Abstract P6-07-05: PD-L1 expression and decreased tumor-infiltrating lymphocytes are associated with poor prognosis in patients with triple negative breast cancer
Authors: Mori H , Kubo M , Yamaguti R , Nishimura R , Osako T , Arima N , Okumura Y , Okido M , Yamada M , Kai M , Kishimoto J , Oda Y , Nakamura M 
Published: March 2017

Abstract
Background: Tumor microenvironment has been considered to have an active role in determining the aggressiveness of tumor cells. Recently, programmed cell death ligand-1 (PD-L1) expression or tumor-infiltrating lymphocytes (TILs) are known to be an important prognostic factor of breast cancer. However, the correlation of expression of PD-L1 and TILs still remains unclear. Triple-negative breast cancer (TNBC) is a heterogeneous tumor that encompasses many different subclasses. Further identification of these subclasses is necessary in order to predict prognosis and choose appropriate treatments. Our goal was to correlate PD-L1 expression with clinicopathological features including TILs by using a large cohort of TNBCs.
Patients and Methods: This study included 248 patients with primary TNBC who underwent resection without neoadjuvant chemotherapy at our three hospitals between January 2004 and December 2014. The tumor subtypes were routinely determined immunohistochemically by using resected specimens. IHC scoring for PD-L1 expression was defined in reference to that for HER2 expression. PD-L1 positivity was defined as both IHC 2+ and IHC 3+. Cases were defined as high if stromal TILs ≥50% according to recommendations by the International TILs Working Group.
Results: Of the 248 TNBCs, PD-L1 were expressed as positive in 103 (41.5%) tumors, and TILs were highly present in 118 (47.6%) tumors. PD-L1 expression was significantly correlated with higher levels of TILs (P &lt; 0.0001). There was no significant difference when the prognosis of the patients who had PD-L1-positive tumors was compared with that of the patients who had PD-L1-negative tumors (P = 0.56 in recurrence free survival [RFS] and P = 0.13 in overall survival [OS]). Meanwhile, the patients with high-TILs tumors had longer OS, compared to the patients with low-TILs tumors (P = 0.55 in RFS and P = 0.016 in OS). The analysis in the cross effect between PD-L1 expression and TILs using cox proportional hazards model demonstrated that the PD-L1 expression and TILs are not independent factors(P = 0.0018 in RFS and P = 0.015 in OS). The PD-L1-positive group with low-TILs had significantly shorter survival than the PD-L1-positive group with high-TILs (hazard ratio [HR] = 4.7, 95% confidence interval [CI] 1.6–12.7, P = 0.0067 in RFS; HR = 8.4, 95%CI 2.3-30.3, P = 0.0019 in OS).
Conclusions: Our data indicated that PD-L1 expression was related to higher levels of TILs, and PD-L1-positive tumors with low-TILs were associated with poor prognosis in patients with TNBCs. It is proposed that these biomarkers may be of use for predicting their prognosis and essential in the subclassification of TNBCs.
Citation Format: Mori H, Kubo M, Yamaguti R, Nishimura R, Osako T, Arima N, Okumura Y, Okido M, Yamada M, Kai M, Kishimoto J, Oda Y, Nakamura M. PD-L1 expression and decreased tumor-infiltrating lymphocytes are associated with poor prognosis in patients with triple negative breast cancer [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 P6-07-05.