Tumour-infiltrating lymphocytes in non-invasive breast cancer: A systematic review and meta-analysis
Rafael Caparica,
Marco Bruzzone,
Elisa Agostinetto,
Maria Alice Franzoi,
Marcello Ceppi,
Nina Radosevic-Robin,
Frédérique Penault-Llorca,
Karen Willard-Gallo,
Sherene Loi,
Roberto Salgado,
Evandro de Azambuja
Affiliations
Rafael Caparica
Institut Jules Bordet, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium
Marco Bruzzone
Clinical Epidemiology Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy
Elisa Agostinetto
Institut Jules Bordet, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium; Humanitas Clinical and Research Center – IRCCS, Humanitas Cancer Center, via Manzoni 56, 20089, Rozzano, Milan, Italy; Humanitas University, Department of Biomedical Sciences, via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Milan, Italy; Corresponding author. Institut Jules Bordet, Boulevard de Waterloo 121, 1000, Brussels, Belgium.
Maria Alice Franzoi
Institut Jules Bordet, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium
Marcello Ceppi
Clinical Epidemiology Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy
Nina Radosevic-Robin
INSERM U1240, University Clermont Auvergne, Centre Jean Perrin, Department of Pathology, Clermont-Ferrand, France
Frédérique Penault-Llorca
INSERM U1240, University Clermont Auvergne, Centre Jean Perrin, Department of Pathology, Clermont-Ferrand, France
Background: The role of tumour infiltrating lymphocytes (TILs) as a biomarker in non-invasive breast cancer is unclear. This meta-analysis assessed the prognostic impact of TIL levels in patients with non-invasive breast cancer. Methods: Systematic literature search was performed to identify studies assessing local recurrence in patients with non-invasive breast cancer according to TIL levels (high vs. low). Subgroup analyses per local recurrence (invasive and non-invasive) were performed. Secondary objectives were the association between TIL levels and non-invasive breast cancer subtypes, age, grade and necrosis. Odds ratios (ORs) and 95% confidence intervals (CI) were extracted from each study and a pooled analysis was conducted with random-effect model. Results: Seven studies (N = 3437) were included in the present meta-analysis. High-TILs were associated with a higher likelihood of local recurrence (invasive or non-invasive, N = 2941; OR 2.05; 95%CI, 1.03–4.08; p = 0.042), although with a lower likelihood of invasive local recurrence (N = 1722; OR 0.69; 95%CI, 0.49–0.99; p = 0.042). High-TIL levels were associated with triple-negative (OR 3.84; 95%CI, 2.23–6.61; p < 0.001) and HER2-positive (OR 6.27; 95%CI, 4.93–7.97; p < 0.001) subtypes, high grade (OR 5.15; 95%CI, 3.69–7.19; p < 0.001) and necrosis (OR 3.09; 95%CI, 2.33–4.10; p < 0.001). Conclusions: High-TIL levels were associated with more aggressive tumours, a higher likelihood of local recurrence (invasive or non-invasive) but a lower likelihood of invasive local recurrence in patients with non-invasive breast cancer.
