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
OBJECTIVE: The racial gap in surgical treatment for early-stage non-small cell lung cancer (NSCLC) has been narrowing at the population level, but it is unknown if this trend persists at the facility level. PATIENTS AND METHODS: We queried the National Cancer Database Participant User File from 2006 to 2016 for patients with stage I NSCLC. Facilities were grouped by type, location, and resection volume. The cumulative surgery rate for Black and White patients in each group was calculated, and an incidence rate difference of receipt of surgery was determined. Logistic regression with estimation of marginal effects was used to assess the probability difference of receiving surgery in Black versus White patients in each year. RESULTS: In total, 315,474 patients were included; 287,585 (91.2%) were White and 27,889 (8.8%) were Black. The surgery rate was greater for White patients (60.2% vs 55.8%, P < .001). For most groups, the surgery disparity narrowed over the study period. The disparity widened in community cancer programs; facilities in the New England, West North Central, and Pacific regions; and the lowest volume facilities. The probability difference for receiving surgery was significantly smaller in 2016 versus 2006 in the Middle Atlantic region and community cancer programs; the difference was unchanged for all other groupings. CONCLUSIONS: Trends in disparities in the use of resection for early-stage NSCLC are not universal across facility groupings. As efforts are made toward addressing racial disparities in surgical care for NSCLC, it will be important to remember that population-level analyses may mask lack of progress in certain facility groups.