RESUMO
PURPOSE: T-cell-mediated cytotoxicity is suppressed when programmed cell death-1 (PD-1) is bound by PD-1 ligand-1 (PD-L1) or PD-L2. Although PD-1 inhibitors have been approved for triple-negative breast cancer, the lower response rates of 25%-30% in estrogen receptor-positive (ER+) breast cancer will require markers to identify likely responders. The focus of this study was to evaluate whether PD-L2, which has higher affinity than PD-L1 for PD-1, is a predictor of early recurrence in ER+ breast cancer. METHODS: PD-L2 protein levels in cancer cells and stromal cells of therapy-naive, localized or locoregional ER+ breast cancers were measured retrospectively by quantitative immunofluorescence histocytometry and correlated with progression-free survival (PFS) in the main study cohort (n = 684) and in an independent validation cohort (n = 273). All patients subsequently received standard-of-care adjuvant therapy without immune checkpoint inhibitors. RESULTS: Univariate analysis of the main cohort revealed that high PD-L2 expression in cancer cells was associated with shorter PFS (hazard ratio [HR], 1.8; 95% CI, 1.3 to 2.6; P = .001), which was validated in an independent cohort (HR, 2.3; 95% CI, 1.1 to 4.8; P = .026) and remained independently predictive after multivariable adjustment for common clinicopathological variables (HR, 2.0; 95% CI, 1.4 to 2.9; P < .001). Subanalysis of the ER+ breast cancer patients treated with adjuvant chemotherapy (n = 197) revealed that high PD-L2 levels in cancer cells associated with short PFS in univariate (HR, 2.5; 95% CI, 1.4 to 4.4; P = .003) and multivariable analyses (HR, 3.4; 95% CI, 1.9 to 6.2; P < .001). CONCLUSION: Up to one third of treatment-naive ER+ breast tumors expressed high PD-L2 levels, which independently predicted poor clinical outcome, with evidence of further elevated risk of progression in patients who received adjuvant chemotherapy. Collectively, these data warrant studies to gain a deeper understanding of PD-L2 in the progression of ER+ breast cancer and may provide rationale for immune checkpoint blockade for this patient group.
Assuntos
Antígeno B7-H1 , Neoplasias de Mama Triplo Negativas , Humanos , Receptor de Morte Celular Programada 1 , Estudos RetrospectivosRESUMO
Pain is a common problem for patients undergoing radiation therapy, exacerbated by inconsistent pain documentation. Free-form templates, pain score prompts, and forcing functions are a hierarchy of constraint systems that can be applied to data entry. This study assessed the impact of incorporating these models into electronic health records on pain documentation rates during 450 on-treatment visits and pain severity of 258 patients with bone metastases and breast and thoracic cancer during radiation therapy. Pain documentation is associated with more robust constraint systems: free form (0.11, 95% CI [0.07, 0.18]), pain score prompts (0.87, 95% CI [0.81, 0.92]), and forcing functions (0.97, 95% CI [0.93, 0.99]). Forcing functions also were associated with improved pain control over the course of radiation treatment for bone metastases compared with pain score prompts (P = .026, nonparametric Kruskal-Wallis). Use of forcing functions correlates with increased pain documentation rates, which contributes to improved pain management.