Table 1.

Summary of previous studies on the prognostic value of TILs in ER+ breast cancer.

Study	Patient population	Treatment	Method of lymphocyte assessment	Impact of sTILs in prognosis	Impact of iTILs on prognosis
Loi et al.78	BIG 02-98 trial (n = 1078)	Adjuvant anthracycline chemotherapy ± taxane	Full face H&E sections—TILs assessed as a continuous variable	Each 10% increment in sTILs associated with worse OS (HR: 1.1, p = 0.04044) on univariate analysis	No association with DFS or OS.
Ali et al.86	Mixed RCT samples and clinical cohorts (n = 5961)	Variable (adjuvant)	IHC for CD8+ cells on tissue microarrays (TILs assessed as a categorical variable, present vs. not present)	No association with BCSS.	The presence of any iTILs is associated with worse BCSS (HR: 1.16; 95% CI: 1.02–1.32]).
					Association lost on multivariate analysis.
Dieci et al.87	Two RCT cohorts (n = 463)	Adjuvant chemotherapy vs. no chemotherapy	Full face H&E sections. TILs assessed as both continuous and categorical variables.	No association with DFS or OS.	No association with DFS or OS.
Denkert al.9	Meta-analysis of 6 neoadjuvant trials (n = 832)	Various neoadjuvant chemotherapy regimens	Core biopsies. TILs were classified as low (0–10%), intermediate (11–59%), or high (60–100%).	Intermediate TILs were associated with worse DFS (HR: 1.50, 95% CI: 1.09–2.06) and OS (HR: 2.45, 95% CI: 1.61–3.70) vs. low TILs.	N/A
				High TILs associated with worse OS (HR: 1.79, 95% CI: 1.02–3.15) vs. low TILs. No association with DFS.
Sobral-Leite et al.88	Retrospective analysis of a multicenter trial (n = 563)	Tamoxifen or no adjuvant therapy	IHC for CD4, CD8, and FOXP3 cells	CD4 and FOXP3 lymphocytes were not significantly associated with prognosis. Patients with high CD8 cells had an increased risk of recurrence (HR = 1.98; 95% CI: 1.14–3.41)	N/A

BCSS breast cancer-specific survival, DFS disease-free survival, IHC immunohistochemistry, iTILs intratumoural TILs, OS overall survival, RCT randomized controlled trial, sTILs stromal TILs.