Abstract P2-05-20: Tumor infiltrating lymphocytes in recurrent HER2+ and triple negative breast cancer: Prognostic value according to tumor phenotype
Authors: Dieci MV , Giaratano T , Miglietta F , Griguolo G , Orvieto E , Falci C , Giorgi CA , Mioranza E , Tasca G , Cappellesso R , Ghiotto C , Conte P , Guarneri V 
Published: March 2017

Abstract
Background: Tumor infiltrating lymphocytes (TILs) have emerged as a prognostic and potential predictive factor in early triple negative (TN) and HER2+ breast cancer (BC). The prognostic role of TILs in advanced disease is largely unknown.
Methods: 109 HER2+ and TNBC patients with available tumor tissue from regional/distant BC recurrence (collected between 2001 and 2015) were identified from a prospectively maintained database at the Istituto Oncologico Veneto of Padova (Italy). Ipsilateral in-breast relapse/second primaries and contralateral BC were excluded from the definition of recurrence. StrTILs were assessed according to consensus guidelines (Salgado, 2014) on hematoxylin and eosin stained slides from BC recurrence samples and, when available, matched primaries. Post-progression survival was calculated as the time from first BC recurrence to last follow up or death.
Results: StrTILs were evaluable on recurrent BC for 72 cases (HER2+ n=43, TN n=29), after exclusion of lymphnode metastases. Median time to recurrence from initial BC diagnosis was longer for HER2+ than TN cases: 37 months (95%CI 23-51) and 18 months (95%CI 13-23), respectively. Accordingly, median time to biopsy of recurrence from initial BC diagnosis was 43 months (95%CI 35-51) for HER2+ patients and 20 months (95%CI 9-31) for TN patients. Site of biopsy was visceral metastasis in 54% and soft tissue metastasis in 46% of cases (similar for HER2+ and TN).
Median StrTILs level on recurrence was 5% (Q1 2,5%, Q3 10%), without differences according to TN or HER2+ phenotype (Student's t-test p=0.5).
In the whole cohort, post-progression survival did not differ for patients with high (&gt;10%) vs low (&lt;10%) StrTILs on recurrence (HR 0.83 95% CI 0.38-1.80, p=0.64).
In the TN subgroup, high StrTILs on recurrence were associated to a better post-progression survival (median not reached vs 12.7 months for StrTILs &gt;10% and &lt;10%, respectively, HR 0.03 95%CI 0.00-3.64, log-rank p=0.019). To the opposite, in the HER2+ subgroup, high StrTILs were associated to worse post-progression survival compared to low StrTILs (median 27.7 vs 41.1 months for high vs low StrTILs, HR 2.93 95%CI 1.17-7.31, log-rank p=0.016). Test for interaction between tumor phenotype and StrTILs was p=0.15. Similar results were obtained when including only those patients maintaining a concordant TN or HER2+ phenotype on both primary tumor and recurrence (n=59).
StrTILs were assessed on matched primary tumors for 43 patients. Overall, no significant StrTILs variation between primary tumor and recurrence was observed (mean change -4.5%, Wilcoxon p=0.5). Mean change was -2.5% and -7% in HER2+ and TN cases (Wilcoxon p=0.63 and p=0.15, respectively). For TN patients with StrTILs &lt;10% on recurrence, a significant reduction from the primary tumor was observed (mean StrTILs 16% and 4% on primary and recurrent BC, respectively, Wilcoxon p 0.008).
Conclusions: Levels of StrTILs on recurrent BC seem to have an opposite effect on prognosis of metastatic BC patients according to tumor phenotype. Immunohistochemical characterization of TILs is ongoing, data will be available for the meeting.
Citation Format: Dieci MV, Giaratano T, Miglietta F, Griguolo G, Orvieto E, Falci C, Giorgi CA, Mioranza E, Tasca G, Cappellesso R, Ghiotto C, Conte P, Guarneri V. Tumor infiltrating lymphocytes in recurrent HER2+ and triple negative breast cancer: Prognostic value according to tumor phenotype [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-05-20.