PARPi eligibility amongst women with newly diagnosed invasive breast cancer enrolled in the GREAT universal genetic testing study.
Bibliographic record
Abstract
531 Background: Poly(ADP-ribose) polymerase inhibitors (PARPi) are approved for the treatment of BRCA-associated metastatic and high-risk early breast cancer. Recent guidelines have endorsed the use of BRCA1/2 testing for all patients with breast cancer who may be eligible for PARPi therapy, however it is unclear what proportion of patients are impacted by these recommendations. Methods: We sought to evaluate pre-test and post-test eligibility for PARPi in women aged >18 years old with a first diagnosis of stage I-IV invasive breast cancer who enrolled in a prospective, multicentered universal genetic testing study between 2019-2022. All enrolled patients underwent pre-test counselling and an obligatory primary panel of BRCA1, BRCA2, and PALB2 at the time of diagnosis. Candidacy for PARPi was determined by biologic subtype, clinical stage, pathologic stage, and/or response to neoadjuvant chemotherapy. Results: Of 1017 patients referred for the study, 805 were eligible and 729 (90.6%) consented to participate. The median age at diagnosis was 53 years (IQR, 45-62 years) and 96.2% had stage I-III disease. Overall, 32 (4.4%) patients had a germline pathogenic variant (GPV) in BRCA1/2, and 7 (1.0%) had a GPV in PALB2. Of 112 (15.4%) patients with triple negative breast cancer (TNBC), 19.6% had a GPV in BRCA1/2 or PALB2, whereas in 487 (66.8%) with ER+HER2- disease, 2.9% had a GPV (p<0.001). Among the 112 patients with TNBC, 64 (57%) were candidates for PARPi pre-genetic testing, and 12 (10.7%) remained eligible due to a GPV in BRCA1/2. Among the 487 patients with ER+HER2- breast cancer, 37 (5.1%) were candidates for PARPi pre-genetic testing, and 1 (0.2%) remained eligible due to a BRCA1 GPV identified on testing. All patients who were PARPi eligible were <65 years of age or >65 years with TNBC. Conclusions: In women with newly diagnosed invasive breast cancer, approximately 14% are candidates for PARPi prior to genetic testing, and 1.8% remain PARPi eligible due to a confirmed pathogenic variant in BRCA1/2. Consequently, genetic testing impacts systemic therapy decisions for PARPi in 10% of TNBC patients and fewer than 1% of women with ER+HER2- breast cancer. [Table: see text]
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 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 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".