TILGen: A Program to Investigate Immune Targets in Breast Cancer Patients – First Results on the Influence of Tumor-Infiltrating Lymphocytes

Introduction:

Even though most breast cancer subtypes can be treated well, some patients still lack a durable treatment response. Especially, the management of triple negative breast cancer (TNBC) cases is still challenging. Human epidermal growth factor receptor 2 (HER2) positive and TNBC patients are associated with poor prognosis if neoadjuvant chemotherapy (NACT) does not result in a pathological complete response (pCR). In this context, tumor-infiltrating lymphocytes (TILs) are known for their predictive value in regard to pCR. High numbers of TILs might further allow the use of novel immunotherapeutic treatment strategies including neoepitope-based therapies. The main focus of the TILGen study is to enable the implementation of those novel therapeutic approaches. Within the presented work we analyzed the number of TILs in regard to pCR rates of neoadjuvantly treated patients within the TILGen study.

Methods:

A total of 146 neoadjuvantly treated HER2-positive and TNBC patients enrolled in the TILGen study were identified for further analysis. TILs were evaluated as percentage of stromal tumor tissue in primary core biopsies. Analyzed cases were classified as 'lymphocyte-predominant breast cancer' (LPBC, > 50% stromal TILs) or non-LPBC (≤50% stromal TILs) and association with pCR by logistic regression adjusted for estrogen receptor status, progesterone receptor status, HER2 status, age at diagnosis, and grading.

Results:

The phenotype LPBC could be detected in 24 (16.4%) patients, from which 66.7% achieved a pCR. In contrast non-LPBC cases had a pCR rate of only 32.8%. The adjusted odds ratio was 6.60 (95% confidence interval 2.02 – 21.56; p < 0.01).

Conclusion:

In this study we were able to confirm the predictive value of TILs for pCR in HER2-positive and TNBC cases. In addition, TIL quantification might help to identify breast cancer patients who will most likely benefit from a neoepitope-based therapy approach.