Higher densities of tumour‐infiltrating lymphocytes and CD4⁺ T cells predict recurrence and progression of ductal carcinoma <i>in situ</i> of the breast

Abstract

Aims Host immunity influences cancer progression and therapeutic response. We investigated the potential of tumour‐infiltrating lymphocytes ( TIL s) around ductal carcinoma in situ ( DCIS ) in predicting recurrence and progression. Methods and results CD 4, CD 8, programmed cell death 1 ( PD ‐1) and programmed cell death ligand 1 (PD‐L1) expression in DCIS from 198 patients was determined by immunohistochemistry. We correlated disease‐free survival ( DFS ), clinicopathological parameters and biomarker expression with TIL density and CD 4/ CD 8 ratio. High TIL density was associated with high nuclear grade ( P &lt; 0.001), DCIS PD‐L1 expression ( P = 0.008), TIL PD‐L1 expression ( P &lt; 0.001), oestrogen ( ER ) negativity ( P &lt; 0.001), progesterone ( PR ) negativity ( P &lt; 0.001), human epidermal growth factor receptor 2 ( HER 2) positivity ( P = 0.002) and triple negativity ( P = 0.001). TIL PD‐L1 expression was associated with triple‐negative DCIS ( P = 0.028). TIL density was associated with molecular subtypes ( P &lt; 0.001). High CD4 + T cell density was associated with high nuclear grade ( P = 0.001), microinvasion ( P = 0.037), ER negativity ( P &lt; 0.001), PR negativity ( P = 0.001), HER 2 positivity ( P = 0.004), triple negativity ( P = 0.023) and PD‐L1 expression in TIL s ( P &lt; 0.011). High CD 4/ CD 8 ratio was associated with PD‐L1 expression in DCIS ( P = 0.035) and TIL s ( P &lt; 0.001). DCIS with higher TIL density disclosed worse DFS ( P = 0.012) and was affirmed with multivariate analysis [95% confidence interval ( CI ) = 1.109–2.554, hazard ratio ( HR ) = 1.683, P = 0.014]. Poorer DFS for ipsilateral invasive recurrence was found for DCIS with higher CD 4 + T cell density ( P = 0.006) or CD 4/ CD 8 ratio ( P = 0.02), confirmed by multivariate analysis for the former (95% CI = 1.369–10.196, HR = 3.736, P = 0.01) and latter (95% CI = 1.311–7.935, HR = 3.225, P = 0.011). Conclusion DCIS with higher TIL density was associated with poorer prognostic parameters and predicted recurrence, while both CD 4 + T cell density and CD 4/ CD 8 ratio were associated with both recurrence and ipsilateral invasive recurrence.