The Ki-67 score measures how quickly breast cancer cells are multiplying. This widely used biomarker helps doctors assess a tumor’s aggressiveness, as uncontrolled cell division is a defining characteristic of cancer. By determining the proportion of tumor cells actively preparing to divide, the score helps predict the cancer’s behavior and guide treatment planning.
The Biological Role of Ki-67 in Cell Division
Ki-67 is a large nuclear protein found exclusively within the cell’s nucleus. The protein acts as a direct marker for cell proliferation because it is only present when a cell is actively growing and dividing. It is detectable throughout the active phases of the cell cycle, including G1 (growth), S (DNA synthesis), G2 (preparation for division), and M (mitosis) phases.
The protein is notably absent in cells that are in the G0 phase, which is a resting state where cells are not preparing to divide. When a cancer cell exits the G0 phase and re-enters the cycle, the Ki-67 protein begins to accumulate. Because the protein is continuously degraded during the resting phase, the level of Ki-67 reflects the overall pace of tumor growth.
A high level of Ki-67 indicates a high “growth fraction,” meaning a large percentage of cells are multiplying. Conversely, a low Ki-67 level suggests that most cells are in a quiescent or slow-dividing state. The presence of Ki-67 helps to quantify the tumor’s proliferative potential, which is a major factor in determining its biological aggressiveness.
How Ki-67 is Measured and Reported
The Ki-67 score is determined using Immunohistochemistry (IHC) on a tissue sample, typically from a biopsy. This method uses a specific antibody designed to bind only to the Ki-67 protein within the tumor cells. Once the antibody binds, a chemical reaction produces a visible color change, which stains the nuclei of the proliferating cells.
A trained pathologist examines the stained tissue under a microscope to calculate the Ki-67 score, also known as the Ki-67 labeling index. The score is reported as a percentage, representing the proportion of invasive tumor cells that have stained positive for the Ki-67 protein. For an accurate measurement, the pathologist typically counts several hundred tumor cells across different areas of the tissue sample.
The visual scoring process requires careful attention to pre-analytical factors, such as how the tissue was collected and preserved, as these can affect the final staining quality. Standardized visual scoring methods have been established to minimize variability in reporting. Despite these efforts, the scoring process can still be challenging, particularly for intermediate scores, which is why a precise, standardized methodology is so important.
Interpreting Ki-67 Scores and Tumor Subtypes
The Ki-67 score is a powerful prognostic tool, as a higher percentage generally correlates with a higher-grade tumor and a greater potential for spread. Scores are often categorized into low and high ranges to help determine the tumor’s biological profile. While there is no single, universally agreed-upon cutoff, an index of 5% or less is often considered very low, and a score of 30% or more is typically regarded as high, indicating a rapidly growing tumor.
For a large number of breast cancers that are Estrogen Receptor-positive (ER+) and HER2-negative, the Ki-67 score is used to distinguish between two important molecular subtypes: Luminal A and Luminal B. Tumors classified as Luminal A are typically characterized by a low Ki-67 score, often cited as under 14% or 20% depending on the institution, and are considered slow-growing with a favorable prognosis. These tumors are highly responsive to hormonal therapy.
In contrast, Luminal B tumors are also ER-positive and HER2-negative, but they are defined by a high Ki-67 score, often above 20%. These tumors are considered more proliferative and aggressive than Luminal A tumors. The higher proliferation rate in Luminal B tumors means they carry a greater risk of recurrence and may require more intensive treatment beyond hormonal therapy. The Ki-67 score is therefore a necessary piece of information to properly classify and understand the specific behavior of these common breast cancer types.
Applying Ki-67 to Breast Cancer Treatment Decisions
The Ki-67 score significantly influences the decision-making process for breast cancer treatment, especially for ER-positive, HER2-negative cases. A low Ki-67 score, which is characteristic of Luminal A tumors, suggests that the cancer is less aggressive and highly likely to respond well to endocrine therapy alone. In these cases, the risk of recurrence is low, and the benefit of adding chemotherapy is often considered minimal.
However, a high Ki-67 score, typical of Luminal B tumors, indicates a faster growth rate and a higher risk of recurrence, which changes the treatment calculation. For these more proliferative cancers, doctors are more likely to recommend systemic therapy, such as chemotherapy, in addition to endocrine therapy to aggressively target the fast-dividing cells. The score helps identify patients who are likely to gain a significant benefit from this more intensive approach.
The Ki-67 index can also be used to predict the effectiveness of neoadjuvant, or pre-surgery, therapy. Monitoring the change in the Ki-67 score after a short course of endocrine therapy can help predict long-term outcomes and inform whether a patient should switch to chemotherapy. For instance, a persistent high Ki-67 level after a few weeks of hormonal treatment suggests that the cancer is resistant to that therapy and may benefit more from switching to a chemotherapy regimen.