Histologic Grades of Breast Cancer: Helping Determine a Patient's Outcome

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• What is a histologic grade system?
• Summary of Histologic Grades of Breast Cancer
• Hormone Receptor Status
• DNA Cytometry
• Additional References and Resources

What is a Histologic Grade System?

Histology is the study of tissues, including cellular structure and function. Pathologists (physicians who conduct laboratory studies of tissues and cells) often assign a histologic grade to a patient’s cancerous breast tumor to identify the type of tumor present and help determine the patient’s prognosis (projected outcome). The Scarff-Bloom-Richardson system is the most common type of cancer grade system used today. To determine a tumor’s histologic grade, pathologists examine the breast cancer cells and their patterns under a microscope. A sample of breast cells may be taken from a breast biopsy,  lumpectomy  or mastectomy. 

Pathologists closely observe three features when determining a cancer’s grade: the frequency of cell mitosis (rate of cell division), tubule formation (percentage of cancer composed of tubular structures), and nuclear pleomorphism (change in cell size and uniformity). Each of these features is assigned a score ranging from 1 to 3 (1 indicating slower cell growth and 3 indicating faster cell growth). The scores of each of the cells’ features are then added together for a final sum that will range between 3 to 9.

Courtesy of the American Medical Association

Summary of Histologic Grades of Breast Cancer

A tumor with a final sum of 3, 4, or 5 is considered a Grade 1 tumor (well-differentiated). A sum of 6 or 7 is considered a Grade 2 tumor (moderately-differentiated), and a sum of 8 or 9 is a Grade 3 tumor (poorly-differentiated).

*Scarff-Bloom-Richardson grade system

Pathologists also look for necrosis (areas of degenerating cancer cells) when determining a tumor’s grade. Cancers with a high grade, necrosis, cancers close to the surrounding margin of breast tissue of a lumpectomy sample, or large areas of DCIS are more likely to recur after breast cancer treatment than other breast cancers.⁽¹⁾

Hormone Receptor Status

Physicians often examine hormone receptors in breast cancer cells at the time of biopsy or breast surgery to determine whether estrogen receptors (ER-positive) or progesterone receptors (PR-positive) are present. Patients whose cancers have ER or PR-positive receptors tend to have a better prognosis than patients whose cancers do not have these receptors. Cancers with ER or PR-positive receptors are also much more likely to respond to chemotherapy or hormone treatment.

Breast cancer cells that express ER-positive receptors in their nuclei also tend to respond better to hormonal manipulation. For example, the drug tamoxifen is used to block the female hormone estrogen from estrogen receptors, thus slowing the growth and reproduction of cancerous cells. Researchers know less about PR-positive receptors but have noticed that cells that contain ER-positive receptors often contain PR-positive receptors too. If a cell contains a PR-positive receptor but no ER-positive receptors, a patient’s prognosis may be worsened.

HER2 (human epidermal growth factor receptor 2), a protein receptor found on the surface of cells, is a key component in regulating cell growth. When the HER2 gene (sometimes written HER2/neu) is altered, extra HER2 receptors may be produced. This over-expression of HER2 causes increased cell growth and reproduction, often resulting in more aggressive tumor cells. HER2 protein over-expression affects 25% to 30% of breast cancer patients. A new drug, herceptin, has recently been approved by the U.S. Food and Drug Administration (FDA) to treat women with metastatic breast cancer who over-express HER2. Metastatic breast cancer is cancer that has spread past the breast and underarm lymph nodes.

Physicians may test tumor tissue for HER2 over-expression at the time of breast biopsy or surgery. Testing may also be done on stored tumor tissue from previous biopsy. To test for HER2 over-expression, the tumor tissue will be stained by a specific solution. A pathologist will then examine the tissue, checking for highlighted areas where high levels of over-expression are present. Depending on the level of staining, the tumor tissue sample may be classified as HER2 positive.

It is estimated that 200,000 HER2 diagnostic tests are performed each year. Women are encouraged to be tested for HER2 over-expression at the time of breast cancer diagnosis since results of the test may help determine a course of treatment.

DNA Cytometry

Cytometry is the process of counting and measuring a patient’s cells. DNA cytometry involves measuring a breast tumor’s DNA to help predict the tumor’s aggressiveness. Flow cytometry is one type of DNA cytometry in which lasers and computers are used to measure the amount of DNA in cancer cells suspended in liquid as they flow past a laser beam. A second type of DNA cytometry, image cytometry, involves using computers to analyze digital images of the cells from a microscope slide. Both flow cytometry and image cytometry measure the DNA ploidy (amount of DNA) of cancer cells. Ploidy is a marker that helps predict how quickly a cancer is likely to spread. Cancers with the same amount of DNA as normal cells are called diploid and those cancers with either more or less than that amount are called aneuploid. About two-thirds of breast cancers are aneuploid.⁽¹⁾ Several studies have shown that aneuploid cancers tend to be more aggressive than normal cancers.

Flow cytometry can also measure a tumor’s S-phase (the percentage of cells in a sample that are in the synthesis stage of cell division). Many cells in the S-phase indicate that the breast tissue is growing fast and that the cancer is likely to be more aggressive than normal cancers. Image cytometry can also estimate the growth rate of a cancer when combined with special antibody tests of the breast tissue.

Additional Resources and References

• (1) The American Cancer Society provides detailed information on histologic grades at http://www.cancer.org/.
• To learn more about HER2 and how the drug herceptin helps treat breast cancer patients who over-express the HER2 gene, please visit http://www.imaginis.com/breasthealth/herceptin.asp

Updated: October 18, 2009