Most types of breast cancer produce similar symptoms and are discovered the same way—finding a strange new lump during a self-exam, or a healthcare provider spotting something suspicious during a mammogram. Yet on a deeper level, different types of breast cancer can behave very differently from one another. Usually, only a breast biopsy—when a tissue sample from a breast tumor is sent to the lab—can determine what specific type of breast cancer (or subtype) you have, as well as your breast cancer stage—meaning how far the cancer has already spread. These details will help determine your best treatment options and overall prognosis.
It’s crucial to get a biopsy if, like most people, you have invasive breast cancer, meaning the cancer has already spread beyond milk ducts or glands into the surrounding breast tissue. One key piece of information contained in the pathology report from your biopsy will be your HER2 status, which indicates whether your breast tumor tissue sample came up as HER2-positive or HER2-negative. The specific test within the report that determines your HER2 status is called an ImmunoHistoChemistry (IHC test), and it reveals to what extent your cancer cells have two types of receptor—HER2 receptors and/or hormone receptors—on their surface.
High levels of HER2 receptors (an IHC test score of 3+) are what lead to a diagnosis of HER2-positive breast cancer. This type of breast cancer results from “overexpression” (elevated levels) of a protein known as HER2 (human epidermal growth factor receptor) due to a mutation in the HER2 gene. Under normal circumstances, the HER2 protein aids in cell growth, but when is is over-abundant, it can spur growth of breast cancer cells. Representing about 20 percent of all breast cancer cases, HER2-positive breast cancer tends to be aggressive and spread quickly, as well as recur years after successful treatment. That said, it also usually responds well to highly effective treatments that work by interfering with production of HER2 proteins. Known as targeted therapies, HER2 inhibitors, or anti-HER2 therapies, these treatment options often have less severe side effects than other breast cancer treatments like standard chemotherapy.
That said, most breast cancers—close to 80 percent—are HER2-negative, meaning that the tissue sample sent out for biopsy contains little to no evidence of HER2 proteins (an IHC test score of 0 to 1+). When breast cancer is diagnosed as HER2-negative, the aforementioned targeted therapies are not an effective treatment option. HER2 status isn’t always clear-cut, however. Sometimes, biopsies reveal that breast cancer is “borderline” HER2 positive (an IHC test score of 2+). In this case, your oncology provider will likely request that your tissue sample be reevaluated using a method called a FISH test (short for “fluorescence in situ hybridization”) to clarify whether your cancer is HER2-positive or HER2-negative. Other biopsies have a result of HER2-low, which means that evidence of HER proteins was detected, but at low levels. HER2-low is a newly designated type of breast cancer that’s still being studied, but research has shown that people with this diagnosis may still respond well to certain HER2-targeted therapies, specifically the drug trastuzumab deruxtecan.
To summarize, being HER2-positive can mean more treatment options, even though your cancer is aggressive. Yet just because your breast cancer is HER2 negative doesn’t mean radiation and chemotherapy are the only options. Hormone receptor status is another important factor that can help open up additional treatment options. Both HER2-positive and HER2-negative breast cancer can be hormone receptor-positive (or negative). Hormone receptor-positive (HR-positive) means that breast cancer cells have estrogen receptors (ER-positive) or progesterone receptors (PR-positive), or both. Hormone receptor-positive types of breast cancer can be treated using hormone therapy, also known as endocrine therapy, which blocks production of the specific hormone that is helping cancer to grow. If you’re HER2-positive and hormone receptor-positive, you may be able to take advantage of hormone therapy as well as HER2 targeted therapies. The term “triple positive breast cancer” means that you are HER2-positive, ER-positive, and PR-positive.
On the opposite end of the spectrum, breast cancer that is HER2-negative and also hormone receptor-negative is known as triple-negative breast cancer and represents about 10 to 15 percent of all cases. This aggressive type of breast cancer, which is most common among women younger than age 40 who are Black or who have the BRCA1 gene mutation, has the most limited range of treatment options, since it does not respond to HER2-targeted therapies or to hormone therapies.
Finally, there is another type of breast cancer diagnosis to layer in: metastatic breast cancer, which means that the cancer has spread beyond the breast to another part of the body, usually the bones, lungs, brain, or liver. Metastatic breast cancer can no longer be cured, but there are ever-evolving treatment options that can help manage its spread and symptoms, sometimes for many years. This is especially true for HER2-positive metastatic breast cancer, since anti-HER2 therapies have been shown to improve survival rates for metastatic breast cancer as well as early stage cancer. (Here’s more on what to expect after a HER2-positive metastatic breast cancer diagnosis.)
There’s one important factor to keep in mind regardless of your HER2 status: Breast cancers that are designated as HER2-positive can become HER2-negative later on, and the reverse is also true: HER2-negative breast cancer can become HER2-positive over the course of time. If your breast cancer recurs in the future, you’ll likely need another biopsy to reestablish your HER2 status and make sure you’re getting the treatments most likely to keep you one step ahead of cancer’s spread.
Petra Guglielmetti is a health, wellness, and beauty journalist who taps into a broad network of doctors, scientists, and medical experts to write in-depth service articles for leading publications like Glamour, Health, Real Simple, and Parents.
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