Abstract P6-09-20: Clinical utility of PgR with various cutpoints using 3 commercial assays relative to 15yr survival
Bibliographic record
Abstract
Abstract Introduction: Hormone receptors ER and PgR are routinely assessed by pathologists using immunohistochemical (IHC) assays to guide treatment decisions. Patients who are hormone receptor positive are offered hormonal therapy, such as tamoxifen, which improves survival. Although both ER and PgR are evaluated, ER is primarily utilized for patient management as the clinical utility of PgR has not been clearly established according to CAP/ASCO guidelines. Notably, a meta-analysis by the Early Breast Cancer Trialists' Collaborative Group reported that PgR status was not significantly predictive of response to adjuvant tamoxifen, suggesting that PgR may not have a role in breast cancer management. More recently, the level of PgR expression has been hypothesized to be important in predicting response to endocrine therapy, where high PgR levels are more indicative of estrogen-dependent tumors, and thus more sensitive to hormonal treatment. In this study, we evaluate PgR expression using the current cut-point (Allred>2), as well as an optimized cut-point (Allred>5 to identify PgR high tumors), with regards to 15yr disease-free survival (DFS) and disease-specific overall survival (DSOS) using three commercially available ready-to-use (RTU) IHC assays from Dako, Leica and Ventana in an ER+ cohort. Methods: The Calgary tamoxifen breast cancer cohort (Calgary cohort) is a TMA series that includes 532 patients diagnosed with primary breast cancer (1985-2000) who received tamoxifen treatment regardless of hormone receptor status. All RTU assays followed vendor recommended protocols. Specific details regarding the cohort and IHC assays have been previously described (Kornaga et al. Mod Path 2016). All analyses were performed using Stata 12, and multivariate models were adjusted for age, grade, size, lymph node and HER2 status. ER status was defined by the corresponding vendor specific IHC assay. Results: Multivariate models looking at DFS are presented in Table 1. None of the assays were significant when the clinical cut-point was used; however, when the optimized cut-point was investigated, all assays found high expression of PgR was significantly associated with improved DFS. Table 2 presents the multivariate models looking at DSOS. Similarly, PgR was not found to be associated with improved DSOS using the current cut-point. When the optimized cut-point was examined, Dako and Leica assays were significantly associated with improved DSOS: The Ventana assay did not reach significance. Table 1 PgR15YR DFS CutpointHR95% CIp-valueDako>20.830.40-1.730.624Dako>50.560.35-0.910.020Leica>21.130.45-2.830.792Leica>50.520.30-0.890.017Ventana>20.730.32-1.670.460Ventana>50.570.34-0.970.037 Table 2 PgR15YR DSOS CutpointHR95% CIp-valueDako>20.740.33-1.650.464Dako>50.550.32-0.950.031Leica>20.880.35-2.220.780Leica>50.440.24-0.790.006Ventana>20.590.25-1.370.218Ventana>50.630.35-1.150.134 Conclusions: High PgR expression (Allred>5) is associated with improved 15yr DFS and DSOS in a tamoxifen-treated cohort, where PgR positivity defined using current guidelines is not associated with improved DFS or DSOS. Additionally, differences were noted between the vendor RTU assays with regards to DSOS. Citation Format: Kornaga EN, Paterson AHG, Feng X, Morris DG, Magliocco AM, Klimowicz AC. Clinical utility of PgR with various cutpoints using 3 commercial assays relative to 15yr survival [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-20.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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 teacher head, 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".