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Immune characterization of breast cancer metastases: prognostic implications.

ABSTRACT: Tumor-infiltrating lymphocytes (TILs) evaluated in primary breast cancer (BC) convey prognostic information. Limited data in the metastatic setting are available.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.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).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.

SUBMITTER: Dieci MV

PROVIDER: S-EPMC6013851 | biostudies-other | 2018 Jun

REPOSITORIES: biostudies-other

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Immune characterization of breast cancer metastases: prognostic implications.

Dieci Maria Vittoria MV Tsvetkova Vassilena V Orvieto Enrico E Piacentini Federico F Ficarra Guido G Griguolo Gaia G Miglietta Federica F Giarratano Tommaso T Omarini Claudia C Bonaguro Serena S Cappellesso Rocco R Aliberti Camillo C Vernaci Grazia G Giorgi Carlo Alberto CA Faggioni Giovanni G Tasca Giulia G Conte Pierfranco P Guarneri Valentina V

Breast cancer research : BCR 20180622 1

<h4>Background</h4>Tumor-infiltrating lymphocytes (TILs) evaluated in primary breast cancer (BC) convey prognostic information. Limited data in the metastatic setting are available.<h4>Methods</h4>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.<h4>Results</h4>TILs levels on metastasis were generally low (median 5%) and did not differ between TN and HER2+ tumors. Younger p ...[more]

PMID: 29929548

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Project description:BackgroundLiver metastasis is a significant adverse predictor of overall survival (OS) among breast cancer patients. The purpose of this study was to determine the risk and prognostic factors of breast cancer with liver metastases (BCLM).MethodsData on 311,573 breast cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database and 1728 BCLM patients from Fudan University Shanghai Cancer Center (FUSCC) were included. Logistic regression was used to identify risk factors for liver metastasis. Cox proportional hazards regression model was adopted to determine independent prognostic factors in BCLM patients.ResultsYoung age, invasive ductal carcinoma, higher pathological grade, and subtype of triple-negative and human epidermal growth factor receptor 2 positive (HER2+) were risk factors for developing liver metastasis. The median OS after liver metastasis was 20.0 months in the SEER database and 27.3 months in the FUSCC dataset. Molecular subtypes also played a critical role in the survival of BCLM patients. We observed that hormone receptor-positive (HR+)/HER2+ patients had the longest median OS (38.0 for SEER vs. 34.0 months for FUSCC), whereas triple-negative breast cancer had the shortest OS (9.0 vs. 15.6 months) in both SEER and FUSCC. According to the results from the FUSCC, the subtype of HR+/HER2+ (hazard ratio (HR) = 2.62; 95% confidence interval (CI) = 1.88-3.66; P < 0.001) and HR-/HER2+ (HR = 3.43; 95% CI = 2.28-5.15; P < 0.001) were associated with a significantly increased death risk in comparison with HR+/HER2- patients if these patients did not receive HER2-targeted therapy. For those who underwent HER2-targeted therapy, however, HR+/HER2+ subtype reduced death risk compared with HR+/HER2- subtype (HR = 0.74; 95% CI = 0.58-0.95; P < 0.001).ConclusionsBreast cancer patients at a high risk for developing liver metastasis deserve more attention during the follow-up. BCLM patients with HR+/HER2+ subtype displayed the longest median survival than HR+/HER2- and triple-negative patients due to the introduction of HER2-targeted therapy and therefore it should be recommended for HER2+ BCLM patients.

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Immune characterization of breast cancer metastases: prognostic implications.

Publications

Immune characterization of breast cancer metastases: prognostic implications.

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