Negative Relationship between Post-Treatment Stromal Tumor-Infiltrating Lymphocyte (TIL) and Survival in Triple-Negative Breast Cancer Patients Treated with Dose-Dense Dose-Intense NeoAdjuvant Chemotherapy

SIMPLE SUMMARY: Triple-negative breast cancer (TNBC) continues to have a poor prognosis unless a complete pathological response is achieved after neoadjuvant chemotherapy (NAC). The identification of prognostic factors would help to improve care. The evaluation of tumor-infiltrating lymphocyte (TIL) levels is recommended in patients with breast cancer, but little is known about changes in these levels with treatment. We studied a series of 117 TNBCs treated by dose-dense dose-intense (dd-di) NAC, to identify factors associated with pre- and post-NAC stromal TIL levels, and oncological outcomes. Our findings highlight the complexity of TIL level interpretation and the importance of taking NAC regimen into account when interpreting results. We show that patients with persistently high TIL levels after NAC are at higher risk of relapse and death. ABSTRACT: Background: Patients with triple-negative breast cancers (TNBC) have a poor prognosis unless a pathological complete response (pCR) is achieved after neoadjuvant chemotherapy (NAC). Few studies have analyzed changes in TIL levels following dose-dense dose-intense (dd-di) NAC. Patients and methods: From 2009 to 2018, 117 patients with TNBC received dd-di NAC at our institution. We aimed to identify factors associated with pre- and post-NAC TIL levels, and oncological outcomes relapse-free survival (RFS), and overall survival (OS). Results: Median pre-NAC and post-NAC TIL levels were 15% and 3%, respectively. Change in TIL levels with treatment was significantly correlated with metabolic response (SUV) and pCR. High post-NAC TIL levels were associated with a weak metabolic response after two cycles of NAC, with the presence of residual disease and nodal involvement at NAC completion. In multivariate analyses, high post-NAC TIL levels independently predicted poor RFS and poor OS (HR = 1.4 per 10% increment, 95%CI (1.1; 1.9) p = 0.014 and HR = 1.8 per 10% increment 95%CI (1.3–2.3), p < 0.0001, respectively). Conclusion: Our results suggest that TNBC patients with TIL enrichment after NAC are at higher risk of relapse. These patients are potential candidates for adjuvant treatment, such as immunotherapy, in clinical trials.