Understanding Your Histopathology Report: Classification of Breast Cancer

A histopathology report is a critical document providing insights into the classification of breast cancer. The examination of the biopsied tissue involves various factors that help determine the nature of the cancerous tissue. A histopathology report describes these factors. Understanding these factors may allow you to better understand your condition.

Breast cancer is known to have at least 21 different types, classified using a combination of tissue architecture and cytological (cell) features. More common types of breast cancer are ductal carcinomas in situ (DCIS), invasive ductal carcinomas of no specific type (IDC NST), invasive lobular carcinomas, and mixed invasive ductal/lobular carcinomas.

Other special types include:

• Medullary carcinoma
• Metaplastic carcinoma
• Apocrine carcinoma
• Mucinous carcinoma
• Cribriform carcinoma
• Tubular carcinoma
• Neuroendocrine tumor/carcinoma

In pathology, grading compares the appearance of the breast cancer cells to the appearance of normal breast tissue under a microscope. Pathologists look for certain features that help to predict the aggressiveness of the tumor. The most widely used grading scheme is the Nottingham grading system. It has three components.

Nuclear grade

The nuclear grade describes how different tumor cell nuclei are from normal nuclei (score 1 = similar, score 3 = very different, score 2 = intermediate).

Mitotic count

Mitotic count is a measure of how many tumor cells are dividing. An elevated mitotic count indicates that more cells are dividing, indicating a faster growth rate (score 1 = low, score 3 = high, score 2 = intermediate).

Tubule formation

Tubule formation refers to the percentage of cells with tube-shaped structures called tubules. Better differentiated tumors have more tubules (score 1 = more than 75%, score 3 = less than 10%, score 2 = 10-75%).

The scores for the three components are then added, and a combined tumor grade is reported:

• Grade 1: Well differentiated (low grade, scores 3-5)
• Grade 2: Moderately differentiated (intermediate grade, scores 6-7)
• Grade 3: Poorly differentiated (high grade, scores 8-9)

The higher the score/grade, the worse the prognosis.

The biopsied tissue will also be tested for breast cancer biomarkers, mainly estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). This is done to establish the hormone receptor and HER2 receptor status, which provide both prognostic and predictive value.

ER

Breast cancers with estrogen receptors are known as ER-positive breast cancers, while those without ER are known as ER-negative breast cancers. ER-positive breast cancers respond to anti-estrogen therapy, while ER-negative tumors do not.

PR

Breast cancers with progesterone receptors are known as PR-positive breast cancers, while those without PR are known as PR-negative breast cancers. Negativity for PR is a feature of more aggressive tumors.

HER2

Some cancerous tumors have cancer cells that make too much of a protein called HER2. These cancers are known as HER2-positive breast cancer. They respond to anti-HER2 therapy.

Receptors are cell surface proteins that receive stimulants from the surroundings of cells. In response to certain stimulants, the receptors relay signaling messages to the cells, which can affect cellular appearance, behavior, or function. Depending on the presence of these receptors, specific targeted drugs are available for treating different molecular subtypes. Cancers that do not have any of these receptors are known as triple-negative breast cancers. These can be harder to treat due to their limited treatment options.

Some other prognostic factors may also be mentioned in your histopathology report.

Lymphovascular invasion

Lymphovascular invasion (LVI) refers to the invasion of cancer to the blood vessels or lymphatics. It is an early indicator of the metastatic potential of the cancer and has been associated with a poor prognosis in breast cancer. As such, you may find this term in your histopathology report as recommended by the latest reporting protocols by the College of American Pathologists (CAP). While current guidelines do not include LVI as one of the main determinants of oncological and radiation therapy, the presence of LVI may impact you and the use of adjuvant therapy as part of your treatment plan, depending on your specific situation.

Ki-67

Ki-67 is a protein that is strongly associated with the proliferation of breast cancer cells. The Ki-67 index is used as a proliferation marker and is a known indicator of prognosis and outcome for breast cancer. However, there is significant variability in Ki-67 testing and scoring, and therefore any given result has to be interpreted with caution. In general, a Ki-67 index of 5% or less is considered low, while an index of 30% or more is considered high.

The most common staging system for breast cancer follows the American Joint Committee of Cancer (AJCC) staging manual. In the US, the 8th edition, which is the latest edition of the staging manual, is used. This edition has both clinical and pathologic staging systems for breast cancer. Pathologic staging is performed on breast cancer excisions, not on biopsies.

Patients are clinically staged according to the traditional TNM system as well as new factors. The TNM system is based on the following:

• Primary tumor size (T)

This category is based on the size of the tumor and whether or not the cancer has spread to the skin of the breast or the chest wall behind the breast.

In addition, the pathologist determines whether the tumor has been completely excised (i.e. evaluates the so-called surgical margins).

• Regional lymph node status (N)

This category looks at how many lymph nodes the cancer has spread to, if any.

• Distant metastases (M)

This category determines if the cancer has spread to a more distant part of the body like the lungs, bones, or liver.

In addition, the 8th edition staging manual looks at the tumor grade and breast biomarkers (ER, PR, HER2) mentioned above.

With all this information, breast cancer is staged from stage 0 to IV (with sub-categories for each stage based on various factors). This determines the patient’s clinical prognostic stage, which is what will be reflected in the histopathology report.

All the information obtained in the histopathology report will be used to determine the most suitable treatment strategy for you.

Learn more: Breast Cancer: Staging and Survival