BACKGROUND: Tumor-infiltrating lymphocytes (TILs) evaluated in primary breast cancer (BC) convey prognostic information. Limited data in the metastatic setting are available. METHODS: Secondary lesions from 94 BC patients, 43 triple-negative (TN) and 51 HER2-positive, were evaluated for TILs and expression of CD8, FOXP3, and PD-L1 by immunohistochemistry. RESULTS: TILs levels on metastasis were generally low (median 5%) and did not differ between TN and HER2+ tumors. Younger patients showed significantly lower TILs (p = 0.002). In HER2+ patients, TILs were higher in lung metastases as compared to other sites (p = 0.038). TILs composition was different across metastatic sites: skin metastases presented higher FOXP3 (p = 0.002) and lower CD8/FOXP3 ratio (p = 0.032). Patients treated for metastatic BC prior to biopsy had lower CD8 (overall: p = 0.005, HER2+: p = 0.011, TN: p = 0.075). In TN patients, median overall survival (OS) was 11.8 and 62.9 months for patients with low and high TILs, respectively (HR 0.29, 95%CI 0.11-0.76, log-rank p = 0.008). CD8/FOXP3 ratio was also prognostic in TN patients (median OS 8.0, 13.2, and 54.0 months in 1st, 2nd and 3th tertile, log-rank p = 0.019). Both TILs and CD8/FOXP3 ratio were independent factors at multivariate analysis. Counterintuitively, in HER2+ BC, low TILs tumors showed better prognosis (median OS 53.7 vs 39.9 months in TILs low and TILs high, not statistically significant). CONCLUSIONS: Our findings indicate the relevance of TILs as prognostic biomarker for TNBC even in the advanced setting and provide novel hypothesis-generating data on potential sources of immune heterogeneity of metastatic BC.

Immune characterization of breast cancer metastases: prognostic implications / Dieci, Mv; Tsvetkova, V; Orvieto, E; Piacentini, F; Ficarra, G; Griguolo, G; Miglietta, F; Giarratano, T; Omarini, C; Bonaguro, S; Cappellesso, R; Aliberti, C; Vernaci, G; Giorgi, Ca; Faggioni, G; Tasca, G; Conte, P; Guarneri, V.. - In: BREAST CANCER RESEARCH. - ISSN 1465-542X. - 20:62(2018), pp. 1-1. [10.1186/s13058-018-1003-1]

Immune characterization of breast cancer metastases: prognostic implications.

Dieci MV;Piacentini F;Omarini C;Conte P;Guarneri V.
2018

Abstract

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) evaluated in primary breast cancer (BC) convey prognostic information. Limited data in the metastatic setting are available. METHODS: Secondary lesions from 94 BC patients, 43 triple-negative (TN) and 51 HER2-positive, were evaluated for TILs and expression of CD8, FOXP3, and PD-L1 by immunohistochemistry. RESULTS: TILs levels on metastasis were generally low (median 5%) and did not differ between TN and HER2+ tumors. Younger patients showed significantly lower TILs (p = 0.002). In HER2+ patients, TILs were higher in lung metastases as compared to other sites (p = 0.038). TILs composition was different across metastatic sites: skin metastases presented higher FOXP3 (p = 0.002) and lower CD8/FOXP3 ratio (p = 0.032). Patients treated for metastatic BC prior to biopsy had lower CD8 (overall: p = 0.005, HER2+: p = 0.011, TN: p = 0.075). In TN patients, median overall survival (OS) was 11.8 and 62.9 months for patients with low and high TILs, respectively (HR 0.29, 95%CI 0.11-0.76, log-rank p = 0.008). CD8/FOXP3 ratio was also prognostic in TN patients (median OS 8.0, 13.2, and 54.0 months in 1st, 2nd and 3th tertile, log-rank p = 0.019). Both TILs and CD8/FOXP3 ratio were independent factors at multivariate analysis. Counterintuitively, in HER2+ BC, low TILs tumors showed better prognosis (median OS 53.7 vs 39.9 months in TILs low and TILs high, not statistically significant). CONCLUSIONS: Our findings indicate the relevance of TILs as prognostic biomarker for TNBC even in the advanced setting and provide novel hypothesis-generating data on potential sources of immune heterogeneity of metastatic BC.
2018
22-giu-2018
20
62
1
1
Immune characterization of breast cancer metastases: prognostic implications / Dieci, Mv; Tsvetkova, V; Orvieto, E; Piacentini, F; Ficarra, G; Griguolo, G; Miglietta, F; Giarratano, T; Omarini, C; Bonaguro, S; Cappellesso, R; Aliberti, C; Vernaci, G; Giorgi, Ca; Faggioni, G; Tasca, G; Conte, P; Guarneri, V.. - In: BREAST CANCER RESEARCH. - ISSN 1465-542X. - 20:62(2018), pp. 1-1. [10.1186/s13058-018-1003-1]
Dieci, Mv; Tsvetkova, V; Orvieto, E; Piacentini, F; Ficarra, G; Griguolo, G; Miglietta, F; Giarratano, T; Omarini, C; Bonaguro, S; Cappellesso, R; Aliberti, C; Vernaci, G; Giorgi, Ca; Faggioni, G; Tasca, G; Conte, P; Guarneri, V.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1163807
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