Abstract PS5-08: Comparison of PD-L1 protein expression between primary tumors and metastatic lesions in triple negative breast cancers
Authors: Rozenblit Mariya , Huang Richard , Danziger Natalie , Alexander Brian , Ramkissoon Shakti , Blenman Kim , Ross Jeffrey , Rimm David , Pusztai Lajos 
Published: February 2021

Background: Several recent studies that compared small cohorts of metastatic and primary lesions, suggested substantial heterogeneity in tumor infiltrating lymphocyte count, immune gene expression and PD-L1 protein expression across different metastatic sites and between primary breast cancers and metastasis. Understanding the frequency of PD-L1 positivity rates across different tissue sites can indicate differences in the immune microenvironment and may also guide biopsy site selection. We compared PD-L1 positivity on immune cells and tumor cells in primary and metastatic triple negative breast cancer tumors (TNBC).Methods: A retrospective data analysis of the Foundation Medicine PD-L1 IHC database was conducted on 340 cases of TNBC. PD-L1 positivity was determined by IHC using SP142CDx. Results are reported as percent of PD-L1 stained immune cells (IC) in the tumor area. A tumor was considered PD-L1 positive if ≥ 1% IC stained positive with PD-L1. As an exploratory analysis, PD-L1 positivity of tumor cells (TC) was also assessed. PD-L1 percent positive staining results are reported as means with 95% CI. The proportion of PD-L1 positive and negative IC and TC in primary tumors vs metastatic sites was compared using Chi-Square test. Prism 8 was used for all data analysis.Results: All patients were female, with median age 56 years (range 26-89); 179 samples were from primary tumors and 161 from metastatic lesions, representing 15 different tissue sites. Overall, PD-L1 expression on immune cells was statistically significantly more frequent in primary tumors compared to metastatic sites (63.7% [n=114] vs 42.9% [n=69]), p&lt;0.0001). This was driven by the lower PD-L1 positivity rates in skin (23.8%, 95% CI: 8.22% - 47.2%), liver (17.4%, 95%CI: 5.00% - 38.8%) and bone (16.7%, 95%CI: 2.10% - 48.4%) metastases. Lung (68.8%, 95% CI: 41.3 - 90.0), soft tissues (65.2%, 95% CI: 42.7 - 83.6) and lymph nodes 51.1%, 95% CI (35.8 - 66.3) had PD-L1 % positivity rates similar to primary tumors. PD-L1 expression was rare on tumor cells in both the breast and metastatic sites (8.3% vs 4.3%, p=0.13). Conclusion: We observed substantial heterogeneity in PD-L1 positivity rates across metastatic sites. Lung, soft tissues and lymph node metastases had PD-L1 % positivity rates that were similar to that of primary tumors whereas skin, liver and bone metastases had significantly lower PD-L1 % positivity rates. These results raise the possibility that response to immune therapy could depend on the location and the PD-L1 positivity of the metastatic site. Limited current experience in breast cancer is not sufficient to correlate tumor response with PD-L1 expression in metastases, but as more patients receive treatment, this could be examined in the future.

Table 1: Sample Characteristics and % PD-L1 positivity on immune cellsSample typeTotal N (%)N PD-L1 positive (%, 95% CI)Primary Tumor179 (52.6)114 (63.7%, 56.2% - 70.7%)Metastatic Lesion161 (47.4)69 (42.9%, 35.1% - 50.9%)Sites of MetastasesN (% of metastatic samples)N PD-L1 positive (%, 95% CI)Lung16 (10.0)11 (68.8%, 41.3% - 90.0%)Soft Tissues23 (14.3)15 (65.2%, 42.7% - 83.6%)Lymph Nodes45 (28.0)23 (51.1%, 35.8% - 66.3%)Skin21 (13.0)5 (23.8%, 8.22% - 47.2%)Liver23 (14.3)4 (17.4%, 5.00% - 38.8%)Bone12 (7.5)2 (16.7%, 2.10% - 48.4%)Brain9 (5.6)5Mediastinum4 (2.5)1Pleura2 (1.2)0Muscle1 (&lt;1)0Omentum1 (&lt;1)1Ovary1 (&lt;1)0Pelvis1 (&lt;1)0Retroperitoneum1 (&lt;1)0Adrenal Gland1 (&lt;1)1

Table 2: Comparison of PD-L1 positivity in primary versus metastatic sitesTissuePDL1+ Immune CellPDL1- Immune CellP valuePDL1+ Tumor CellPDL- Tumor CellP valuePrimary114650.0001151640.1313Metastasis69927154

Citation Format: Mariya Rozenblit, Richard Huang, Natalie Danziger, Brian Alexander, Shakti Ramkissoon, Kim Blenman, Jeffrey Ross, David Rimm, Lajos Pusztai. Comparison of PD-L1 protein expression between primary tumors and metastatic lesions in triple negative breast cancers [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS5-08.