Abstract P2-08-03: PD-L1 protein expression in relation to Recurrence Score values in early stage ER+HER2- breast cancer
Authors: Blenman Kim RM , Harigopal Malini , Huang Richard , Reisenbichler Emily , Qing Tao , Ibrahim Eiman , Singh Kamaljeet , Ramkissoon Shakti , Mustimbo Roberts , Ross Jeffrey , Pusztai Lajos 
Published: March 2022

Background: There is interest in exploring neoadjuvant chemotherapy + immune checkpoint inhibitor therapy in stage II-III ER+ breast cancer, but there is no information on correlation between PD-L1 expression and Oncotype DX Recurrence Score (RS) or histologic grade that currently inform patient selection for adjuvant/neoadjuvant chemotherapy. The goal of this study was to assess associations between PD-L1 protein expression, RS, tumor grade, and stromal tumor infiltrating lymphocyte (TIL) score in early stage ER+ cancers. Methods:. Formalin fixed surgical pathology blocks of 213 patients who had RS determination as routine care between 2012 and 2017 were retrieved from Yale Pathology. PD-L1 immunohistochemistry was performed with the SP142 assay by Foundation Medicine, cases with ≥1% tumor infiltrating immune cell positivity in the tumor area were considered PD-L1+. TIL scores were determined prospectively as part of this study by breast pathologists following the international TIL scoring guidelines. We compared PD-L1 expression positivity rates across RS (&lt;11, 11-25, &gt;25) and TIL categories (&lt;10%, 10-29%, &gt;30%), and tumor grade using Wilcoxon and Chi-square tests. Multivariate analysis was performed using logistic regression. Results: Patient characteristics are shown in the table below. PD-L1 results were available for 201, and TIL scores for 203 patients. Overall, 53% of cases were PD-L1+, but expression levels were low, among the positive cases only 14% had positivity ≥ 5%. PD-L1 expression was significantly higher among cases with RS&gt;25 (78% PD-L1+, among these 19% had PD-L1+ ≥5%), compared to RS&lt;11 and RS 11-25 which were similar to each other (overall 48% were PD-L1+, among these 10% had PD-L1 ≥ 5%). PD-L1 positivity also correlated significantly with TIL score, tumor grade and T stage (tumor size). Among cancers with TIL ≥ 30%, 92% were PD-L1+ and 59% of these had PD-L1 ≥5% compared to 42% PD-L1+ (4% with PD-L1 ≥5%) among TIL&lt; 10%. Grade 3 cancers also had higher PD-L1 positivity (82%, among these 22% with PD-L1 &gt; 5%) compared to grade 2 (49% PD-L1+) or 1 tumors (48% PD-L1+, all at 1% level). T2 and T3 tumors also had significantly more frequent PD-L1 expression (67% and 83%, respectively) compared to T1 cancers (48%). There was no correlation between PD-L1 expression and age, nodal status or histology. In multivariate analysis including age, grade, tumor size, histology, nodal status, TIL score and RS, only TIL and RS remained as independent predictors of PDL1 positivity.

Conclusions: Approximately half of early stage ER+ breast cancers were PD-L1+ using the SP142 assay, but expression levels are low with only 14% showing ≥ 5% immune cell staining. PD-L1 expression is significantly more frequent and higher in larger tumors (T2, T3), grade 3 cancers, and in cancers with RS &gt;25. PD-L1 expression also correlates with TIL score but not with histologic type, nodal status or age. These findings suggest that the most chemotherapy sensitive (grade 3, RS&gt; 25), larger ER+ cancers may benefit from immunotherapy added to chemotherapy, similar to triple negative cancers.

n (%)PD-L1 positivePD-L1 negativep-value (Chi-sq)Histology0.9IDC151 (71%)7567ILC53 (25%)2723other9 (4%)54Grade0.02174 (35%)33362110 (53%)5152329 (12%)236Tumor Size0.008T1145 (68%)6374T262 (29%)3919T3/T46 (3%)51Nodal Status0.9N0177 (84%)9077N135 (16%)1716Age (years)range 39-850.8≤5036 (17%)1815&gt;50177 (83%)8979Recurrence Score0.003RS &lt;1180 (37%)3443RS 12-2594 (45%)4543RS &gt;2539 (18%)288TIL Count0.0000008&lt;10%159 (78%)678610-29%30 (15%)263≥30%14 (7%)111PDL1positive (≥1%)107 (53%)negative94 (47%)

Citation Format: Kim RM Blenman, Malini Harigopal, Richard Huang, Emily Reisenbichler, Tao Qing, Eiman Ibrahim, Kamaljeet Singh, Shakti Ramkissoon, Roberts Mustimbo, Jeffrey Ross, Lajos Pusztai. PD-L1 protein expression in relation to Recurrence Score values in early stage ER+HER2- breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-08-03.