PD-L1 expression in breast invasive ductal carcinoma with incomplete pathological response to neoadjuvant chemotherapy

Abstract

Objectives: To investigate the expression of programmed death-ligand 1 (PD-L1) in breast cancer in association with incomplete pathological response (PR) to neoadjuvant chemotherapy (NAC). Methods PD-L1 expression was evaluated using immunohistochemistry in post-operative, post-NAC samples of 60 patients ( n = 60) diagnosed with breast invasive ductal carcinoma with incomplete PR to NAC, including 31 matched pre-NAC and post-NAC samples ( n = 31). PD-L1 protein expression was assessed using three scoring approaches, including the tumor proportion score (TPS), the immune cell score (ICS), and the combined tumor and immune cell score (combined positive score, CPS) with a 1% cut-off. Results In the post-operative, post-NAC samples ( n = 60), positive expression rate of PD-L1 was observed in 18.3% (11/60) of cases by TPS, 31.7% (19/60) by ICS, and 25% (15/60) by CPS. In matched samples, positive expression rate of PD-L1 was observed in 19.3% (6/31) of patients by TPS, 51.6% (16/31) by ICS, and 19.3% (6/31) by CPS in pre-NAC specimens, while it was observed in 22.6% (7/31) of matched post-NAC samples by TPS, 22.6% (7/31) by ICS, and 19.3% (6/31) by CPS. In the matched samples, there was a significant decrease in PD-L1 immunoexpression using ICS in post-NAC specimens (McNemar’s, p = 0.020), while no significant differences were found using TPS and CPS between pre- and post-NAC samples ( p = 1.000, p = 0.617; respectively). PD-L1 immunoexpression determined by TPS or CPS was only significantly associated with ER status ( p = 0.022, p = 0.021; respectively), but not with other clinicopathological variables. We could not establish a correlation between PD-L1 expression and the overall survival rate ( p > 0.05). There were no significant differences in the tumor infiltrating lymphocytes count between the paired pre- and post-NAC samples ( t = 0.581, p = 0.563 or Wilcoxon’s Signed Rank test; z = -0.625, p = 0.529). Conclusion Our findings indicate that PD-L1 protein expression in infiltrating immune cells was significantly reduced in breast tumors that developed incomplete PR following the exposure to NAC.

Predictive Role of Peripheral Blood Lymphocyte And Cytokine Phenotypes in Patients with Operable Breast Cancer And Neoadjuvant Therapy: A Preliminary Study

“…Higher expression of PD-L1 on tumor cells was associated with the higher rates of pathologic complete response to durvalumab and chemotherapy [21] . In addition, PD-L1 expression was also associated with better pathological responses to NAT [22,23] , even to BC patients [24,25] . After NAT, PD-L1 expression on tumor cells was reported to be associated with tumor load and characteristics [26] .…”

Characterization of BCL-XL, MCL-1, and BAX Protein Expression in Response to Neoadjuvant Chemotherapy in Breast Cancer

“…Immunohistochemistry (IHC) was performed as described previously 32–36 . Briefly, 4 µm tissue sections were placed on clean adhesive/positively charged glass slides (TOMO Adhesive Microscope Slides, Matsunami, Japan) by floated them from a 45°C water bath.…”

“…Immunohistochemistry (IHC) was performed as described previously. [32][33][34][35][36] Briefly, 4 µm tissue sections were placed on clean adhesive/positively charged glass slides (TOMO Adhesive Microscope Slides, Matsunami, Japan) by floated them from a 45°C water bath. Tissue sections were dried for 30 minutes at 65°C before being dewaxed with xylene twice for 5 minutes each time, then rehydrated using declining alcohol-graded solutions (100%, 95%, and 70% ethanol; 3 min each) followed by being washed in deionized water.…”

The Emerging Role of Tertiary Lymphoid Structures in Breast Cancer: A Narrative Review

“…Diagnosing TLSs in the tumor microenvironment is a complex task due to various factors, including the heterogeneity of TLSs and the tumoral microenvironment. For example, the evaluation of PD-L1 expression, a commonly used biomarker, is susceptible to high inter-observer variability due to the use of different antibodies, platforms, and scoring systems [54,55]. When selecting tissue for TLS diagnosis, it is crucial to acknowledge that these structures exhibit spatial variations within tumor tissues and may not be fully represented when in small-needle biopsy samples or tissue microarrays.…”