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TILGen: A Program to Investigate Immune Targets in Breast Cancer Patients - First Results on the Influence of
Franziska Würfel1, Ramona Erber2, Hanna Huebner1
1Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander-University Erlangen-Nuremberg (FAU), Erlangen, Germany.
Background:
Despite advancements in the treatment of primary and metastatic breast cancer, many patients lack a durable response to these treatments. Patients with triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2(HER2)-positive breast cancer who do not have a pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) have a very poor prognosis. Tumor-infiltrating lymphocytes (TILs) have been identified as a predictive marker for pCR after NACT in TNBC and HER2-positive breast cancer. These patient populations could also be suitable for novel treatment strategies including neoepitope-based therapies. This work analyses the effect of TILs on the pCR in neoadjuvantly treated patients in the TILGen study and presents the procedures aimed at establishing neoepitope-based therapies in this study.
Methods:
Neoadjuvantly treated HER2-positive and TNBC patients were eligible for the presented analysis concerning the association between TILs and pCR. A total of 146 patients could be identified within the TILGen study. TILs were evaluated as percentage of stromal tumor tissue in core biopsies at primary diagnosis. The phenotype 'lymphocyte-predominant breast cancer' (LPBC) was associated with pCR by logistic regression adjusted for estrogen receptor status, progesterone receptor status, HER2 status, age at diagnosis, and grading.
Results:
LPBC was seen in 24 (16.4%) patients. In this patient group, 66.7% achieved a pCR, while the pCR rate was 32.8% in patients with a low TIL count. The adjusted odds ratio was 6.60 (95% confidence interval 2.02-21.56; p < 0.01).
Conclusion:
TILs are a strong predictor of pCR in TNBC and HER2-positive breast cancer patients. Implications for the use of this information including the effect on prognosis might help to identify patients most likely to benefit from a neoepitope-based therapy approach.
Insights
High tumor-infiltrating lymphocytes (TILs) predict a better pathological complete response (pCR) in patients with triple-negative breast cancer (TNBC) and HER2-positive breast cancer undergoing neoadjuvant chemotherapy (NACT). This finding supports TILs as a biomarker for novel neoepitope-based therapies.
Area of Science:
- Oncology
- Immunology
- Pathology
Background:
- Advanced breast cancer treatments often lack durable responses.
- Triple-negative breast cancer (TNBC) and HER2-positive breast cancer patients without pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) have a poor prognosis.
- Tumor-infiltrating lymphocytes (TILs) are emerging as predictive markers for pCR in TNBC and HER2-positive breast cancer.
Purpose of the Study:
- To analyze the effect of TILs on pCR in neoadjuvantly treated patients within the TILGen study.
- To evaluate TILs as a predictive marker for pCR in TNBC and HER2-positive breast cancer.
- To explore the potential for establishing neoepitope-based therapies based on TIL levels.
Main Methods:
- Analysis of 146 neoadjuvantly treated HER2-positive and TNBC patients from the TILGen study.
- TILs were quantified as a percentage of stromal tumor tissue in core biopsies at primary diagnosis.
- Logistic regression was used to associate the 'lymphocyte-predominant breast cancer' (LPBC) phenotype with pCR, adjusted for clinical factors.
Main Results:
- The lymphocyte-predominant breast cancer (LPBC) phenotype was observed in 16.4% of patients.
- Patients with LPBC achieved a pCR rate of 66.7%, compared to 32.8% in patients with low TIL counts.
- A significant adjusted odds ratio of 6.60 (p < 0.01) indicated TILs as a strong predictor of pCR.
Conclusions:
- TILs are a robust predictor of pCR in TNBC and HER2-positive breast cancer patients.
- TIL levels can inform prognosis and identify patients likely to benefit from neoepitope-based therapies.
- This study supports the clinical utility of TIL assessment in guiding treatment strategies for specific breast cancer subtypes.
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