Abstract P1-06-04: Simplified histological grading of breast carcinoma – potential for improved concordance and consistency in breast cancer grading?
Bibliographic record
Abstract
Abstract 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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.027 | 0.051 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".