Abstract P1-06-04: Simplified histological grading of breast carcinoma – potential for improved concordance and consistency in breast cancer grading?
Authors: Bartlett JMS , Thomas J , Mallon E , Piper T , Bayani J , Hasenburg A , Kieback DG , Markopoulos C , Dirix L , Seynaeve C , van de Velde CJH , Rea DW 
Published: February 2018

Histological grade remains an independent predictor of outcome for invasive breast cancer. The internationally accepted standard grading system is the Elston and Ellis grading system based on a local hospital (Nottingham) cohort treated between 1951-1973. Histological grade, with nodal status, tumour size and receptor measurements (ER, PgR, HER2) give important information even in the context of current molecular testing for breast cancer. In 2009 we proposed a simplified approach to the EE system based on evidence from another hospital series (Thomas et al Histopathology 2009 DOI 10.1111/j.1365-2559.2009.03429.x). Here we report a second validation of this approach using a large phase III clinical trial cohort the Tamoxifen Exemestane Adjuvant multicentre Trial.

A single pathologist (EM) regraded over 4200 cases using a single H&E slide from the TEAM pathology study. Individual scores (1-3) were provided for tubule formation, nuclear pleomorphism and mitotic count and summed to provide the EE score (3-9) resulting in a final grade of 1, 2 or 3 for each case. As previously reported the Simplified Binary Scoring system (SBS) reorganizes this data such that each component is given a score of 1 or 2 with a sum ranging from 3-6. In the current analysis we compared the impact of this revised grading system on patient outcome.

Of 4264 centrally regraded tumours in the TEAM pathology cohort, EE scores for tubular formation were 1 in 102 cases (2.4%), 2 in 503 cases (11.8%) and 3 in 3659 (85.8%). For nuclear pleomorphism only 2 cases were EE score 1 (0.05%), 3117 were score 2 (73.1%) and 1146 score 3 (26.9%). For Mitotic count 3423 (80.3%) were scored 1, 707 (16.6%) scored 2 and 134 scored 3 using the EE system. As previously observed, most/all EE categories could be captured using a simple binary system (SBS, see Table 1).

Table 1 EE Grade  SBS SCORE12335460043239705068217600618 GG Score  EE GradeLowHigh 13327819.02%21377132248.98%35751790.07% GG Score  SBS SCORELowHigh 33508419.35%4120284741.34%515947474.88%65751289.98%

In a comparison between conventional grading and molecular (using a Genomic-Grade signature) we observed the predicted equal split of EE Grade 2 cases into GG high/versus low. For the SBS score the higher scores were enriched for GG High cases.

We show a novel grading system can provides a potentially simple and more reproducible approach to immunohistochemical grading. Comparisons with molecular grading approaches may suggest improved concordance between novel grading approaches and molecular systems. Further comparisons with outcome and molecular signatures will be presented.

Citation Format: Bartlett JMS, Thomas J, Mallon E, Piper T, Bayani J, Hasenburg A, Kieback DG, Markopoulos C, Dirix L, Seynaeve C, van de Velde CJH, Rea DW. Simplified histological grading of breast carcinoma – potential for improved concordance and consistency in breast cancer grading? [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-06-04.