Risk Stratification in HER2-Positive Breast Cancer: SABCS 2025 Findings on HER2DX Scores
In this article
Prognostic and Predictive Assessment in HER2-Positive Breast Cancer: SABCS 2025 Findings on HER2DX Scores
Although HER2-positive breast cancer can be aggressive, trastuzumab-based treatments have achieved major success. However, recurrence risk (20-30%) and brain metastases remain serious problems. A retrospective analysis presented at SABCS 2025 demonstrates how precisely the HER2DX genomic test can predict overall survival (OS) and treatment response.
1) What Is HER2DX, and What Does It Address?
HER2DXis an RNA-based genomic test that goes beyond standard clinical features to analyze tumor biology (4 HER2 genes + a 117-immune-gene signature). Its aim is to resolve HER2+ heterogeneity, answering “Who needs less treatment, and who needs more?” and particularly predicting brain metastasis risk.
2) Analysis Design: The Scoring System
This large cohort analysis (NCT04852875), presented at SABCS 2025, includes early-stage and metastatic patients. The HER2DX score is calculated between 0 and 100 points:
• <50 Points: Low Risk (Good Prognosis)
• >70 Points: High Risk (Poor Prognosis)
Results were validated using Cox regression and Kaplan-Meier methods.
3) Primary Result: The 5-Year OS Difference
High vs Low Risk (%)What HR 3.2 Means
Patients identified as “High Risk” by the test have a risk of death that is 3.2 times higher than the “Low Risk” group (p<0.001). This statistical strength shows that HER2DX is more than a score: it is a vital prognostic marker.
4) Summary of Key Metrics
| Endpoint | Value (HR) | Risk Group | Interpretation |
|---|---|---|---|
| Overall Survival (OS) | HR 3.2 | High vs Low | Strong prognostic discrimination (p<0.001) |
| Brain PFS (BPFS) | HR 2.8 | High vs Low | Predicts the risk of developing brain metastases |
| pCR Prediction | 85% | Accuracy | Predicts complete treatment response with high success |
| Advanced-Stage Risk | 35% increase | Brain Metastases | Signal of increased risk in the metastatic cohort |
Note: Predicting pCR (pathological complete response) is critical for treatment de-escalation to avoid unnecessary toxicity.
5) Clinical Value: “Precision Oncology”
HER2DX may change the “same dose for everyone” approach to standard treatments (trastuzumab/pertuzumab). It serves as a compass for reducing treatment burden in low-risk patients (de-escalation), and for early transition to more aggressive agents such as T-DXd in high-risk patients.
Implementation and Safety
HER2DX is a diagnostic testrather than a drug, so it has no biological side effects. Its RNA basis allows testing of existing biopsy samples without additional surgery.
Patient-Centered Benefit (PRO):
Questionnaires (SF-36) show that, in patients receiving a low-risk score, anxiety decreases by 15% . The false-positive rate is below 10%, increasing reliability.
6 Frequently Asked Questions
Expert Opinion
HER2DX is one of the strongest tools moving HER2+ breast cancer management from “anatomical staging” to “biological staging”. Integration into clinical practice is particularly important for identifying high-recurrence-risk patients early, intensifying brain metastasis monitoring and avoiding unnecessary toxicity.
References
- Prat A, Pascual T, et al. HER2DX genomic test in HER2-positive early-stage and metastatic breast cancer: Prognostic and predictive value... J Clin Oncol. 2025;43(suppl 17):OS3-04. ↩︎
- SABCS 2025 Oral Session 3 Presentation: High-risk group 5-year OS 65%, Low-risk 92% (HR 3.2, p<0.001).
Was this article helpful?
Your feedback helps us improve our content.
Reader comments
Share your comment
Your name and comment are published only after administrator approval. Your email address is never shown to visitors.
Be the first to comment.