Intratumor spatial heterogeneity in programmed death-ligand 1 (PD-L1) protein expression in early-stage breast cancer.

PURPOSE: Programmed death-ligand 1 (PD-L1) expression is required for benefit from immune checkpoint inhibitors in metastatic triple negative breast cancer (TNBC). In contrast, in the neoadjuvant setting patients benefited regardless of PD-L1 expression. We hypothesized that, in stages II-III breast cancers, low levels of PD-L1 expression may be sufficient to confer sensitivity to therapy and focal expression could be missed by a biopsy. METHODS: In this study, we examined intratumor spatial heterogeneity of PD-L1 protein expression in multiple biopsies from different regions of breast cancers in 57 primary breast tumors (n = 33 TNBC, n = 19 estrogen receptor-positive [ER-positive], n = 5 human epidermal receptor 2-positive [HER2 +]). E1L3N antibody was used to assess PD-L1 status and staining was scored using the combined positivity score (CPS) with PD-L1 positive defined as CPS ≥ 10. RESULTS: Overall, 19% (11/57) of tumors were PD-L1 positive based on positivity in at least 1 biopsy. Among TNBC, PD-L1 positivity was 27% (9/33). The discordance rate, defined as the same tumor yielding PD-L1 positive and negative samples in different regions, was 16% (n = 9) in the whole study population and 23% (n = 7) in TNBC. Cohen's kappa coefficient of agreement was 0.214 for the whole study and 0.239 for TNBC, both of which falling into a non-statistically significant fair agreement range. Among all PD-L1 positive cases, 82% (n = 9/11) had positivity in only one of the tissue assessments. CONCLUSION: These results indicate that the overall 84% concordance is driven by concordant negative results. In PD-L1 positive cancers, within-tumor heterogeneity in PD-L1 expression exists.

Survival in Women with De Novo Metastatic Breast Cancer: A Comparison of Real-World Evidence from a Publicly-Funded Canadian Province and the United States by Insurance Status.

Metastatic breast cancer (MBC) patient outcomes may vary according to distinct health care payers and different countries. We compared 291 Alberta (AB), Canada and 9429 US patients < 65 with de novo MBC diagnosed from 2010 through 2014. Data were extracted from the provincial Breast Data Mart and from the National Cancer Institute's SEER program. US patients were divided by insurance status (US privately insured, US Medicaid or US uninsured). Kaplan-Meier and log-rank analyses were used to assess differences in OS and hazard ratios (HR) were estimated using Cox models. Multivariate models were adjusted for age, surgical status, and biomarker profile. No difference in OS was noted between AB and US patients (HR = 0.92 (0.77-1.10), p = 0.365). Median OS was not reached for the US privately insured and AB groups, and was 11 months and 8 months for the US Medicaid and US uninsured groups, respectively. The 3-year OS rates were comparable between US privately insured and AB groups (53.28% (51.95-54.59) and 55.54% (49.49-61.16), respectively). Both groups had improved survival (p < 0.001) relative to the US Medicaid and US uninsured groups [39.32% (37.25-41.37) and 40.53% (36.20-44.81)]. Our study suggests that a universal health care system is not inferior to a private insurance-based model for de novo MBC.