Who Is Truly High-Risk With Residual Disease in TNBC? Answers From Ki67 and TILs
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Prognostic Value of Ki67 and TILs in Residual TNBC: GBG/AGO-B Pooled Analysis, SABCS 2025 Findings
Patients with triple-negative breast cancer (TNBC) who do not achieve pathological complete response (pCR) after neoadjuvant chemotherapy have a high recurrence risk (50-70%). What does the remaining residual disease (RD) tell us? Involving more than 2,000 patients, this major analysis shows that combining tumor proliferation (Ki67) with the immune response (TILs) provides the clearest answer to who is at higher risk.
1) The Problem and Aim: Understanding Residual Disease
Failure to achieve pCR after neoadjuvant therapy indicates poor prognosis in TNBC, but not every residual tumor is the same. GBG/AGO-B aimed to create a more precise risk map by examining residual-tumor biology—proliferation through Ki67—and the host response—immune infiltration through TILs.
2) Analysis Design
German study groups GBG/AGO-B pooled data from 9 major trials, including GeparSixto, in patients who had received standard neoadjuvant therapy but had operable TNBC with residual disease (RD) (N=2,146). Cut-offs were Ki67 >20% for high proliferation and TILs <10% for low infiltration.
3) Primary Outcome: 5-Year iDFS Comparison
Disease-Free Survival (%)The Power of Combination (HR 2.4)
Combining Ki67 and TILs improves prognostic power over either alone. Patients with rapidly dividing tumors (high Ki67) and weak immune responses (low TILs) had a recurrence risk 2.4 times higher than the other group (p<0.001).
4) Other Critical Findings
| Endpoint | Increased Risk (HR) | Interpretation |
|---|---|---|
| Overall Survival (OS) | 2.1 | Death risk doubles in the high-risk group. |
| Distant Metastasis (MFS) | 2.3 | The risk of distant-organ recurrence increases substantially. |
| Effect of High TILs | - | TILs >30% improves absolute iDFS by 15%. |
| PD-L1+ Subgroup | HR 1.6 (for TILs) | TILs have a more pronounced protective value in PD-L1-positive patients. |
5) Why Does It Matter?
This analysis shows that patients without pCR do not all share the same poor outlook. Simple stratification with Ki67 and TILs identifies the "truly high-risk" group, suggesting these patients need more intensive adjuvant treatments, such as ADCs or PARP inhibitors.
Feasibility and Safety
As a biomarker analysis, it adds no toxicity. Assessing Ki67 by IHC and TILs by H&E staining uses existing pathology blocks and is inexpensive and feasible in standard laboratories.
Patient Perspective (PRO):
Questionnaires showed that reducing uncertainty and clarifying risk lowered patient anxiety (10%).
5 Frequently Asked Questions
Expert Commentary
The GBG/AGO-B analysis opens an era of "biological risk staging" in TNBC. Looking beyond residual-tumor size to its biology (Ki67) and immune microenvironment (TILs) is among the strongest, cheapest, and most accessible tools for personalized adjuvant treatment.
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