<i>BRCA1/2</i> and Other Predisposition Genes in High-Risk Hormone Receptor+/Human Epidermal Growth Factor Receptor 2– Breast Cancer Treated With Endocrine Therapy With or Without Palbociclib: A Secondary PENELOPE-B Study Analysis
Bibliographic record
Abstract
PURPOSE The PENELOPE-B trial (ClinicalTrials.gov identifier: NCT01864746 ) recruited patients with hormone receptor+/human epidermal growth factor receptor 2– early breast cancer without a pathological complete response after taxane-containing neoadjuvant chemotherapy and at a high risk of relapse. Patients were randomly assigned (1:1) to receive 13 cycles of palbociclib once daily or placebo on days 1-21 in a 28-day cycle in addition to endocrine therapy (ET). PENELOPE-B did not show improved invasive disease-free survival (iDFS) after adding palbociclib to ET. This retrospective analysis investigated the impact of germline pathogenic variant (PV) status of BRCA1/2 and non- BRCA1/2 cancer predisposition genes on the outcomes of PENELOPE-B trial patients. METHODS In total, 445 patients were sampled following a case-cohort design and 442 were analyzed for germline PVs. Statistical analyses were performed for time-to-event end points (iDFS, distant disease-free survival [DDFS], and overall survival [OS]). RESULTS Of the 442 patients, 42 carried PVs in any cancer predisposition gene; 15 carried BRCA1/2 PVs. Irrespective of the treatment arms, PV status was not a prognostic factor. Regarding the treatment arms in BRCA1/2 PV carriers, numerically better 3-year outcomes were observed in the palbociclib arm (iDFS, 95%; DDFS, 95%; OS, 100%) than in the placebo arm (iDFS, 72.8%; DDFS, 72.8%; OS, 87.5%; hazard ratios palbociclib v placebo 0.349 [iDFS] and 0.562 [DDFS], not calculated for OS, too few events). In patients without BRCA1/2 PVs, the differences in 3-year outcomes were negligible. PVs in non- BRCA1/2 cancer predisposition genes did not influence the efficacy of palbociclib, although gene-specific effects could not be excluded. CONCLUSION Patients with BRCA1/2 PVs had numerically better outcomes after palbociclib. However, the number of BRCA1/2 carriers was small. Larger randomized clinical trials should consider the PV status to further evaluate whether BRCA1/2 PV carriers benefit from cyclin-dependent kinase 4 and 6 inhibitor treatment.
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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| 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".