Immune characterization of breast cancer metastases: Prognostic implications

Maria Vittoria Dieci, Vassilena Tsvetkova, Enrico Orvieto, Federico Piacentini, Guido Ficarra, Gaia Griguolo, Federica Miglietta, Tommaso Giarratano, Claudia Omarini, Serena Bonaguro, Rocco Cappellesso, Camillo Aliberti, Grazia Vernaci, Carlo Alberto Giorgi, Giovanni Faggioni, Giulia Tasca, Pierfranco Conte, Valentina Guarneri

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article number62
JournalBreast Cancer Research
Volume20
Issue number1
DOIs
Publication statusPublished - Jun 22 2018

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Tumor-Infiltrating Lymphocytes
Breast Neoplasms
Neoplasm Metastasis
Survival
Neoplasms

Keywords

  • HER2
  • Metastatic breast cancer
  • PD-L1
  • Triple negative
  • Tumor-infiltrating lymphocytes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Immune characterization of breast cancer metastases : Prognostic implications. / Dieci, Maria Vittoria; Tsvetkova, Vassilena; Orvieto, Enrico; Piacentini, Federico; Ficarra, Guido; Griguolo, Gaia; Miglietta, Federica; Giarratano, Tommaso; Omarini, Claudia; Bonaguro, Serena; Cappellesso, Rocco; Aliberti, Camillo; Vernaci, Grazia; Giorgi, Carlo Alberto; Faggioni, Giovanni; Tasca, Giulia; Conte, Pierfranco; Guarneri, Valentina.

In: Breast Cancer Research, Vol. 20, No. 1, 62, 22.06.2018.

Research output: Contribution to journalArticle

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 2018, 'Immune characterization of breast cancer metastases: Prognostic implications', Breast Cancer Research, vol. 20, no. 1, 62. https://doi.org/10.1186/s13058-018-1003-1
Dieci, Maria Vittoria ; Tsvetkova, Vassilena ; Orvieto, Enrico ; Piacentini, Federico ; Ficarra, Guido ; Griguolo, Gaia ; Miglietta, Federica ; Giarratano, Tommaso ; Omarini, Claudia ; Bonaguro, Serena ; Cappellesso, Rocco ; Aliberti, Camillo ; Vernaci, Grazia ; Giorgi, Carlo Alberto ; Faggioni, Giovanni ; Tasca, Giulia ; Conte, Pierfranco ; Guarneri, Valentina. / Immune characterization of breast cancer metastases : Prognostic implications. In: Breast Cancer Research. 2018 ; Vol. 20, No. 1.
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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.",
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T1 - Immune characterization of breast cancer metastases

T2 - Prognostic implications

AU - Dieci, Maria Vittoria

AU - Tsvetkova, Vassilena

AU - Orvieto, Enrico

AU - Piacentini, Federico

AU - Ficarra, Guido

AU - Griguolo, Gaia

AU - Miglietta, Federica

AU - Giarratano, Tommaso

AU - Omarini, Claudia

AU - Bonaguro, Serena

AU - Cappellesso, Rocco

AU - Aliberti, Camillo

AU - Vernaci, Grazia

AU - Giorgi, Carlo Alberto

AU - Faggioni, Giovanni

AU - Tasca, Giulia

AU - Conte, Pierfranco

AU - Guarneri, Valentina

PY - 2018/6/22

Y1 - 2018/6/22

N2 - 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.

AB - 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.

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KW - Metastatic breast cancer

KW - PD-L1

KW - Triple negative

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