Comparisons of tumor-infiltrating lymphocyte levels and the 21-gene recurrence score in ER-positive/HER2-negative breast cancer

Background: Recent studies have shown that tumors with extensive tumor-infiltrating lymphocytes (TILs) have a higher probability of pathologic complete response, even in luminal/human epidermal growth factor 2 (HER2)-negative breast cancer. We compared TIL levels and the 21-gene recurrence score (RS) in estrogen receptor (ER)-positive/HER2-negative breast cancer. Methods: We evaluated the percentage of stromal TILs in 198 ER-positive/HER2-negative patients in whom RS was obtained by examining slides of surgical specimens by standardized methodology proposed by the international TIL Working Group. TIL levels were categorized as high (≥ 60%), intermediate (11-59%), or low (≤ 10%). All tumors were treatment-naïve. Results: Ninety-seven (49.0%), 88 (44.4%), and 13 patients (6.6%) had low, intermediate, and high TIL levels, respectively. There was a significant but weak correlation between continuous RS and continuous TIL levels (Pearson's R=0.201, p=0.004). The mean RS was significantly highest in high TIL tumors (17.8±10.7 in low TIL tumors, 19.4±8.7 in intermediate TIL tumors, and 26.2±8.2 in high TIL tumors; p=0.014). However, when we compared categorized RS and TIL levels, we found that tumors with high TIL levels tended to have higher RS (≥ 26) but it was not significant (p=0.155). Furthermore, multivariate analysis revealed that high RS was not an independent factor associated with high TIL levels. Chemo-endocrine therapy was more frequently performed among patients with high TILs and less frequently among those with low or intermediate TILs (p< 0.001). Conclusions: Despite of a weak correlation between continuous TIL levels and RS, we found that tumors with high TIL levels tended to have a higher RS in ER-positive/HER2-negative breast cancer. Further study is warranted considering the clinical outcomes.