The stage and grade of a breast cancer tumor are important prognostic factors. Learn what staging and grade mean, as well as how they are calculated.

Staging

What is Staging?

The pathologic stage of breast cancer is a measure of how advanced a patient's tumor is. Breast cancer stage ranges from Stage 0 (pre-invasive disease) to Stage IV (metastatic disease). Stage is a prognostic factor, and in broad generalization, "low stage" cancers (Stages 0-II) tend to have better long term outcome than "high stage" cancers (Stages III-IV). Understanding a patient's stage helps the clinical team determine the right treatment.

The "pathologic stage" of a cancer takes into consideration the characteristics of the tumor ("T") and the presence of any lymph nodes metastases ("N") or distant organ metastases ("M"). These features are assigned individual scores called the pathologic T stage (T0-4), N stage (N1-3) and M stage (M0-1) are combined to form a final overall pathology stage (stage 0-IV). The pathologic stage is determined by the findings at the time of surgery and is different from the "clinical stage," which is the stage estimated based upon the findings on clinical exam and radiology.

The American Joint Committee on Cancer (AJCC) published a revised protocol for the examination of specimens from patients with invasive breast cancers in 2018, which is the 8th edition of cancer staging. This most recent edition calls the pathologic stage the "AJCC Anatomic Stage Group." The stage listed in the pathology report will be this Anatomic Stage Group.

Unique to breast cancer, the AJCC 8th Edition created a second, new category of stage classification, called the "AJCC Prognostic Stage Group." The "AJCC Prognostic Stage Group" incorporates the tumor's nuclear grade, results from ER, PR and HER2 testing as well as the results of multigene tests (if performed) into the scoring. This stage group should be discussed with an oncologist or breast surgeon.

How are the Tumor (T), lymph Node (N) and Metastasis (M) stage scores determined?   

Primary Tumor (pT)
pT0 No evidence of primary tumor
pTis Ductal carcinoma in situ, or Paget’s disease
pT1 Invasive tumor ≤2.0 cm in greatest dimension
pT1mi: Tumor ≤0.1 cm in greatest dimension (microinvasion)
pT1a: Tumor >0.1 cm but ≤0.5 cm in greatest dimension
pT1b: Tumor >0.5 cm but ≤1.0 cm in greatest dimension
pT1c: Tumor >1.0 cm but ≤2.0 cm in greatest dimension
pT2 Invasive tumor >2.0 cm but ≤5.0 cm in greatest dimension
pT3 Invasive tumor >5.0 cm in greatest dimension
pT4 Invasive tumor of any size with direct extension to the chest wall and/or to the skin, or inflammatory breast carcinoma
pT4a: Tumor extension to chest wall (does not include tumors limited to pectoralis muscle)
pT4b: Tumor extension into the skin with ulceration
pT4c: Tumor invasion into the chest wall and the skin
Inflammatory breast carcinoma (requires clinical symptoms)
Regional Lymph Nodes (pN)
pNX Regional lymph nodes cannot be assessed (eg, previously removed, or not removed)
pN0 No regional lymph node metastasis identified histologically, or isolated tumor cells only
pN0 (i+): Isolated tumor cells (ITC): malignant cells <0.2 mm and no more than 200 cells
pN1mi Micrometastases (malignant cells measuring 0.2 mm - 2.0 mm,or more than 200 cells)
pN1a Metastases in 1 to 3 axillary lymph nodes (at least one measuring > 2.0 mm)
pN2a Metastases in 4 to 9 axillary lymph nodes
pN3a Metastases in 10 or more axillary lymph nodes
Distant Metastasis (M) (required only if confirmed pathologically in this case)
pM0 No metastases
pM1 Histologically proven metastasis larger than 0.2 mm

How is the pathologic stage (0-IV) determined?   

Pathologic Stage 0 T stage score N stage score M stage score
0 Tis N0 M0
Pathologic Stage I T stage score N stage score M stage score
IA T1 N0 M0
IB T0 N1mi M0
IB T1 N1mi M0
Pathologic Stage II T stage score N stage score M stage score
IIA T0 N1 M0
IIA T1 N1 M0
IIA T2 N0 M0
IIB T2 N1 M0
IIB T3 N0 M0
Pathologic Stage III T stage score N stage score M stage score
IIIA T0 N2 M0
IIIA T1 N2 M0
IIIA T2 N2 M0
IIIA T3 N1 or N2 M0
IIIB T4 N0, N1 or N2 M0
IIIC any T score N3 M0
Pathologic Stage IV T stage score N stage score M stage score
IV any T score any N score M1

An Accurate Diagnosis is Essential

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Grade

What is Grade?

The grade of a breast cancer is a prognostic factor and is representative of the "aggressive potential" of the tumor.  In a broad generalization, "low grade" cancers tend to be less aggressive than "high grade" cancers. Determining the grade is thus very important, and clinicians use this information to help guide treatment options for patients.

There are different "scoring systems" available for determining the grade of a breast cancer. One of these systems is the Nottingham Histologic Score system (also termed “the Elston-Ellis modification of Scarff-Bloom-Richardson grading system”). In this scoring system, there are three factors that the pathologists take into consideration:

  1. the amount of gland formation (the cell “differentiation,” or how well the tumor cells are trying to recreate normal glands)

  2. the nuclear features (the degree of "pleomorphism" or how "ugly" the tumor cells look)

  3. the mitotic activity (how much the tumor cells are dividing, or proliferating)

Each of these features is scored from 1-3, and then the scores is added to give a final total score ranging from 3-9. The final total score is used to determine the grade in the following way:

Grade I tumors have a total score of 3-5

Grade II tumors have a total score of 6-7

Grade III tumors have a total score of 8-9

How is Grade Calculated?   

Glandular/Tubular Differentiation Nuclear Pleomorphism Mitotic Count*
Score 1 >75% of tumor forms glands Uniform cells with small nuclei similar in size to normal breast epithelial cells < 7 mitoses per 10 high power fields
Score 2 10% to 75% of tumor forms glands Cells larger than normal with open vesicular nuclei, visible nucleoli, and moderate variability in size and shape 8-15 mitoses per 10 high power fields
Score 3 <10% of tumor forms glands Cells with vesicular nuclei, prominent nucleoli, marked variation in size and shap > 16 mitoses per 10 high power fields

*The mitotic count score criteria varies depending on the field diameter of the microscope used by the pathologist. The pathologist will count how many mitotic figures are seen in 10 high power fields. The criteria above use a high power field diameter of 0.52 mm.

The scores from all three categories above are added up to come up with the Overall Grade.

Overall Grade
Scores of 3, 4, or 5 Grade I
Scores of 6 or 7 Grade II
Scores of 8 or 9 Grade III

Grade I   

Breast Cancer Grade I

Histologic Grade I Invasive Ductal Carcinoma. This invasive ductal carcinoma consists of small angulated glands with fairly uniform nuclei. Grade I carcinomas tend to have be less aggressive and have a better prognosis than higher grade carcinomas. They are also more often ER positive, which is another feature associated with a more favorable prognosis.

Grade II   

Breast Cancer Grade II

Histologic Grade II Invasive Ductal Carcinoma. Portions of this invasive ductal carcinoma are forming tubular gland structures, but the remaining areas are poorly formed glands with nests of cells containing moderately atypical nuclei. Grade II carcinomas have an intermediate prognosis between the Grade I and Grade III cancers.

Grade III   

Breast Cancer Grade III

Histologic Grade III Invasive Ductal Carcinoma. This invasive ductal carcinoma consists of sheets of individual and nests cells with marked nuclear atypia and mitotic activity. Grade III carcinomas tend to behave more aggressively and have a worse prognosis that the lower grade carcinomas. They are also more often triple negative for ER, PR and HER2, which is another feature associated with aggressive behavior and a worse prognosis.