The Ki-67 score is a standard inclusion in the pathological assessment of breast cancer tumors. It functions as a quantitative biomarker, providing pathologists and oncologists with information about the rate at which cancer cells are dividing within a tumor sample. This measurement helps determine how quickly a tumor is growing, which is linked to its potential aggressiveness and the patient’s prognosis. Understanding this score is important for classifying the tumor and choosing the most appropriate course of treatment.
The Biological Function of the Ki-67 Protein
The Ki-67 score represents the percentage of tumor cells that are actively proliferating, a measurement made possible by the presence of the Ki-67 protein itself. This protein, also known as MKI67, is a nuclear protein found exclusively in cells that are preparing for or undergoing division. Its presence serves as a marker for cell proliferation because it is synthesized throughout the active phases of the cell cycle: G1, S, G2, and M phases.
Conversely, the Ki-67 protein is virtually absent when cells are in the resting state, known as the G0 phase. Pathologists use an antibody that binds to this protein to stain the tumor sample and count the percentage of stained (Ki-67 positive) nuclei. A higher percentage of Ki-67 positive cells indicates a larger “growth fraction,” meaning a greater proportion of the tumor population is actively multiplying.
Interpreting Ki-67 Score Ranges
The Ki-67 score, often referred to as the labeling index, is a percentage that reflects the tumor’s proliferative activity. This percentage is directly related to the tumor’s likely biological behavior and is generally used as a prognostic factor. A low Ki-67 score suggests a slower-growing tumor, which is associated with a more favorable long-term outlook.
Tumors with a Ki-67 index of 10% or less are classified as having a low proliferative rate, suggesting a less aggressive form of cancer. This low activity means the cells are not multiplying rapidly, and the tumor is considered less likely to spread quickly. In contrast, a high Ki-67 score, often defined as 20% or higher, suggests a rapidly proliferating tumor. This high rate of cell division indicates a more aggressive tumor with a greater potential for early recurrence or metastasis.
The range between these two extremes, often between 10% and 20%, is considered intermediate and presents a challenge for interpretation. Clinical guidelines have used thresholds ranging from 14% to 30% to define higher risk categories. Regardless of the exact cutoff, the score provides a measure of intrinsic tumor biology: the higher the number, the more aggressive the tumor is likely to be.
Guiding Treatment Decisions
The Ki-67 score is an important factor oncologists use to tailor treatment, especially for estrogen receptor-positive (ER+) and HER2-negative breast cancers. This score helps to sub-classify these tumors into two biological groups: Luminal A and Luminal B.
Luminal A tumors are characterized by a low Ki-67 score, suggesting a low rate of proliferation and a better prognosis. For these patients, treatment often focuses on endocrine (hormone) therapy alone, as the potential benefit of adding chemotherapy is generally low.
Conversely, Luminal B tumors are defined by a high Ki-67 score, which signifies a high proliferative rate and an increased risk of recurrence. The aggressive nature of Luminal B tumors means they are more likely to benefit from the addition of chemotherapy, alongside endocrine therapy. The Ki-67 score is thus a primary tool for deciding whether to recommend chemotherapy, which preferentially targets fast-dividing cells, to reduce the risk of recurrence.
Variability and Standardization Challenges
Despite its clinical utility, the Ki-67 score is subject to significant variability, which complicates its use as a universal, standalone metric. A major challenge stems from the lack of a fully standardized method for counting the positive cells across different pathology laboratories.
Pathologists may use different protocols, such as assessing the average Ki-67 across the entire tumor or focusing on “hot spots,” which are areas of highest proliferation. These differences in counting methodology can lead to substantial inter-observer variability, meaning different pathologists may assign a different Ki-67 score to the same tumor sample.
Furthermore, variations in the pre-analytical steps, such as how the tissue is handled, fixed, and stained, can also influence the final percentage reported. This lack of standardization has led to consensus groups recommending specific scoring protocols, but the score should always be interpreted alongside other factors like tumor grade and hormone receptor status.