Originally published as JCO Early Release 10.1200/JCO.2007.15.5986 on May 19 2008

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Prognostic Significance of Nottingham Histologic Grade in Invasive Breast Carcinoma

Emad A. Rakha, Maysa E. El-Sayed, Andrew H.S. Lee, Christopher W. Elston, Matthew J. Grainge, Zsolt Hodi, Roger W. Blamey, Ian O. Ellis

From the Department of Histopathology, School of Molecular Medical Sciences, Division of Epidemiology and Public Health, Department of Surgery, Nottingham University Hospitals NHS Trust, University of Nottingham, United Kingdom

Corresponding authors: Emad A. Rakha and Ian O. Ellis, MD, PhD, Molecular Medical Sciences, Department of Histopathology, University of Nottingham, Nottingham City Hospital NHS Trust, Hucknall Rd, Nottingham, NG5 1PB United Kingdom; e-mail: emadrakha{at}yahoo.com or ian.ellis{at}nottingham.ac.uk

Purpose The three strongest prognostic determinants in operable breast cancer used in routine clinical practice are lymph node (LN) stage, primary tumor size, and histologic grade. However, grade is not included in the recent revision of the TNM staging system of breast cancer as its value is questioned in certain settings.

Materials and Methods This study is based on a large and well-characterized consecutive series of operable breast cancer (2,219 cases), treated according to standard protocols in a single institution, with a long-term follow-up (median, 111 months) to assess the prognostic value of routine assessment of histologic grade using Nottingham histologic grading system.

Results Histologic grade is strongly associated with both breast cancer–specific survival (BCSS) and disease-free survival (DFS) in the whole series as well as in different subgroups based on tumor size (pT1a, pT1b, pT1c, and pT2) and LN stages (pN0 and pN1 and pN2). Differences in survival were also noted between different individual grades (1, 2, and 3). Multivariate analyses showed that histologic grade is an independent predictor of both BCSS and DFS in operable breast cancer as a whole as well as in all studied subgroups.

Conclusion Histologic grade, as assessed by the Nottingham grading system, provides a strong predictor of outcome in patients with invasive breast cancer and should be incorporated in breast cancer staging systems.

published online ahead of print at www.jco.org on May 19, 2008.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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