Abstract P4-08-04: PD-L1 expression and prognosis in triple negative breast cancer (TNBC): An analysis of 265 patients (pts) treated with standard therapy for stage I-III disease
Authors: Dieci MV , Orvieto E , Tsvetkova V , Griguolo G , Miglietta F , Bonaguro S , Tasca G , Giorgi CA , Cumerlato E , Guarneri V , Conte P 
Published: May 2019

Abstract
Background: Targeting the PD-L1/PD-1 axis has proved to be effective in various cancers, including promising data for metastatic TNBC pts. The evaluation of PD-L1 expression is limited by the lack of standardized methods. Here we sought to evaluate the prognostic role of PD-L1 expression in a large cohort of patients with non-metastatic TNBC treated with standard therapy.
Methods:
Consecutive patients diagnosed with stage I-III TNBC (ER and PgR &lt;10%, HER2 0/1+ or ISH non amplified) between May 2012 and December 2015 and treated at the Istituto Oncologico Veneto of Padova were included. All patients received treatment with surgery, chemotherapy (neoadjuvant or adjuvant) and radiotherapy (when indicated).
For each case, one FFPE tumor slide was stained for PD-L1 with the PD-L1 IHC 73-10 Research Use Only assay developed by Agilent Technologies and one slide was stained for cytokeratins with MNF116 (to distinguish MNF116+ tumor cells from MNF116- stromal cells). Digital slides were evaluated by a specifically-developed Visiopharm® software application. Following alignment of the PD-L1 and MNF116 digital slides, the software analyzed PD-L1 expression on tumor cells (% of positively stained tumor cells/total tumor cells) and stromal cells (% of positively stained stromal cells/total stromal cells). Disease-free survival (DFS) was calculated from diagnosis to relapse or death. In survival analyses, PD-L1 was evaluated as continuous and categorical variable.
Results:
265 TNBC pts were evaluated. Median PD-L1 was 2.6% (Q1-Q3 0%-18.6%) on tumor cells and 5.2% (Q1-Q3 0.2%-25.4%) on stromal cells. PD-L1 levels on tumor and stromal cells were positively correlated (spearman's 0.938, p&lt;0.001). For further analyses, PD-L1 on stromal cells was considered. Higher PD-L1 was associated with age &lt;50 yrs (p=0.011), Grade 3 (p=0.003) and Ki67 &gt;30% (p=0.005). Lower PD-L1 was observed in lobular and apocrine tumors (p=0.001).Cox model for DFS showed HR=0.99 (95%CI 0.97-1.00, p=0.059) for every 1% PD-L1 increment.
3-yrs DFS was 86% for pts with PD-L1&gt;20% (n=88, 29%) vs 75% for pts with PD-L1&lt;20% (n=177, 71%): HR 0.52, 95%CI 0.28-0.97, p=0.039. PD-L1 at 20% cut-off maintained prognostic value in multivariate model including stage (HR 0.48, 95%CI 0.25-0.89, p=0.021).
Of the 265 pts included, 108 received neoadjuvant chemotherapy (NACT). Of the 78 pts with residual disease after NACT, 61 had pre- and post-NACT samples evaluable for PD-L1. PD-L1 increased from pre- to post-NACT: median 2.7% (Q1-Q3 0%-26.9%) vs 20.1% (Q1-Q3 5.9%-41.4%), p&lt;0.001. Pts with PD-L1&gt;20% post-NACT showed improved DFS: 3-yrs DFS 68% vs 43% (HR 0.44, 95%CI 0.20-0.96, p=0.039), whereas PD-L1 pre-NACT did not show significant association with DFS in this subgroup (HR 0.47, 95%CI 0.23-1.40, p=0.218).
Conclusions:
PD-L1 expression evaluated with a software-assisted method was prognostic for stage I-III TNBC pts treated with standard therapy. The significant increase of PD-L1 on residual disease post-NACT supports the rationale to evaluate the efficacy of anti-PD-L1 drugs in this high-risk population.
Citation Format: Dieci MV, Orvieto E, Tsvetkova V, Griguolo G, Miglietta F, Bonaguro S, Tasca G, Giorgi CA, Cumerlato E, Guarneri V, Conte P. PD-L1 expression and prognosis in triple negative breast cancer (TNBC): An analysis of 265 patients (pts) treated with standard therapy for stage I-III disease [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-08-04.