Abstract PO2-08-07: Evaluating chemotherapy receipt and candidacy for PARP inhibitors in germline BRCA1/2 carriers with early and locally advanced breast cancer
Bibliographic record
Abstract
Abstract Introduction: While enhanced breast screening of germline BRCA1/2 carriers results in earlier stage at diagnosis, the impact of tumour biology and BRCA mutation on chemotherapy receipt in early stage disease remains understudied. Methods: We retrospectively reviewed treatment administered following a first diagnosis of BRCA1/2-associated breast cancer between 2003-2023 at our institution. Chemotherapy receipt (neoadjuvant or adjuvant) was evaluated according to tumor size, biologic subtype, and BRCA mutation. Current guidelines for PARP inhibitor use were applied to estimate the proportion of affected BRCA1/2 carriers that would be deemed eligible for targeted therapy in the future. Results: Overall, 251 affected BRCA1/2 carriers were included; 137 (54.6%) BRCA1 (median age 40 years, range 19-72) and 114 (45.4%) BRCA2 (median age 43, range, 24-80 years). Chemotherapy was administered in 70.1% of index breast cancer cases and was significantly associated with clinical tumor size (36.7% T1a-T1b, 90.9% T1c, 95.2% T2, 95.3% T3-T4, p< 0.001), nodal status (71.8% cN0 vs. 100% cN1-2, p=0.004), and biologic subtype (90.0% TNBC vs. 75.0% ER+HER2-, p=0.02). BRCA1-associated breast cancers were less likely to present with DCIS or T1 tumours (%Tis/T1; 46.7% BRCA1 vs. 70.8% BRCA2, p< 0.001) and more likely to present with triple negative disease (71.4% BRCA1 vs. 24.6% BRCA2, p< 0.001). BRCA1 carriers were more likely to require chemotherapy for index breast cancer (81.8% BRCA1 vs. 56.1% BRCA2, p< 0.001). In subgroup analysis of early stage, T1N0 disease, chemotherapy was administered in 79.0% BRCA1 and 52.2% BRCA2 patients (p=0.03). If recent guidelines incorporating biologic subtype, nodal involvement, and response to neoadjuvant chemotherapy were retrospectively applied to the cohort, 33.6% would be deemed eligible for PARP inhibitors in the adjuvant setting, including 40.9% BRCA1 and 17.5% BRCA2 affected carriers (p < 0.001). Conclusion: Chemotherapy receipt is high in BRCA-associated breast cancers including in early stage, node-negative disease. Overall, one third of affected carriers are expected to be eligible for PARP inhibitors in the adjuvant setting. Future studies exploring how this information may impact decisions around risk-reducing mastectomy are warranted. Citation Format: Stephanie Wong, Carla Apostolova, Amina Ferroum, Basmah Alhassan, Ipshita Prakash, Mark Basik, Karyne Martel, Sarkis Meterissian, David Fleiszer, Nora Wong, Talia Malagon, William Foulkes, Jean-Francois Boileau. Evaluating chemotherapy receipt and candidacy for PARP inhibitors in germline BRCA1/2 carriers with early and locally advanced breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-08-07.
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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 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".