Understanding the specific characteristics of cancer cells is crucial for effective breast cancer management. One significant characteristic is the Human Epidermal Growth Factor Receptor 2 (HER2) status, which plays a crucial role in diagnosing the disease and guiding treatment decisions. Determining this status provides important information about how the cancer might behave and which therapies are most likely to be beneficial.
Understanding HER2 Status
Human Epidermal Growth Factor Receptor 2 (HER2) is a protein on the surface of breast cells that regulates cell growth and division. In certain breast cancers, the HER2 gene makes too many copies, leading to an excess of HER2 protein. This overexpression stimulates cancer cells to grow and divide rapidly.
HER2 status is determined by laboratory tests on a tissue sample from a biopsy or surgery. The primary tests are immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). IHC measures the amount of HER2 protein on the cell surface, with scores from 0 to 3+. A score of 0 or 1+ indicates HER2-negative status, while 3+ signifies HER2-positive.
If an IHC score is 2+, a FISH test is usually performed to confirm HER2 status. FISH assesses the number of HER2 gene copies within the cancer cells. A normal amount of HER2 genes or proteins means the cancer is HER2-negative. These tests inform oncologists about the cancer’s biology, which impacts treatment planning.
Interpreting HER2-Negative Breast Cancer
When breast cancer is identified as HER2-negative, it means the cancer cells do not have an excessive amount of HER2 protein on their surface. This indicates the cancer’s growth is not primarily driven by the HER2 pathway. Approximately 78% to 81% of breast cancers are classified as HER2-negative, making it the more common type.
The absence of HER2 overexpression is generally considered a favorable characteristic. These cancers tend to exhibit different growth patterns compared to HER2-positive cancers, which are often more aggressive. HER2-negative tumors are less likely to grow or spread as rapidly.
Therapies specifically designed to target the HER2 protein will not be effective for these cancers. Instead, the cancer’s behavior and response to treatment are influenced by other factors, such as hormone receptor status. HER2-negative breast cancers can be hormone receptor-positive (responding to estrogen and/or progesterone) or triple-negative (lacking hormone receptors and HER2 overexpression). The lack of HER2 as a driving force allows for different therapeutic strategies that target other mechanisms of cancer growth.
Treatment Strategies for HER2-Negative Cancer
Treatment for HER2-negative breast cancer is tailored to the individual, considering the cancer’s stage, grade, and hormone receptor status. Since these cancers do not overexpress the HER2 protein, therapies that specifically target HER2, such as trastuzumab, are not utilized.
Surgery is often the initial treatment, aiming to remove the tumor. This may involve a lumpectomy (removing the tumor and a margin of healthy tissue) or a mastectomy (removing the entire breast). Following surgery, radiation therapy is frequently recommended, particularly after a lumpectomy, to eliminate any remaining cancer cells and reduce the risk of local recurrence.
Chemotherapy is a common systemic treatment option for HER2-negative breast cancer, especially for larger tumors, lymph node involvement, or more aggressive subtypes like triple-negative breast cancer. These drugs interfere with the growth and division of cancer cells throughout the body. Chemotherapy can be administered before surgery (neoadjuvant therapy) to shrink the tumor or after surgery (adjuvant therapy) to destroy any microscopic cancer cells.
For HER2-negative cancers that are also hormone receptor-positive, hormone therapy plays a central role. These treatments block the effects of hormones like estrogen and progesterone or reduce their production, as these hormones can fuel cancer growth. Examples include tamoxifen (blocking estrogen receptors) and aromatase inhibitors (lowering estrogen levels in postmenopausal women). Targeted therapies, such as CDK4/6 inhibitors, may also be used with hormone therapy for advanced cases.
Prognosis for HER2-Negative Cancer
The prognosis for individuals with HER2-negative breast cancer is typically considered favorable, especially when compared to HER2-positive cancers before the advent of targeted HER2 therapies. The absence of HER2 overexpression means the cancer lacks a specific aggressive growth driver, often translating to a less aggressive disease course and better responsiveness to standard treatments.
The overall prognosis is influenced by several other factors beyond HER2 status alone. These include the cancer’s stage at diagnosis (tumor size and spread to lymph nodes or distant parts of the body) and grade (how abnormal the cancer cells look and how quickly they are likely to grow). The presence or absence of hormone receptors also significantly impacts prognosis and treatment options.
For localized HER2-negative breast cancers, the five-year survival rate can be very high, nearing 100% for hormone receptor-positive cases. Even if the cancer has spread to nearby lymph nodes, survival rates remain substantial. While HER2-positive cancers were historically more aggressive, highly effective HER2-targeted therapies have significantly improved their outcomes, narrowing the prognostic gap. HER2-negative status means the cancer is less likely to be driven by aggressive HER2 overexpression and is often more amenable to conventional and hormone-based therapies, contributing to a generally positive outlook.