Abstract 158P
Background
We investigated the impact of baseline tumor infiltrating lymphocytes (TIL) density and TIL composition along with clinicopathological factors on pathologic complete response (pCR) rate in patients treated with standard neoadjuvant chemotherapy ± targeted therapy for early breast cancer.
Methods
A prospective non-interventional study in luminal B, HER2+ and triple- negative breast cancer was performed. In addition to classical determinants (molecular subtype, grade and clinical stage), TIL density based on diagnostic standard (low 1-15%, medium 16-49% and high: ≥50%) and TIL composition (CD8 and CXCL13 as anti-tumor factors, and PD-1 and FOXP3 as proinflammatory factors) were evaluated by HE/immunohistochemistry. Cut-offs for high TIL components were medians: ≥40% for CD8, ≥3% for FOXP3, ≥1% for PD1 and ≥1% for CXCL13. To compare pCR and non-pCR groups, chi-square or two tailed unpaired t-test were used. Binary logistic regression was performed to find independent factors associated with pCR.
Results
Of 268 patients entered study 171 were eligible. Molecular subtypes were: 53% Luminal B-like, 9% HER2+, 19% HER2+ luminal and 19% triple negative. Median age was 48.4 (range 26-80) years. Tumor characteristics were: 15% cT1, 66% cT2, 19% cT3, 73% cN+, 73% grade III, 91% Ki67≥20%, 24% medium TIL, 14% high TIL, 58% high CD8, 75% high CXCL13, 63% high PD-1, 61% high FOXP3. High CD8 and/or CXCL13 had 84% and high PD1 and/or FOXP3 had 76% of pts. pCR rate in breast, axilla, and total pCR were: 35%, 56%, and 32%, resp. Independent factors associated with total pCR were: cN-, HER2+ and HER2+ luminal subtypes, high TIL, GIII and high PD-1 and/or FOXP3 (Table). Table: 158P
| Factor | OR (95% CI) |
| cN+ vs. cN- | 0.2 (0.1-0.5) |
| HER2+ vs. LumB HER2+ lum vs. LumB Triple neg. vs. LumB | 75.2 (6.9-821) 7.9 (2.4-25.7) 1.5 (0.5-4.2) |
| TIL medium vs. low TIL high vs. low | 2.3 (0.8-6.9) 5.1 (1.4-19) |
| Grade III vs. II | 4.9 (1.2-20) |
| PD1/FOXP3 high vs. low | 4.7 (1.0-23) |
Conclusions
High TIL density and proinflammatory microenviroment are independently associated with total pCR, along with molecular HER2 subtypes, high grade and clinically negative nodes.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Institute of Oncology Ljubljana.
Funding
Slovenian Research Agency.
Disclosure
All authors have declared no conflicts of interest.