Abstract 145P
Background
Previously, it has been demonstrated that stromal tumor-infiltrating lymphocytes (sTILs) provide independent prognostic information in early-stage HER2-positive breast cancer. The aim of our study was to validate these findings by studying sTILs and outcome measures in early-stage HER2-positive breast cancer patients who were randomized to receive neoadjuvant chemotherapy with or without anthracyclines plus trastuzumab and pertuzumab in the TRAIN-2 study.
Methods
Following sTIL scoring on pre-treatment biopsies by two pathologists, the geometric mean was calculated. When the two scores differed by more than 10%, a final score was assigned after revision by one pathologist. The association between sTILs and pathological complete response (pCR) was studied using logistic regression analyses adjusted for age, hormone receptor (HR) status, clinical T-stage, clinical N-stage, tumor grade and treatment arm. Similarly, the relation between sTILs and event-free survival (EFS) was evaluated by Cox regression analyses.
Results
sTIL score was available for 389/438 patients and was associated with age, HR-status, grade and N-stage. sTIL score was associated with pCR in univariable, but not in multivariable analysis (OR 1.01, 95% CI 1.00-1.02). Similarly, sTIL score was prognostic for EFS in univariable analysis, but not in multivariable analysis (HR 0.98, 95% CI 0.97-1.00). Patients with high sTILs (above the median) and who reached pCR had excellent 5-year EFS rates (Table). Table: 145P
Stromal TILs, pathological complete response and 5-year event-free survival rates
| Group | Number of events | 5-year EFS (%) | 95% CI |
| Low sTILs, no pCR | 11/73 | 83.8 | 75.3 - 93.2 |
| High sTILs, no pCR | 8/45 | 81.7 | 71.0 - 94.1 |
| Low sTILs, pCR | 13/129 | 81.5 | 69.7 - 95.2 |
| High sTILs, pCR | 3/123 | 97.5 | 94.7 - 100 |
Conclusions
We did not observe a significant association between sTILs and pCR or EFS after adjustment for clinical variables. However, patients with pCR and high sTILs show excellent 5-year EFS rates compared to patients with no pCR or low sTILs. Early-stage HER2-positive breast cancer patients with high sTILs and pCR may be candidates for de-escalated adjuvant treatment, whereas patients with low sTILs may benefit of additional treatment.
Clinical trial identification
NCT01996267.
Editorial acknowledgement
Legal entity responsible for the study
BOOG Study Center.
Funding
Roche.
Disclosure
A.E. van Leeuwen-Stok: Financial Interests, Institutional, Funding, Roche funding for the TRAIN-2 study: Roche. H. Horlings: Financial Interests, Institutional, Funding: Roche; Non-Financial Interests, Institutional, Advisory Role: SlideScore.com. R.F. Salgado: Non-Financial Interests, Institutional, Other: Merck, Bristol Myers Squibb; Financial Interests, Institutional, Funding: Puma Biotechnology, Merck, Roche; Financial Interests, Personal, Advisory Board: Roche, Exact Sciences, Bristol Myers Squibb. G.S. Sonke: Financial Interests, Institutional, Funding: Roche, Merck, Novartis, Agendia, AstraZeneca, Seagen; Financial Interests, Institutional, Advisory Role: Seagen, Biovica. All other authors have declared no conflicts of interest.