Abstract P4-11-03: Androgen receptor expression is an independent marker of lower residual risk in the TACT2 trial (CRUK/05/019)
Bibliographic record
Abstract
Abstract Introduction: TACT2 (CRUK/05/019), a multicentre randomized phase III trial in patients with node +ve or high risk node -ve invasive EBC with E-CMF as control tested two hypotheses in a 2x2 factorial design, with previously presented results showing: i) no evidence of a benefit from accelerated 2-weekly epirubicin (aE) compared to standard 3-weekly epirubicin (E) (Cameron 2012); and ii) capecitabine (X) gives equivalent efficacy but preferential side-effect profile to CMF (Canney 2014). Studies suggest that Androgen receptor (AR) expression may be associated with improved outcome in early breast cancer. We performed an analysis of AR expression in TACT2 patients to test the hypothesis that AR would represent an independent predictor of residual risk following adjuvant therapy. Methods: Tumour samples were collected prospectively from 3803/4391 TACT2 patients, Tissue micro-arrays were constructed as per published guidelines and central AR, ER, PgR, HER2, Ki67, CK5/6, EGFr and BCL2 staining performed and quantified by imaged analysis for ER, PgR, HER2, Ki67 and BCL2. EGFr and CK5/6 were dichotomised by light microscopy evaluation of cores. After planned biomarker analyses had been performed, a subset of TACT2 cases for whom remaining tissue was available were analysed for AR expression. Data for 1878 cases was available for this analysis (49% of those consenting to tissue collection). AR expression was dichotomised as AR-ve (<10%) vs AR+ve (>10%). Log-rank tests were used to explore the prognostic value of AR on time to recurrence (TTR). Cox-regression models were used to test the independent prognostic value of AR in the presence of tumour size, grade, nodal status, and biological subtypes. Marker by treatment interaction terms were included in models to test the predictive value of AR for both randomised treatment comparisons. Results: 1398/1878 (74%) patients were classed as AR+ve and 480/1878 (26%) as AR-ve. The proportion of AR+ve patients differed significantly between biological subtypes (Luminal A 269/293 (92%); Luminal B 784/928 (84%); HER+ve 86/111 (77%); Basal-like 37/216 (17%); 5-marker-ve 37/93 (40%); χ2 p<0.001) 117/480 (24%) AR-ve patients had a TTR event compared with 183/1398 (13%) AR+ve patients (HR for AR-ve compared to AR+ve =2.05 95%CI 1.63-2.59; p<0.001). AR expression remained independently prognostic following adjustment for nodal status, grade, tumour size and biological subtype (HR1.68, 95%CI 1.26-2.25; p<0.001). Exploratory analysis suggested the prognostic impact of AR might be predominantly in luminal B and 5-marker-ve breast cancers; however the interaction between subtype and AR was not statistically significant. No differential treatment effect between AR subtypes was observed for either randomised treatment comparison (E/aE or CMF/X). Conclusion: AR is an independent prognostic marker for residual risk following chemotherapy in this large study which included patients with both luminal and non-luminal cancers. AR expression patterns differ between molecular subtypes of early breast cancer, with evidence suggesting the impact of AR on residual risk may also differ between subtypes. AR is currently being explored as another potential target for therapy so these data could have future clinical relevance. Citation Format: Jane Bayani, James Morden, Sunil Skaria, Peter Bliss, Robert Grieve, Adrian Harnett, Chris Bradley, Diana Ritchie, Peter Barrett-Lee, Peter Canney, David Cameron, Judith Bliss, John Bartlett. Androgen receptor expression is an independent marker of lower residual risk in the TACT2 trial (CRUK/05/019) [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 P4-11-03.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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 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".