Abstract P5-09-01: Nottingham prognostic index plus (NPI+): Validation of the modern clinical decision making tool in breast cancer
Bibliographic record
Abstract
Abstract Introduction Current management of breast cancer (BC) relies on risk stratification based on well-defined clinicopathologic factors. The Nottingham Prognostic Index Plus (NPI+) is based on the assessment of biological class combined with established clinicopathologic prognostic variables providing improved patient outcome stratification superior to the traditional NPI*. This study aimed to validate the NPI+ in an independent series of BC. Methods A Validation series of 469 primary early-stage BC cases treated in Edinburgh, UK were matched for size, stage and grade to cases from Nottingham, UK used to develop the NPI+ (Training series). Adjuvant therapy was similar in both series except that 143 Edinburgh cases received endocrine therapy whilst the matched Nottingham cases had no adjuvant therapy. However, there was no significant difference in 10 year BC specific survival (BCSS) between the Training and Validation series. Cases, prepared as TMAs, were immunohistochemically assessed for Cytokeratin (Ck)5/6, Ck18, EGFR, Estrogen Receptor (ER), Progesterone Receptor (PgR), HER2, HER3, HER4, Mucin 1 and p53 expression. NPI+ biological class based on the expression of the 10 biomarkers was determined. Subsequent NPI+ prognostic scores were assigned using individual algorithms for each biological class developed using the Training series incorporating clinicopathologic parameters: positive nodes (including nodal stage), tumour size, tumour grade (including mitotic index) and PgR. NPI+ biological classes, prognostic scores and prognostic groups were compared between the Validation and Training series and their role in prediction of patient outcome. A p-value of <0.01 was considered significant. Results As anticipated, there was a comparable distribution of NPI+ biological classes between Training and Validation series: Luminal A, n=143 (31%) vs n=115 (25%); Luminal N, n=99 (21%) vs n=89 (19%); Luminal B, n=75 (16%) vs n=85 (18%); Basal p53 altered, n=54 (12%) vs n=72 (15%); Basal p53 normal, n=37 (8%) vs n=53 (11%); HER2+/ER+, n=31 (7%) vs 18 (4%); HER2+/ER-, n=30 (6%) vs n=37 (8%; X2=13.792, p=0.032). BCSS was analogous between the Validation and Training series in each of the NPI+ biological classes except Luminal B (p=0.042). Similar BCSS was observed in the NPI+ Biological classes of the Training versus Validation series when taking into consideration adjuvant treatment modalities. The mean NPI+ score was similar between the Validation and Training series (2.30 vs 1.89, Pearson’s Regression p=0.079). The NPI+ prognostic groups significantly predicted patient outcome in each molecular class (BCSS, p<0.0001) in the Validation series irrespective of adjuvant treatment. Comparing the BCSS in each of the NPI+ prognostic groups demonstrated there were no significant differences between patient outcome in each of the NPI+ prognostic groups between the Validation and Training series. Conclusion This study validates the NPI+ in an independent series of primary BC confirming its’ reproducibility. The NPI+ provides improved individualised clinical decision making for breast cancer for both prediction of clinical outcome and relevant therapeutic options. Acknowledgements Funded by the MRC References *Rakha EA et al Br J Cancer. 2014 110:1688-97. Citation Format: Andrew R Green, Daniel Soria, Jacqueline Stephen, Desmond G Powe, Christopher C Nolan, Ian Kunkler, Jeremy Thomas, Gill Kerr, Wilma Jack, David Camreron, Tammy Piper, Graham R Ball, Jonathan M Garibaldi, Emad A Rakha, John MS Bartlett, Ian O Ellis. Nottingham prognostic index plus (NPI+): Validation of the modern clinical decision making tool in breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-09-01.
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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 | 0.007 | 0.025 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| 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".