Abstract PD2-04: Baseline circulating <i>ESR1</i> mutation analysis in the randomised phase III EFECT study of fulvestrant versus exemestane in advanced hormone receptor positive breast cancer
Bibliographic record
Abstract
Abstract Background. ESR1 mutations are acquired frequently in hormone receptor positive breast cancer after treatment with aromatase inhibitors (AI) in the metastatic setting. In prior analysis of the SoFEA phase III randomised trial, we demonstrated the detection of ESR1 mutations in circulating tumor DNA (ctDNA) predicted for greater benefit of fulvestrant compared to exemestane (Fribbens et al JCO 2016). Methods. The phase III EFECT study randomised 693 patients with ER+ metastatic breast cancer who had progressed on a prior non-steroidal AI, between fulvestrant loading dose and then 250mg q28 days and exemestane (Chia S, et al. J Clin Oncol 2008). Baseline serum samples were available from 227 patients in EFECT, and were analysed for the 8 most common ESR1 mutations by multiplex digital PCR. The association between baseline ESR1 status and time to progression (TTP) was analysed using Kaplan-Meier methods. Results. ESR1 mutations were successfully analysed in 98% (222/227) of patients with baseline serum samples, with ESR1 mutations detected in 23.4% (52/222) samples. Overall, detection of ESR1 mutations at baseline was associated with shorter TTP (hazard ratio [HR] 2.03, 95% CI 1.26-3.29, p=0.004). In patients with ESR1 mutation detected, TTP was 2.0 months (95%CI, 1.7-2.4) on exemestane and 3.5 months (95%CI, 1.9-5.0) on fulvestrant (HR 0.67, 95%CI 0.37-1.19, p=0.17). In patients without ESR1 mutations detected, TTP was 4.5 months (95%CI, 3.7-5.6) on exemestane and 3.7 months (95%CI, 3.3-5.2) on fulvestrant (HR 1.05, 95%CI 0.75-1.45, p=0.78). A meta-analysis of SoFEA and EFECT will be presented at the conference. Conclusions. Historical serum samples may be used for ctDNA analysis, illustrating the potential for future research of sample archives. Patients with ESR1 mutation detected in ctDNA have poor outcome when treated with exemestane, replicating prior results from SoFEA and demonstrating clinical utility for ESR1 mutation ctDNA analysis. Citation Format: Turner N, Swift C, Kilburn L, Garcia-Murillas I, Johnston S, Budzar A, Robertson J, Gradishar W, Piccart M, Schiavon G, Chia S. Baseline circulating ESR1 mutation analysis in the randomised phase III EFECT study of fulvestrant versus exemestane in advanced hormone receptor positive breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD2-04.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.004 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 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".