The immune profile of small HER2-positive breast cancers: a secondary analysis from the APT trial.

BACKGROUND: Previous data suggest that the immune microenvironment plays a critical role in human epidermal growth factor receptor 2 (HER2) -positive breast cancer; however, there is little known about the immune profiles of small HER2-positive tumors. In this study, we aimed to characterize the immune microenvironment of small HER2-positive breast cancers included in the Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer (APT) trial and to correlate the immune markers with pathological and molecular tumor characteristics. PATIENTS AND METHODS: The APT trial was a multicenter, single-arm, phase II study of paclitaxel and trastuzumab in patients with node-negative HER2-positive breast cancer. The study included 406 patients with HER2-positive, node-negative breast cancer, measuring up to 3 cm. Exploratory analysis of tumor infiltrating lymphocytes (TIL), programmed death-ligand 1 (PD-L1) expression (by immunohistochemistry), and immune gene signatures using data generated by nCounter PanCancer Pathways Panel (NanoString Technologies, Seattle, WA), and their association with pathological and molecular characteristics was carried out. RESULTS: Of the 406 patients, 328 (81%) had at least one immune assay carried out: 284 cases were evaluated for TIL, 266 for PD-L1, and 213 for immune gene signatures. High TIL (≥60%) were seen with greater frequency in hormone-receptor (HR) negative, histological grades 2 and 3, as well in HER2-enriched and basal-like tumors. Lower stromal PD-L1 (≤1%) expression was seen with greater frequency in HR-positive, histological grade 1, and in luminal tumors. Both TIL and stromal PD-L1 were positively correlated with 10 immune cell signatures, including Th1 and B cell signatures. Luminal B tumors were negatively correlated with those signatures. Significant correlation was seen among these immune markers; however, the magnitude of correlation did not indicate a monotonic relationship between them. CONCLUSION: Immune profiles of small HER2-positive breast cancers differ according to HR status, histological grade, and molecular subtype. Further work is needed to explore the implication of these findings on disease outcome. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00542451.

Implementation of Fetal and Infant Mortality Review (FIMR): experience from the national Healthy Start program.

OBJECTIVES: The implementation of the Fetal and Infant Mortality Review (FIMR) process was examined as part of the evaluation of the national Healthy Start program, a federal program designed to reduce infant mortality in several communities. The implementation of the FIMR process over the 5-year funding period is described in terms of productivity, barriers and facilitators to implementation, and project expenditures. METHODS: Data were derived from grant continuation applications and personal interviews with program staff to produce a qualitative description. RESULTS: As of the summer of 1996, 14 of the 15 Healthy Start sites in the national evaluation had successfully implemented the FIMR process. Most sites had developed a two-tiered review process for examination of case data in which a review by health and social services professionals was followed by community review. In the period 1993 to 1995, the percentage of fetal and infant deaths reviewed had a median of 34% with a range of 4-79% across the sites at a cost of $600 to $3400 per death reviewed. Recommendations were variably implemented. CONCLUSIONS: The FIMR process provides an important opportunity to contribute to the knowledge base regarding infant mortality in these communities. The process, however, has important logistical requirements and may require substantial financial resources that may affect implementation of confidential inquiries into infant mortality and other health problems.