Breast cancer - grading

18 September 2023

The phrase “breast cancer” typically includes all types of cancer arising in the breast. They are classified and characterized based on:

• Microscopic (histologic) appearance of the cancer cells and surrounding tissue

  • Note that the World Health Organization (WHO) classification of breast cancer and the Table of Contents for the Breast chapter of my website show a large number of breast cancer types (carcinomas and sarcomas are types of cancer);

• molecular or protein related changes in the cancer cells affecting hormone receptors, HER2 and others (see here and the Stains section of the Table of Contents);

• its stage or extent of disease; and

• its grade or the aggressiveness of the tumor cells (the images below are from this link).

The goal of cancer grading systems is to classify breast cancers into categories with different survival statistics, which then guide treatment.

• This determination is quite complicated. It relies on clinical trials and the participation of thousands of patients to assess the reliability of these grading systems and to continually improve them over time.

• Many classification systems have been proposed for breast cancer, based on either new systems or modifications of old systems. Today, the preferred grading system is the Nottingham combined histologic grade, also called the Elston-Ellis modification of the Scarff-Bloom-Richardson grading system.

• This grading system is based on 3 features of the breast cancer viewed under the microscope, using a “representative” area of the cancer:

  • tubule and gland formation for the cancer cells;

  • nuclear pleomorphism or variations in the size and shape of the cancer cell nuclei; and

  • the number of mitotic figures in the most active areas of the cancer.

• Each feature is given a score of 1, 2 or 3 points, and the total score for the 3 features is then totaled and used to determine the cancer grade:

  • 3 - 5 points: well differentiated (grade I) - best survival statistics.

  • 6 - 7 points: moderately differentiated (grade II).

  • 8 - 9 points: poorly differentiated (grade III) - worst survival statistics.

  • Details on assigning the scores are indicated here.

Here are examples of the 3 breast cancer grades:

Well differentiated breast cancers (overall score of 3-5)

Overall score of 4 (well differentiated) based on >75% tubules (score 1), moderately enlarged nuclei compared to normal gland epithelium in the upper right) (score 2) and only rare mitotic figures (score 1). This is a relatively nonaggressive cancer with the best survival statistics.

Overall score of 5 (well differentiated) based on no tubules or glands (score 3), minimal pleomorphism (score 1) and only rare mitotic figures (score 1)

Moderately differentiated breast cancers (overall score of 6-7)

Overall score of 6 (moderately well differentiated) based on moderate (11-74%) number of tubules (score 2), moderately enlarged nuclei with small nucleoli (score 2) and identifiable mitotic figures (score 2).

Overall score of 7 (moderately well differentiated) based on no tubules (score 3), moderately enlarged nuclei with nucleoli (score 2) and identifiable mitotic figures (score 2).

Poorly differentiated breast cancers (overall score of 8-9)

Overall score of 8 (poorly differentiated) based on 11-75% tubules (score 2), markedly enlarged and pleomorphic nuclei with prominent nucleoli (score 3) and readily identifiable mitotic figures (score 3).

Overall score of 9 (poorly differentiated) based on sheets of cells (tubule score 3) with markedly enlarged and pleomorphic nuclei with prominent nucleoli (score 3) and readily identifiable mitotic figures (score 3). This is a highly aggressive cancer with the poorest survival statistics.

Other recent breast cancer essays:

My mammogram, 8 September 2023

Cancer images - inflammatory breast cancer, 27 March 2023

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