Differential Effects of Anthracycline-based Neoadjuvant Chemotherapy on Stromal and Intratumoral FOXP3⁺ Tumor-Infiltrating Lymphocytes in Invasive Breast Cancer of No Special Type

BACKGROUND: Neoadjuvant chemotherapy (NAC) plays a crucial role in the management of invasive breast cancer with no special type (IBC-NST), with the immune system's response to cancer heavily relying on the dynamics between tumor-infiltrating lymphocytes (TILs) and cancer cells. In this study, the differential effects of anthracycline-based NAC on stromal and intratumoral foxhead box P3 (FOXP3⁺) TILs expressions were specifically examined. METHODS: In this cross-sectional study, 32 IBC-NST samples were evaluated for pre- and post-NAC FOXP3⁺ TIL expression as well as the changes of FOXP3⁺ TIL expression. Comprehensive data collection regarding subjects' age, tumor size, grade, lymphovascular invasion, regional lymph node metastasis, and receptor status were conducted. Immunohistochemistry was utilized to quantify FOXP3⁺ TILs. The stromal, intratumoral and total FOXP3⁺ TILs expression were then analyzed. RESULTS: Significant reductions in FOXP3⁺ TIL expression post-NAC were observed, with stromal FOXP3⁺ TILs showing a median decrease of 3.6 units in subjetcs aged >50 years (p=0.013) and a median decrease of 13.2 units in subjects with tumors >5 cm after NAC (p=0.006). In contrast, intratumoral FOXP3⁺ TILs remained relatively stable, with minor changes. The total FOXP3⁺ TIL expression, combining stromal and intratumoral components, was significantly decreased with a median of 13.0 units decreased to 5.3 units (p<0.001). CONCLUSION: This study highlights the significant reduction in stromal FOXP3⁺ TIL expression after NAC treatment in IBC-NST subjects, in contrast to the relatively stable intratumoral FOXP3⁺ TILs. Understanding these differences may guide future therapeutic strategies and improve treatment outcomes for IBC-NST.