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Summary



Histological Grading of Breast Cancer

Within the last decade, histologic grading has become widely accepted as a powerful indicator of prognosis in breast cancer. The majority of tumor grading systems currently employed for breast cancer combine nuclear grade, tubule formation and mitotic rate. In general, each element is given a score of 1 to 3 (1 being the best and 3 the worst) and the score of all three components are added together to give the "grade" (1-4). The lowest possible score (1+1+1=3) is given to well differentiated tumors that all form tubules and have a low mitotic rate (<10/10 HPF). The highest possible score is 9 (3+3+3=9). The exact criteria for each component differ in each system and the systems are evolving as more detailed data becomes available (5-7). Some studies even suggest that mitotic rate alone can be as predictive as the grading systems(8).

Until recently, the most common grading systems used in the United States were the original Scarff-Bloom-Richardson (SBR) system as described above and the Black method which emphasizes nuclear grading and excludes consideration of tubules as a criteria (9). In Europe, the Elston-Ellis modification of the SBR grading system (Nottingham grading system) is preferred and is becoming increasingly popular in the US (7). This modification provides somewhat more objective criteria for the three component elements of grading and specifically addresses mitosis counting in a more rigorous fashion (4). For example hyperchromatic nuclei and apoptotic cells which are counted in the original SBR system are excluded in the Elston-Ellis modification and the area being assessed is specifically defined in square millimeters. These modifications have enhanced reproducibility of grading among pathologists and to a considerable extent have fostered acceptance of grading by clinicians (7,10-20). An excellent historical discussion of grading systems can be found in Elston and Ellis (17).

Criteria for grading are an active area of investigation particularly in regards to defining more objective criteria for assessing nuclear grade and we should expect image analysis to greatly contribute to this area in the future. The beginner is encouraged to consult their local pathologist to determine which system is used in their institution. The examples provided here, by Dr. Hanne Jensen, illustrate how the Nottingham Grading System can be used to grade a tumor.

 

NOTTINGHAM GRADING SYSTEM
   


1.

Scarff, R.W. and Torloni H. (1968) Histological typing of breast tumors., International histological classification of tumours, no. 2. Vol. 2. World Health Organization, Geneva, pp. 13-20.

2. Bloom, H.J. and Richardson W.W. (1957) Histological grading and prognosis in breast cancer. Br. J. Cancer, 11, 359-377.
3.

Elston, C.W. (1984) The assessment of histological differentiation in breast cancer. Aust N Z J Surg, 54, 11-5.

4.

Elston, C.W. and Ellis I.O. (1991) Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology, 19, 403-10.

5.

Dalton, L.W., Pinder S.E., Elston C.E., Ellis I.O., Page D.L., Dupont W.D. and Blamey R.W. (2000) Histologic grading of breast cancer: linkage of patient outcome with level of pathologist agreement [In Process Citation]. Mod Pathol, 13, 730-5.

6.

Le Doussal, V., Tubiana-Hulin M., Friedman S., Hacene K., Spyratos F. and Brunet M. (1989) Prognostic value of histologic grade nuclear components of Scarff-Bloom-Richardson (SBR). An improved score modification based on a multivariate analysis of 1262 invasive ductal breast carcinomas. Cancer, 64, 1914-21.

7.

Simpson, J.F., Gray R., Dressler L.G., Cobau C.D., Falkson C.I., Gilchrist K.W., Pandya K.J., Page D.L. and Robert N.J. (2000) Prognostic value of histologic grade and proliferative activity in axillary node-positive breast cancer: results from the Eastern Cooperative Oncology Group Companion Study, EST 4189. J Clin Oncol, 18, 2059-69.

8.

Clayton, F. (1991) Pathologic correlates of survival in 378 lymph node-negative infiltrating ductal breast carcinomas. Mitotic count is the best single predictor. Cancer, 68, 1309-17.

9.

Black, M.M., Opler S.R. and Speer F.D. (1955) Survival in breast cancer in relation to structure of the primary tumor and regional lumph nodes. Surg. Gynecol. Obster., 100, 543-551.

10.

Balslev, I., Axelsson C.K., Zedeler K., Rasmussen B.B., Carstensen B. and Mouridsen H.T. (1994) The Nottingham Prognostic Index applied to 9,149 patients from the studies of the Danish Breast Cancer Cooperative Group (DBCG). Breast Cancer Res Treat, 32, 281-90.

11.

Carriaga, M.T. and Henson D.E. (1995) The histologic grading of cancer. Cancer, 75, 406-21.

12.

Charpin, C., Bacquie N., Bouvier C., Devictor B., Boulat J., Andrac L., Lavaut M.N., Allasia C. and Piana L. (1995) Comparison of the prognostic significance of current and modified histological grades in breast carcinomas. Anticancer Res, 15, 2611-7.

13.

Contesso, G., Mouriesse H., Friedman S., Genin J., Sarrazin D. and Rouesse J. (1987) The importance of histologic grade in long-term prognosis of breast cancer: a study of 1,010 patients, uniformly treated at the Institut Gustave-Roussy. J Clin Oncol, 5, 1378-86.

14. Dalton, L.W., Page D.L. and Dupont W.D. (1994) Histologic grading of breast carcinoma. A reproducibility study. Cancer, 73, 2765-70.
15.

Davis, B.W., Gelber R.D., Goldhirsch A., Hartmann W.H., Locher G.W., Reed R., Golouh R., Save-Soderbergh J., Holloway L., Russell I. and et al. (1986) Prognostic significance of tumor grade in clinical trials of adjuvant therapy for breast cancer with axillary lymph node metastasis. Cancer, 58, 2662-70.

16.

Ellis, I.O., Galea M., Broughton N., Locker A., Blamey R.W. and Elston C.W. (1992) Pathological prognostic factors in breast cancer. II. Histological type. Relationship with survival in a large study with long-term follow-up. Histopathology, 20, 479-89.

17.

Elston, C.W. and Ellis I.O. (1998.) Assessment of histological grade. In Elston, C.W. and Ellis, I.O. (eds), The breast. Vol. 13. Churchill Livingstone, Edinburgh ; New York, pp. 356-384.

18.

Elston, C.W., Ellis I.O. and Pinder S.E. (1999) Pathological prognostic factors in breast cancer. Crit Rev Oncol Hematol, 31, 209-23.

19.

Genestie, C., Zafrani B., Asselain B., Fourquet A., Rozan S., Validire P., Vincent-Salomon A. and Sastre-Garau X. (1998) Comparison of the prognostic value of Scarff-Bloom-Richardson and Nottingham histological grades in a series of 825 cases of breast cancer: major importance of the mitotic count as a component of both grading systems. Anticancer Res, 18, 571-6.

20. Pinder, S.E., Murray S., Ellis I.O., Trihia H., Elston C.W., Gelber R.D., Goldhirsch A., Lindtner J., Cortes-Funes H., Simoncini E., Byrne M.J., Golouh R., Rudenstam C.M., Castiglione-Gertsch M. and Gusterson B.A. (1998) The importance of the histologic grade of invasive breast carcinoma and response to chemotherapy. Cancer, 83, 1529-39.

 

Robert D. Cardiff and Roy A. Jensen




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Summary