (palbociclib)Faslodex (fulvestrant)
The FDA has recently approved a treatment for HER2-low breast cancer that’s metastatic. It’s a targeted therapy called Enhertu (trastuzumab deruxtecan), which is also used to treat HER2-positive cancer. But if HER2-negative breast cancer is also triple negative, prognosis is not as good. The five-year survival rate for those whose cancers are HER2-negative and HR-negative is 77.1 percent. But there is research being done on vaccines for triple-negative breast cancer, which does provoke an immune response, and which requires HER2-negative status as part of the diagnosis. Additional reporting by Cathy Cassata.
