The tumor-infiltrating lymphocytes (TILs), especially stromal TILs, have showed a prognostic role in human epidermal growth factor receptor 2 (HER2)-positive and triple negative breast cancer. Stromal TILs are associated with higher pathological complete remission (pCR) rates after neoadjuvant chemotherapy. However, the relation between stromal TILs in primary breast cancer and axillary nodal metastasis remains uncertain.
A retrospective review of pathological reports of 763 patients with breast infiltrating ductal carcinoma (IDC) was conducted. The gene expression and clinical data of 662 IDC cases were downloaded from the TCGA database. In silico analysis was based on the gene expression data. The “Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data” (ESTIMATE) algorithm was used to calculate the stromal and immune scores in N0 and N+ cases.
In HER2+ breast cancer, the fractions of stromal TILs are higher than 30% (37.57% versus 19.67%, P=0.01) and 40% (25.97% vs 8.20%, P=0.003) in lymph node negative cases comparing to nodal metastasis cases. The fractions of stromal TILs in HER2- breast cancer showed no difference between N0 and N+ stage cases. We further compare the fractions of stromal TILs between N0 and N+ cases in different subtypes of breast cancer cases. The stromal TILs (%) is only higher in primary tumors of N0 HER2 amplified breast cancer cases than N+ cases (P=0.014). The stromal TILs (%) of primary tumors are similar between N0 and N+ cases in Luminal A (hormone receptor (HR)+/HER2-) (P=0.261), Luminal B (HR+/HER2+) (P=0.838) and triple negative (HR-/HER2-) subtypes (P=0.456). The primary tumors immune scores of N0 and N+ cases show no significantly difference in HER2+/- breast cancer. The stromal scores of N+ cases are higher than N0 cases in HER2+ breast cancer (P=0.015). The stromal scores are similar between N0 and N+ cases in HER2- breast cancer.
Stromal TILs(%) N0(cases) % N+(cases) % P value Her2+ 0-9 72 39.78 28 45.90 10- 109 60.22 33 54.10 0.401 0-19 101 55.80 40 65.57 20- 80 44.75 21 34.43 0.181 0-29 113 62.43 49 80.33 30- 68 37.57 12 19.67 0.01 0-39 134 74.03 56 91.8 40- 47 25.97 5 8.2 0.003 Stromal TILs(%) N0(cases) % N+(cases) % P value Her2+ 0-9 219 59.03 83 55.70 10- 152 40.97 66 44.30 0.487 0-19 286 77.09 115 77.18 20- 85 22.91 34 22.82 0.982 0-29 313 84.37 124 83.22 30- 58 15.63 25 16.78 0.747 0-39 335 90.30 135 90.60 40- 36 9.70 14 9.4 0.914
The higher fraction of stromal TILs is negatively related to lymph nodes metastasis in her2-positive breast cancer. Since the stromal fraction of tumor tissue may be higher in HER2+ N+ breast cancer, it also tends to be associated with nodal metastasis. In total, it is not the absolute quantity of immune cells, but the relative quantity of TILs in tumor stroma (which we evaluated as stromal TILs (%)) makes a vital role in predicting nodal stage of HER2 amplified IDC.
Weiqichun.
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All authors have declared no conflicts of interest.