Comparison of three scoring methods using the FDA-approved 22C3 immunohistochemistry assay to evaluate PD-L1 expression in breast cancer and their association with clinicopathologic factors

Abstract

Background: In the evaluation of PD-L1 expression to select patients for anti-PD-1/PD-L1 treatment, uniform guidelines that account for different immunohistochemistry assays, different cell types and different cutoff values across tumor types are lacking. Data on how different scoring methods compare in breast cancer are scant. Methods: Using FDA-approved 22C3 diagnostic immunohistochemistry assay, we retrospectively evaluated PD-L1 expression in 496 primary invasive breast tumors that were not exposed to anti-PD-1/PD-L1 treatment and compared three scoring methods (TC: invasive tumor cells; IC: tumor-infiltrating immune cells; TCIC: a combination of tumor cells and immune cells) in expression frequency and association with clinicopathologic factors. Results: In the entire cohort, positive PD-L1 expression was observed in 20% of patients by TCIC, 16% by IC, and 10% by TC, with a concordance of 87% between the three methods. In the triple-negative breast cancer patients, positive PD-L1 expression was observed in 35% by TCIC, 31% by IC, and 16% by TC, with a concordance of 76%. Associations between PD-L1 and clinicopathologic factors were investigated according to receptor groups and whether the patients had received neoadjuvant chemotherapy. The three scoring methods showed differences in their associations with clinicopathologic factors in all subgroups studied. Positive PD-L1 expression by IC was significantly associated with worse overall survival in patients with neoadjuvant chemotherapy and showed a trend for worse overall survival and distant metastasis-free survival in triple-negative patients with neoadjuvant chemotherapy. Positive PD-L1 expression by TCIC and TC also showed trends for worse survival in different subgroups.

Prognostic Role of PD-L1 Expression in Invasive Breast Cancer: A Systematic Review and Meta-Analysis

“…A total of 22 articles were included in this study [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ]. Most of the studies were retrospective, and the follow-up interval varied from 3 months to 15 years.…”

“…Ten studies evaluated the association between PD-L1 expression and survival in women with IBC [ 19 , 22 , 23 , 25 , 26 , 28 , 29 , 39 , 40 , 41 ] ( Table 3 ). Of these, five studies determined OS [ 22 , 28 , 29 , 39 , 40 ], and five studies evaluated DFS [ 20 , 23 , 25 , 26 , 41 ]. Of these, three studies found that PD-L1 expression was associated with OS using Kaplan–Meier curves [ 22 , 39 , 40 ].…”

Currently Used Laboratory Methodologies for Assays Detecting PD-1, PD-L1, PD-L2 and Soluble PD-L1 in Patients with Metastatic Breast Cancer

“…Lastly, the combined positive score involves both TC and IC located in the TC or the narrow rim around the TC. The number of PD-L1-positive TCs and ICs was counted, relative to the number of all vital TCs, and then multiplied by 100 [102,104]. These scoring methods were associated with the adopted clones.…”

Molecular Biomarkers for Contemporary Therapies in Hormone Receptor-Positive Breast Cancer

“…Over-expression of PD-L1 in cancer is thought to co-opt this mechanism, leading to immune system evasion, one of the modern hallmarks of cancer [ 114 ]. While its expression by IHC analysis can be utilised as a biomarker in breast cancer, there is no consensus about assay choice; cut-off; or measuring tumour cells, immune cells, or both [ 115 ]. One study using modified Histo-score with a positive cut-off ≥ 100 found 23% of 650 evaluable breast cases to be PD-L1+, as well as an association with worse prognosis, both in the overall cohort and the HER2-negative luminal B subset [ 116 ].…”