Abstract:
Background: Tumors commonly are infiltrated by leukocytes, or tumor infiltrating leukocytes (TILs). It remains unclear,
however, if the density and type of individual TILs has a direct or simply correlative role in promoting poor prognosis in
breast cancer patients. Breast cancer in Kenyan women is aggressive with presentation at a young age, with advanced
grade (grade III), large tumor size (>2.0 cm), and poor prognosis. We previously observed that the tumors were
predominantly estrogen receptor positive (ER+) but also included both a high percentage of triple negative tumors and
also increased immune cell infiltration within the tumors. We used breast tumor tissues from each patient to make tissue
microarrays that were then stained for leukocyte and myeloid markers including CD4, CD8, CD20, CD25, CD68, and
CD163 using immunohistochemical techniques. The immune cell infiltration into the cancer tissue included increased
numbers of macrophages (CD68+), helper T cells (CD4+), and CD25+ lymphocytes compared to benign tissue.
Results: This study characterized the grade, molecular subtypes, and proliferation index of these tumors and determined
if TIL density was enriched across any of these factors. We analyzed 49 malignant patient tissue samples for this study.
The patient population had a mean age of 51.9 years. The tumors analyzed were heterogeneous by grade: grade I (6%),
grade II (47%), and grade III (39%). Most patients presented with large tumors (>2.0 cm) (69%). We classified the tumors
into molecular subtypes based on clinical marker expression. Based on this analysis, the molecular subtype distribution
was heterogeneous with luminal B (41%), basal/triple negative (TN) (37%), luminal A (14%) and HER2 (8%) breast cancer
subtypes. While the basal/TN subtype had a much higher proliferative index (Ki-67+) than did the other molecular
subtypes, we did not see a significant correlation between TIL density and either subtype or tumor grade. Therefore,
TIL density is independent of molecular subtype and grade.
Conclusion: This study identified a Kenyan patient cohort that develops large, high-grade tumors primarily of the luminal
B and basal molecular subtypes. After analyzing the TILs within these tumors, we found that immune cell infiltration of
these tumors correlated with increased proliferation but not grade or molecular subtype. Future research is required
to determine if the aberrant recruitment of TILs to tumors contributes to cancer progression and response to cancer
treatments.
