Breast Cancer Grades and What They Mean

Unpacking the different breast cancer grades, how they are determined, and how they inform treatment

A breast cancer diagnosis can be overwhelming, particularly as you and your care team navigate the best treatment plan. Part of this process involves obtaining a breast biopsy and understanding all the details in the resulting pathology report. Here, we discuss one key piece of information within your pathology report—tumor grade—and what information can be gleaned from this classification.

Breast cancer grade is a measure of how the cancer might behave. It helps guide treatment by capturing important biological information specific to the tumor and potentially indicating its long-term outcome.  

Understanding what each breast cancer grade means can help add clarity to your pathology report, empowering you to ask more informed questions and make more confident choices about your treatment plan.

Read on to learn what each breast cancer grade is, how they differ from cancer stages, how grade is determined, and how this information can help shape a care plan.

What is a breast cancer grade?

Breast cancer grade is a measure of how closely the cancer cells resemble normal cells under a microscope. Tumor grade is not directly used to determine breast cancer stage, which describes how far the cancer has spread in the body. But the grade does provide crucial cellular-level information used to personalize treatment plans. Therefore, breast cancer stages and grades are not the same thing.

When a breast cancer sample is taken via a biopsy, the pathologist, a physician trained to identify and diagnose disease by examining cells and tissue samples, will look for certain cellular characteristics. These can help predict how likely the cancer will grow and spread. They include:

• The arrangement and uniformity of the cells in relation to each other
• How closely the tumor tissue resembles normal, organized breast tissue architecture, including the formation of tiny tube-shaped structures, called tubules. In healthy breast tissue, tubules transport breast milk from glands to nipples.
• How much a tumor cell and its nucleus, the compartment containing the cell’s DNA, look like a normal breast cell and nucleus (nuclear grade)
• How many of the cancer cells are multiplying i.e., the number of mitoses/cellular divisions visible in a defined area under the microscope, also called mitotic count

Together, these features determine the cancer’s grade, which helps predict a patient’s outlook and guide treatment decisions.

How are breast cancer grades categorized?

Breast cancer grades can be expressed in different ways. Cancer cells can be described as well-differentiated, moderately differentiated, or poorly differentiated, depending on how the cellular features appear under the microscope.

• Well-differentiated carcinomas are made up of relatively normal-looking cells that do not appear to be growing rapidly. These tend to grow slowly and have a better prognosis.
• Moderately differentiated carcinomas exhibit a mix of normal and abnormal cell characteristics, falling between well-differentiated and poorly differentiated carcinomas.
• Poorly differentiated carcinomas contain cells that look most different from normal cells. They tend to grow and spread faster and are associated with a worse prognosis.

Another way to express grade is a numerical assignment via the Nottingham Histologic Score system (also called the Elston-Ellis modification of Scarff-Bloom-Richardson grading system). A pathologist will observe the extent of tubular formation within the tissue sample, the nuclear grade, and the mitotic count and assign numerical scores from one to three in each of these three categories.

The tumor category score is derived from the three areas as follows: more tubule-like formations receive a lower score; more cells and nuclei that appear abnormal or large receive a higher score; and the more mitoses observed in the tumor cells the higher the score.

Those scores are then summed to designate the grade:

• Grade 1 breast cancer is assigned if the numbers add up to three, four or five. 
• Grade 2 breast cancer is assigned if they add up to six or seven. 
• Grade 3 breast cancer is assigned if they add up to eight or nine. 

Grade 1 breast cancer

Grade 1 tumor cells appear similar to normal breast cells and have small glands with uniform cellular nuclei. They tend to be less aggressive and grow more slowly than higher grade tumors and are more likely to be estrogen receptor (ER)–positive, another feature associated with a more favorable prognosis. Grade 1 breast cancer is often called low-grade or well-differentiated cancer.

Grade 2 breast cancer

Portions of this tissue sample form normal looking tubular structures, but some areas have poorly formed or no tubules. Cells contain moderately atypical nuclei. Grade 2 breast cancer is often called intermediate grade cancer or moderately differentiated cancer and have intermediate features and prognosis between grade 1 and grade 3 cancers.

Grade 3 breast cancer

Grade 3 breast cancers appear very different from normal cells under the microscope. They have a marked atypical and non-uniform appearance of the cells and their nuclei, and have high mitotic activity. Grade 3 tumors tend to behave more aggressively and are associated with worse prognosis than lower grade tumors. They are more often triple-negative breast cancers, or cancers that lack hormone receptors (estrogen and progesterone) and human epidermal growth factor 2 (HER2).

Ongoing research, much of it supported by BCRF, is improving outcomes for breast cancer with the most aggressive biological profiles.

Ductal carcinoma in situ grades

Ductal carcinoma in situ (DCIS), or stage 0 breast cancer, is the earliest stage of breast cancer. It is cancer (carcinoma) that starts in the cells lining the milk ducts but remains in the area where it originates (in situ). It does not always progress to invasive breast cancer (cancer that has spread into surrounding breast tissue beyond the ducts) but is considered a precursor.

A system similar to that used for invasive breast cancer is used to grade DCIS:

• Low grade or nuclear grade 1 DCIS has low mitotic activity, tends to grow slowly, and is less likely to return after surgical removal. Low grade DCIS cells tend to be positive for both estrogen and progesterone receptors, which means hormone therapy can be used to help lower the risk of DCIS returning after treatment.
• Intermediate grade or nuclear grade 2 DCIS has intermediate mitotic rate, grows more quickly, and is more likely to return after surgery than grade 1.
• High grade or nuclear grade 3 DCIS has a high mitotic rate, grows the fastest of the grades, and is most likely to come back after surgical removal. These cells are more likely to be negative for estrogen and progesterone receptors. High grade DCIS is more likely to become invasive breast cancer.

Comedo necrosis refers to a high-grade DCIS that contains dead or dying cells. In this instance, cells rapidly proliferate and outgrow their blood supply, leading to cell death in the center of the tumor. Comedo necrosis is associated with a higher risk of invasive breast cancer.

How breast cancer grade fits into the bigger picture

Tumor grade is more than just a line on a pathology report. It provides one of the clearest lenses through which you, with your care team’s guidance, can glimpse the cancer’s biology, behavior, and likelihood of progression so you can plan your next steps.

But while grade is important, it’s just one part of the big picture. Other factors like tumor size, how far the cancer has spread to other locations within the body, hormone receptor status (ER and PR), HER2 status, and molecular subtype all play essential roles in shaping a treatment plan and predicting outcomes.

Understanding what distinguishes slow-growing grade 1 breast cancer from more aggressive grade 3 breast cancer—or how high‑grade DCIS may require more vigilance—can help you turn the data in your pathology report into actionable knowledge.

Thanks to continued progress in breast cancer research and advances in personalized care, even high-grade cancers are being treated more precisely and effectively than ever before.