Abstract PD3-12: Central nervous system as first site of relapse in patients with HER2 positive early breast cancer treated in the BCIRG-006 trial
Bibliographic record
Abstract
Abstract Introduction: Central Nervous System (CNS) metastases as first site of relapse is seen in 2-3% of patients with HER2+ early breast cancer (EBC) during or after treatment with adjuvant trastuzumab. Data about long-term follow-up outcomes in this population is scarce. Methodology: BCIRG-006 was designed to assess the efficacy and safety of two trastuzumab-based regimens compared to a standard (non-trastuzumab) regimen in the adjuvant treatment of HER2+ EBC. 3,222 patients were randomized to standard AC-T or two trastuzumab-based regimens (AC-TH or TCH). Ten year follow-up outcomes were previously presented; we have used this data to assess the frequency and course of CNS relapses as first site of distant recurrence. DFS and OS in these patients were estimated and compared using the Kaplan-Meier method and Log-Rank test respectively. Univariate and multivariate analyses for DFS were conducted considering patient's age, nodal status, tumor size and estrogen receptor (ER) status in the primary tumor. Results: Of the 3,222 patients randomized, 575 (17.8%) experienced a distant relapse and in 17.5% of these (n=101) CNS was the first site of recurrence. With a median follow-up of 10.3 years, the frequency of CNS relapses did not differ when comparing the trastuzumab containing arms with the control arm (OR 0.86, 95% CI: 0.56-1.33; p= 0.519). No difference was observed either between AC-TH and TCH (OR 1.14, 95% CI: 0.67-1.94; p= 0.704). There were no differences in DFS (HR 1.21, 95% CI: 0.74-1.99; p= 0.621) nor in OS (HR 0.74, 95% CI: 0.43-1.27; p= 0.377) between AC-T, AC-TH and TCH arms. Positive axillary nodes (≥4 nodes) and ER negative status at baseline remained independent risk factors for CNS relapse after univariate and multivariate analysis (HR 0.60, 95% CI: 0.8-0.95; p= 0.007 for nodal status and HR 0.56, 95% CI: 0.37-0.85; p= 0.029 for ER status). Conclusion: Among the pivotal adjuvant trastuzumab trials, BCIRG-006 is the one with the longest median FUP in which data about CNS relapses has been presented. CNS relapse in patients in this trial was an infrequent event. Its frequency and outcomes were similar across the three treatment arms. Patients with ER negative and/or ≥ 4 positive nodes are at higher risk of CNS relapse irrespective of trastuzumab therapy and may be the patient population where research efforts should be focused. BC outcomes in patients with CNS metastases per treatment arm in the BCIRG-006 trial AC-T N=1073 n(%)AC-TH N=1074 n(%)TCH N=1075 n(%)p valueFrequency of CNS relapse37 (3.44%)30 (2.79%)34 (3.16%)0.519 ^Median DFS (months; 95% CI)23.8 (13.3-30.4)19.9 (16.6-25.1)19.9 (15.0-27.2)0.621 ⫲Median OS (months; 95% CI)42.5 (28.3-62.7)53.2 (31.2-103.6)30.3 (23.4-39.0)0.377 ⫲ ^ comparing control vs. trastuzumab-containing arm using Fisher's Exact test. ⫲ comparing control vs. trastuzumab-containing arms using Log Rank test. Citation Format: Chan A, Spera G, Machado A, Fung H, Bee V, Fresco R, Slamon DJ. Central nervous system as first site of relapse in patients with HER2 positive early breast cancer treated in the BCIRG-006 trial [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 PD3-12.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".