The role of programmed death ligand-1 and tumor-infiltrating lymphocytes in breast cancer overexpressing HER2 gene.

PURPOSE: The purpose of the study is to investigate the prognostic significance of programmed death ligand-1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) in HER2+ breast cancer (BC). METHODS: HER2+ BC cases (n  = 191) were collected between 1996 and 2013. Tissue microarray (TMA) slides were stained with two clones of PD-L1 antibodies (28-8 and 22C3) and the percentage of positive membranous staining was scored. TILs of the full sections were also scored using percentage scale. RESULTS: Clone 28-8 had expression in ≥ 1% of the tumor cells in 25.7% of the cases, while clone 22C3 in ≥ 1% of the tumor cells was expressed in 11.5% of the cases. In the multivariate analysis, higher expression of PD-L1 (clone 28-8) in tumor correlated with lower risk of tumor recurrence, with HR of 0.4 (p = 0.033). Higher level of TILs (> 15%) predicts better overall survival (OS) in all patients with HR of 0.35 (p  = 0.0046). In the group of patients who were treated with trastuzumab-based adjuvant chemotherapy, lower PD-L1 (clone 28-8) expression in TILs correlated with tumor recurrence (p  = 0.034). In the group of patients who were treated with non-trastuzumab-based adjuvant chemotherapy, lower TILs and lower PD-L1 (clone 28-8) expression in tumor had borderline statistical significance in association with tumor recurrence (p  = 0.064 and 0.083, respectively). In the group of patients who were treated with trastuzumab-based adjuvant chemotherapy, PD-L1 or TILs was not statistically significant to predict 5-year survival. In the group of patients who were treated with non-trastuzumab-based adjuvant chemotherapy, low TILs (p = 0.009) correlated with 5-year death due to disease. CONCLUSION: We conclude that PD-L1 may have prognostic significance in HER2+ BCs.

Metaplastic Carcinoma of the Breast Is More Aggressive Than Triple-negative Breast Cancer: A Study From a Single Institution and Review of Literature.

BACKGROUND: We aimed to describe our experience with metaplastic breast carcinoma (MBC), evaluate its clinical outcome compared with triple-negative breast cancer (TNBC), and provide a through and comprehensive review of the literature to date. MATERIALS AND METHODS: We reviewed MBC cases (n = 46) from our institution. The following variables were recorded: tumor histologic subtype, Nottingham grade, tumor size, lymph node status, Tumor, Node, Metastases stage, biomarkers profile, patient's age and race, therapy modality (chemotherapy and radiation), and survival (disease-free survival [DFS] and overall survival [OS]). The clinical and pathological data for TNBC (n = 508) cases were extracted from the breast cancer database. To compare the survival between MBC and TNBC, a subgroup of MBC cases (n = 40) were matched with TNBC cases (n = 40) on the basis of known prognostic confounders. RESULTS: There were 17 of 46 (37%) cases with mesenchymal differentiation, 12 (26.1%) squamous cell carcinoma, 14 (30.4%) spindle cell carcinoma, and 3 (6.5%) mixed type. MBC presented at a more advanced stage than TNBC (P = .014) and was more likely to recur (34% vs. 15.5%; P = .004). More MBC patients died from disease than TNBC (29% vs. 16%; P = .05). In the multivariate analysis, MBC had approximately twice the risk of local recurrence than TNBC (95% confidence interval, 1.01-3.83; P = .05). MBC patients had worse DFS and OS than the matched TNBC patients (P < .001 and P = .033, respectively). A review of the literature comparing MBC versus TNBC is presented. CONCLUSION: Our results suggest that MBC is clinically more aggressive than TNBC. Further studies might help delineate the differences between these 2 entities.