Abstract PD3-03: Circulating tumor DNA in HER2 amplified breast cancer: A translational research substudy of the NeoALTTO phase 3 trial
Bibliographic record
Abstract
Abstract Purpose. To evaluate whether circulating tumor DNA (ctDNA) was associated with response to neoadjuvant anti-HER2 targeted therapies (NAT) in patients enrolled in the Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization (NeoALTTO) trial (BIG 1-06). Methods. Cell-free DNA from plasma collected before NAT, at week 2 and before surgery were processed using patient-specific droplet digital polymerase chain reaction (ddPCR) assays for the detection of PIK3CA and p53 mutations. These mutations had been previously detected in baseline primary tumor biopsy samples using mass spectrometry-based genotyping, exome or RNA sequencing. Chi-square test was used to evaluate differences in ctDNA detection according to the NeoALTTO stratification factors: clinical tumor size (T2 vs T3/4), clinical nodal status (N0/1 vs N2), Hormone Receptor status, HR (positive vs negative) and type of breast surgery planned (conservative vs mastectomy). Associations between ctDNA detection and either pathological complete response (pCR) or event-free survival (EFS) after adjustment for the NeoALTTO stratification factors were investigated using logistic and Cox regression models, respectively. Results. A total of 69 of 455 (15.2%) patients enrolled in the NeoALTTO trial had either PIK3CA (55 patients) or p53 (14 patients) mutations detected in the baseline tumor samples and at least one plasma sample with evaluable ctDNA results. Out of the 69 patients, 36 (52.2%) had HR-negative disease, 45 (65.2%) had T2 tumors, 55 (79.7%) N0/1 disease, 50 (72.5%) were candidates for mastectomy and 27 (39.1%) received trastuzumab and lapatinib in combination. ctDNA before NAT, at week 2 and before surgery was detected in 29 (42%) of 69, in 13 of 64 patients (20.3%) and in 4 of 59 (6.7%) patients analyzed, respectively. There was no significant difference in ctDNA detection before NAT according to HR status, clinical tumor size, nodal status or type of planned breast surgery. After adjustment for the NeoALTTO stratification factors, ctDNA detection before NAT was associated with decreased odds of achieving pCR, (odds ratio, OR 0.16, 95% CI 0.04-0.71, p=0.016), but not with EFS (Hazard Ratio 1.32, 95%CI 0.74-2.37, p=0.345). Neither ctDNA detection at week 2 nor before surgery was significantly associated with either pCR or EFS but these analyses were underpowered. Conclusion In patients with HER2-amplified tumors and either PIK3CA or p53 mutations, detection of ctDNA before neoadjuvant anti-HER2 targeted therapies is associated with decreased probability of pCR. Citation Format: Ignatiadis M, Silva MJ, Campbell C, Bradbury I, de Azambuja E, Maetens M, Fumagalli D, Rodrik-Outmezguine V, Di Cosimo S, Rosa D, Chia S, Wardley A, Ueno T, Janni W, Huober J, Baselga J, Piccart M, Sotiriou C, Loi S, Rothé F, Dawson S. Circulating tumor DNA in HER2 amplified breast cancer: A translational research substudy of the NeoALTTO phase 3 trial [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 PD3-03.
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 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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".