Breast cancer is a complex group of diseases classified by specific molecular and genetic traits that determine how a cancer behaves and can be treated. Among these classifications, HER2-negative breast cancer is defined by having a normal amount of a protein called HER2 on the surface of its cells. This distinction is a primary factor in determining the course of the disease.
Understanding HER2 Status in Breast Cancer
Every cell in the breast has proteins called Human Epidermal growth factor Receptor 2 (HER2) on its surface. These receptors are involved in regulating normal cell growth, division, and repair. In a healthy breast, the HER2 gene provides instructions for making these proteins, but this balance is disrupted in some breast cancers, affecting how the disease is categorized and managed.
The distinction between HER2-positive and HER2-negative breast cancer lies in the quantity of these proteins. HER2-positive breast cancer is characterized by an overabundance of HER2 receptors, caused by a faulty gene that creates too many copies of itself. This excess of HER2 proteins can cause cancer cells to grow and divide at an accelerated rate. In contrast, HER2-negative breast cancer cells have a normal amount of these proteins, which influences the cancer’s behavior and response to specific therapies.
Diagnosis and Subtypes of HER2-Negative Cancer
To determine a tumor’s HER2 status, a small piece of breast tissue is obtained through a biopsy or during surgery. This tissue sample is then analyzed using specific laboratory tests. One common test is Immunohistochemistry (IHC), which measures the amount of HER2 protein on the surface of the cancer cells. Another test, Fluorescence In Situ Hybridization (FISH), evaluates the number of copies of the HER2 gene within the cells.
An IHC result of 0 or 1+ categorizes the cancer as HER2-negative. If the result is 2+, the status is considered borderline, and a FISH test is then performed to provide a more definitive result. A score of 3+ is considered HER2-positive. These tests are part of a broader analysis that also looks for the presence of hormone receptors, which are proteins that respond to the hormones estrogen (ER) and progesterone (PR).
This additional information is used to classify HER2-negative breast cancer into two main subtypes. The most common subtype is Hormone Receptor-positive (HR+)/HER2-negative breast cancer, which accounts for about 70% of all breast cancers. In this type, the cancer cells have receptors for estrogen, progesterone, or both, and these hormones fuel their growth. The other subtype is Triple-Negative Breast Cancer (TNBC), which is defined by the absence of these hormone receptors and normal levels of HER2.
Treatment Approaches
The treatment plan for HER2-negative breast cancer is highly dependent on its specific subtype, as determined by its hormone receptor status. For HR+/HER2-negative breast cancer, the primary treatment strategy involves therapies that target the hormones fueling the cancer’s growth. Hormone therapies, such as tamoxifen or aromatase inhibitors, work by either blocking hormone receptors on cancer cells or by reducing the amount of estrogen in the body.
In addition to hormone therapy, targeted therapies have become a standard of care for HR+/HER2-negative breast cancer. CDK4/6 inhibitors are a class of drugs that interfere with specific proteins involved in cell division. By blocking these proteins, these inhibitors can slow down the growth and spread of cancer cells. Chemotherapy may also be used for more advanced or aggressive tumors.
For individuals diagnosed with Triple-Negative Breast Cancer (TNBC), the treatment landscape is different due to the absence of hormone and HER2 receptors. Chemotherapy has long been the main treatment for TNBC, as the cancer cells do not respond to hormone or HER2-targeted therapies. Recent advancements have introduced new options like immunotherapy, which helps the body’s immune system recognize and attack cancer cells. For patients with an inherited BRCA gene mutation, PARP inhibitors offer a targeted approach by blocking a DNA repair pathway.
Regardless of the subtype, local treatments like surgery and radiation therapy are frequently used to remove the primary tumor and treat the surrounding area.
Prognosis and Follow-Up Care
The long-term outlook for an individual with HER2-negative breast cancer is influenced by a variety of factors, including the stage of the cancer at diagnosis, its grade, and its specific subtype. HER2-negative cancers that are also hormone receptor-positive tend to have a more favorable prognosis compared to triple-negative breast cancer. This is largely because there are more targeted treatment options available for HR-positive cancers. The stage of the cancer remains a primary determinant of survival rates.
Following the completion of initial treatment, a follow-up care plan is put in place to monitor for any signs of recurrence and to manage any long-term side effects of treatment. This ongoing care involves regular visits with the medical team, including physical exams and discussions about any new symptoms. Surveillance imaging, such as annual mammograms, is a standard part of follow-up to check for any changes in the breast tissue.
Depending on the type of treatment received, patients may also need to manage long-term side effects, which can range from joint pain associated with aromatase inhibitors to the risk of lymphedema after surgery. The follow-up plan is personalized to each individual’s situation, taking into account the specifics of their diagnosis and treatment history. This proactive approach to long-term management supports overall health and well-being.