Understanding Tumor Grade and Why It Matters

I'm not sure where to put this because it cuts across diagnoses, but there have been a lot of questions lately about tumor grade, which is thankfully getting increased attention because of the prognostic value and the clues it might provide as to treatment.

So here are some resources and definitions regarding tumor grade which I hope are helpful. Some are from this very web site.

First, with the basics:

What is TUMOR GRADE:

Tumor grade is a system used to classify cancer cells in terms of how abnormal they look under a microscope and how quickly the tumor is likely to grow and spread. Many factors are considered when determining tumor grade, including the structure and growth pattern of the cells. The specific factors used to determine tumor grade vary with each type of cancer.....Tumor grade should not be confused with the stage of a cancer. Cancer stage refers to the extent or severity of the cancer, based on factors such as the location of the primary tumor, tumor size, number of tumors, and lymph node involvement (spread of cancer into lymph nodes). (More information about staging is available in the National Cancer Institute fact sheet Cancer Staging.) ....        Source: http://www.cancer.gov/cancertopics/factsheet/detection/tumor-grade

(National Cancer Institute. Be careful when reading the rest of the page in the above link, because it refers to all cancers - not just breast.)

In the US, the Scarff-Bloom-Richardson (SBR) index has traditionally been most commonly used to calculate turmor grade. Tumor grade is associated with prognosis, but there are other prognostic yardsticks, including the Nottingham Grading System, which has been more common in Europe but is also used here with growing frequency. SBR was on my pathology report. Nottingham will appear after surgery because of the added considerations in its scaling system. Nottingham is a modification and improvement of the SBR, as I understand it, because it has better prognostic value.

The Nottingham prognostic index (NPI),10 has become widely used for the treatment of patients with breast cancer in the United Kingdom,11 and its validity has been confirmed in other independent studies.12-14 The NPI has been recognized as the only appropriately validated prognostic index in breast cancer.15 In NPI, grade and LN [MY NOTE: LN = LYMPH NODE] stage has equal weighting. However in another prognostic index (Kalmar prognostic index5) histologic grade is given a high weighting value (1.57), which is higher than that for LN stage (0.79) or size (0.31). In addition, the clinical contribution of grade has become more important as a consequence of earlier detection of breast cancer through mammographic screening and increase self awareness, which have resulted in a shift in stage distribution with lower median size of 2 cm or smaller16,17 and greater proportion of LN negative tumors at presentation.18

Histologic grading is now part of the minimum data set for breast cancer pathology reporting produced by the United Kingdom Royal College of Pathologists19 and European Commission,20 and is endorsed by the WHO21 and the College of American Pathologists.22

Source: http://jco.ascopubs.org/content/26/19/3153.full

Adjuvantonline has an interesting analysis of histologic grade. In an analysis, they conclude: 

Clearly histologic grade is a powerful but somewhat subjective parameter.  This has led to varying views on whether to use it. To some extent histological grading has been held to a higher standard than tumor size and estimates of number of positive nodes, both of which we have relatively little information about the precision of measurement, and for which there is probably more variability in measurement than generally appreciated. In the SEER data histologic grade is a very powerful prognostic parameter despite variation in its measurement. 

Note: SEER = Data on tumor registries collected by the National Cancer Institute to analyse death rates from BC)

Source: https://www.adjuvantonline.com/breasthelp0306/breastindex.html (link might not work unless you are logged in to Adjuvant!)

Finally, there are other measurements that might appear on some people's pathology reports but not others (mine included) and the validity of these characteristics is not universally accepted:

(A) pathology report may include information about the rate of cell growth - what proportion of the cancer cells within the tumor are growing and dividing to form new cancer cells. A higher percentage suggests a faster-growing, more aggressive cancer, rather than a slower, "laid back" one. Tests that can measure the rate of growth include:

• S-phase fraction: This number tells you what percentage of cells in the sample are in the process of copying their genetic information, or DNA. This S-phase, short for "synthesis phase," happens just before a cell divides into two new cells. A result of less than 6% is considered low, 6-10% intermediate, and over 10% high.
• Ki-67: Ki-67 is a protein in cells that increases as they prepare to divide into new cells. A staining process can measure the percentage of tumor cells that are positive for Ki-67. The more positive cells there are, the more quickly they are dividing and forming new cells. In breast cancer, a result of less than 10% is considered low, 10-20% borderline, and high if over 20%.

Although the S-phase fraction and Ki-67 level may provide you and your doctor with useful information, these tests are not always reliable. Experts don't yet agree on how to use the results when making treatment decisions.                                                                                Source: http://www.breastcancer.org/symptoms/diagnosis/rate_grade.jsp