ABSTRACT
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.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/metabolism , Breast Neoplasms/immunology , Receptor, ErbB-2/metabolism , Tumor Microenvironment/immunology , Aged , B7-H1 Antigen/metabolism , Biomarkers, Tumor/immunology , Breast/immunology , Breast/pathology , Breast/surgery , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Breast Neoplasms/therapy , Chemotherapy, Adjuvant/methods , Disease-Free Survival , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Mastectomy , Middle Aged , Paclitaxel/therapeutic use , Trastuzumab/therapeutic use , Tumor Burden/immunologyABSTRACT
Various techniques for injection into the larynx have been well described, including transoral injection with indirect laryngoscopy or direct laryngoscopy and transcutaneous injection through the thyroid cartilage or cricothyroid membrane. We describe a case not amenable to these techniques, in which entry through the thyrohyoid membrane for injection of cidofovir was successfully performed with a thyrohyoid approach. This technique is described, and comparisons are made with currently available techniques.
