Immune characterization of breast cancer metastases: prognostic implications
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...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2018-06-01
|
| Series: | Breast Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13058-018-1003-1 |
| _version_ | 1818942772479000576 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Maria Vittoria Dieci |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T07:16:45Z |
| format | Article |
| id | doaj.art-51b715e5259a4aa8aa3035d2ff94fc36 |
| institution | Directory Open Access Journal |
| issn | 1465-542X |
| language | English |
| last_indexed | 2024-12-20T07:16:45Z |
| publishDate | 2018-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj.art-51b715e5259a4aa8aa3035d2ff94fc362022-12-21T19:48:46ZengBMCBreast Cancer Research1465-542X2018-06-0120111010.1186/s13058-018-1003-1Immune characterization of breast cancer metastases: prognostic implicationsMaria Vittoria Dieci0Vassilena Tsvetkova1Enrico Orvieto2Federico Piacentini3Guido Ficarra4Gaia Griguolo5Federica Miglietta6Tommaso Giarratano7Claudia Omarini8Serena Bonaguro9Rocco Cappellesso10Camillo Aliberti11Grazia Vernaci12Carlo Alberto Giorgi13Giovanni Faggioni14Giulia Tasca15Pierfranco Conte16Valentina Guarneri17Department of Surgery, Oncology and Gastroenterology, University of PadovaDepartment of Surgery, Oncology and Gastroenterology, University of PadovaDepartment of Pathology, Azienda Ospedaliera di PadovaDepartment of Medical and Surgical Sciences of Mother, Child and Adult, University of Modena and Reggio EmiliaDivision of Pathology, University Hospital of ModenaDepartment of Surgery, Oncology and Gastroenterology, University of PadovaDepartment of Surgery, Oncology and Gastroenterology, University of PadovaMedical Oncology 2, Istituto Oncologico Veneto IRCCSDepartment of Medical Oncology, University Hospital of ModenaDepartment of Surgery, Oncology and Gastroenterology, University of PadovaSurgical Pathology and Cytopathology Unit, Department of Medicine, University of PadovaRadiology, Istituto Oncologico Veneto IRCCSDepartment of Surgery, Oncology and Gastroenterology, University of PadovaMedical Oncology 2, Istituto Oncologico Veneto IRCCSMedical Oncology 2, Istituto Oncologico Veneto IRCCSDepartment of Surgery, Oncology and Gastroenterology, University of PadovaDepartment of Surgery, Oncology and Gastroenterology, University of PadovaDepartment of Surgery, Oncology and Gastroenterology, University of PadovaAbstract 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.http://link.springer.com/article/10.1186/s13058-018-1003-1Metastatic breast cancerTumor-infiltrating lymphocytesPD-L1Triple negativeHER2 |
| spellingShingle | 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 Immune characterization of breast cancer metastases: prognostic implications Breast Cancer Research Metastatic breast cancer Tumor-infiltrating lymphocytes PD-L1 Triple negative HER2 |
| title | Immune characterization of breast cancer metastases: prognostic implications |
| title_full | Immune characterization of breast cancer metastases: prognostic implications |
| title_fullStr | Immune characterization of breast cancer metastases: prognostic implications |
| title_full_unstemmed | Immune characterization of breast cancer metastases: prognostic implications |
| title_short | Immune characterization of breast cancer metastases: prognostic implications |
| title_sort | immune characterization of breast cancer metastases prognostic implications |
| topic | Metastatic breast cancer Tumor-infiltrating lymphocytes PD-L1 Triple negative HER2 |
| url | http://link.springer.com/article/10.1186/s13058-018-1003-1 |
| work_keys_str_mv | AT mariavittoriadieci immunecharacterizationofbreastcancermetastasesprognosticimplications AT vassilenatsvetkova immunecharacterizationofbreastcancermetastasesprognosticimplications AT enricoorvieto immunecharacterizationofbreastcancermetastasesprognosticimplications AT federicopiacentini immunecharacterizationofbreastcancermetastasesprognosticimplications AT guidoficarra immunecharacterizationofbreastcancermetastasesprognosticimplications AT gaiagriguolo immunecharacterizationofbreastcancermetastasesprognosticimplications AT federicamiglietta immunecharacterizationofbreastcancermetastasesprognosticimplications AT tommasogiarratano immunecharacterizationofbreastcancermetastasesprognosticimplications AT claudiaomarini immunecharacterizationofbreastcancermetastasesprognosticimplications AT serenabonaguro immunecharacterizationofbreastcancermetastasesprognosticimplications AT roccocappellesso immunecharacterizationofbreastcancermetastasesprognosticimplications AT camilloaliberti immunecharacterizationofbreastcancermetastasesprognosticimplications AT graziavernaci immunecharacterizationofbreastcancermetastasesprognosticimplications AT carloalbertogiorgi immunecharacterizationofbreastcancermetastasesprognosticimplications AT giovannifaggioni immunecharacterizationofbreastcancermetastasesprognosticimplications AT giuliatasca immunecharacterizationofbreastcancermetastasesprognosticimplications AT pierfrancoconte immunecharacterizationofbreastcancermetastasesprognosticimplications AT valentinaguarneri immunecharacterizationofbreastcancermetastasesprognosticimplications |