The Nottingham Histologic Grade (NHG) is a standardized method pathologists use to evaluate the appearance and growth pattern of breast cancer cells. This scoring system measures tumor differentiation, indicating how aggressive the cancer cells are likely to behave. The final score, which ranges from 3 to 9, helps predict the tumor’s rate of growth and potential for spread. A Nottingham Score of 6 is categorized as Grade 2, placing it in the intermediate classification.
Understanding the Components of the Nottingham Score
The total Nottingham Score is derived from the assessment of three morphological features, each assigned a score from 1 to 3, which are then added together. The first feature is tubule formation, which evaluates how well cancer cells maintain the normal glandular structure of breast tissue. A score of 1 indicates excellent tubule formation, while a score of 3 indicates the near-total absence of these structures.
The second feature is nuclear pleomorphism, which assesses the size, shape, and uniformity of the cell nucleus. A score of 1 is given to cells that look most like normal cells, exhibiting minimal variation. Conversely, a score of 3 is assigned to cells showing marked variation and highly irregular features.
The third component is the mitotic rate, which measures how rapidly the cancer cells are dividing. Pathologists count the number of cell divisions (mitoses) visible within a defined area of the tissue sample. A low count results in a score of 1, indicating slow proliferation, while a high count receives a score of 3, signifying a high rate of cell division.
Interpreting Score 6 (Intermediate Grade)
A Nottingham Score of 6 falls into the Grade 2 category, described as a moderately differentiated or intermediate-grade tumor. This intermediate classification means the cancer cells exhibit a balance of features between the least and most aggressive types. They show moderate deviation from normal breast cells, suggesting a growth rate faster than Grade 1 but slower than Grade 3. This designation requires serious clinical attention but is associated with a more favorable long-term outlook compared to Grade 3.
Grade 1 tumors (scores 3 to 5) are considered well-differentiated; the cells closely resemble normal tissue and are generally slow-growing with the best prognosis. These tumors often retain normal glandular structure and have a low mitotic rate.
In contrast, Grade 3 tumors (scores 8 or 9) are considered poorly differentiated or high-grade. These cells look highly abnormal, lack discernible tubule formation, and divide very quickly, signifying the most aggressive biological behavior. The prognosis is generally less favorable, and they are more prone to recurrence.
A Score 6 tumor is positioned squarely between these extremes, reflecting a moderate degree of abnormality across the three scoring criteria. This score can result from moderate compromise in all three areas (e.g., 2 points each for tubule formation, nuclear pleomorphism, and mitotic rate), or from a mix of low and high scores (e.g., 1, 3, and 2). This intermediate nature means the tumor is actively growing but typically carries an intermediate risk of recurrence.
How Histologic Grade Influences Treatment Decisions
The histologic grade serves as one of several important biological factors guiding breast cancer treatment planning. While Grade 1 tumors are often treated successfully with local therapy and hormone therapy alone, Grade 3 tumors generally require more intensive systemic treatment, such as chemotherapy. The Grade 2 designation (Score 6) often represents a clinical “gray area” where the decision for aggressive systemic therapy is less straightforward.
For patients with a Grade 2 tumor, the treatment team integrates the score with other prognostic information, including tumor size, lymph node involvement, and hormone receptor status (Estrogen Receptor, Progesterone Receptor, and HER2 status). A small, lymph node-negative Grade 2 tumor might be managed without chemotherapy, especially if it is strongly hormone receptor-positive. Conversely, a larger Grade 2 tumor or one with lymph node involvement may lead to recommending chemotherapy.
Because of this ambiguity, Grade 2 tumors are frequently candidates for additional diagnostic testing, such as multi-gene genomic assays like Oncotype DX or MammaPrint. These tests analyze the expression levels of several genes to calculate a recurrence score, providing a more refined estimate of the tumor’s biological risk. This genomic information helps clarify whether the benefit of adding chemotherapy outweighs the potential side effects.