Faculty Bibliography

INTRODUCTION/BACKGROUND:Early lymph node (LN) metastasis often precedes systemic metastasis and corresponds with significantly inferior survival for patients diagnosed with early-stage breast cancer (EBC). To understand the biological pathways involved in early LN metastasis, differential gene expression (DGE) analysis compared large tumors without evidence of LN metastasis (pT2-3pN0) to small tumors with LN metastasis (pT1pN+). METHODS:This study included 2,349 patients with EBC who underwent MammaPrint and BluePrint testing as part of the FLEX (NCT03053193). DGE was performed between pT2-3pN0/pT1pN + and across their MP/BP subtypes. Immune deconvolution was assessed using gene-signature-based methods, complemented by conventional tumor-infiltrating lymphocyte (TIL) analyses on a representative subset of patients. RESULTS:Greater DGE was observed within the MammaPrint High Risk and BluePrint Luminal B subgroups compared to pathological stages. MammaPrint High Risk tumors saw 73 differentially expressed genes (DEGs), while 34 were found for Luminal B tumors. Gene set enrichment analysis (GSEA) of MammaPrint High Risk/Luminal B tumors showed upregulated proliferation pathways and downregulated epithelial-to-mesenchymal transition (EMT) and immune profiles in pT2-3pN0 vs. pT1pN+, respectively. Immune deconvolution analyses showed a higher abundance of T gamma delta cells and CD4 + Th1 cells and a lower abundance of T regulatory cells, M2 macrophages, and cancer-associated fibroblasts within pT2-3pN0 tumors. Conventional histological assessment revealed no significant differences in TILs. CONCLUSION/CONCLUSIONS:This study lays the groundwork for exploring mechanisms of LN metastasis in EBC and their relation to MammaPrint High Risk and Luminal B subtypes. These data support previous studies' association of LN metastasis with EMT and immune dysregulation.

Purpose: Advancements in breast radiation therapy offer innumerable benefits to patients and the health care system. Despite promising outcomes, clinicians remain hesitant about long-term side effects and disease control with accelerated partial breast radiation therapy (APBI). Herein, we review the long-term outcomes of patients with early-stage breast cancer treated with adjuvant stereotactic partial breast irradiation (SAPBI). Methods and Materials: This retrospective study examined outcomes of patients who received diagnoses of early-stage breast cancer treated with adjuvant robotic SAPBI. All patients were eligible for standard ABPI and underwent lumpectomy, followed by fiducial placement in preparation for SAPBI. Using fiducial and respiratory tracking to maintain a precise dose distribution throughout the course of treatment, patients received 30 Gy in 5 fractions on consecutive days. Follow-up occurred at routine intervals to evaluate disease control, toxicity, and cosmesis. Toxicity and cosmesis were characterized using the Common Terminology Criteria for Adverse Events version 5.0 and Harvard Cosmesis Scale, respectively.
Result(s): Patients (N = 50) were a median age of 68.5 years at the time of treatment. The median tumor size was 7.2 mm, 60% had an invasive cell type, and 90% were estrogen receptor positive, progesterone receptor positive, or both. Patients (n = 49) were followed for a median of 4.68 years for disease control and 1.25 years for cosmesis and toxicity. One patient experienced local recurrence, 1 patient experienced grade 3+ late toxicity, and 44 patients demonstrated excellent cosmesis.
Conclusion(s): To our knowledge, this is the largest retrospective analysis with the longest follow-up time for disease control among patients with early breast cancer treated with robotic SAPBI. With follow-up time for cosmesis and toxicity comparable to that of previous studies, results of the present cohort advance our understanding of the excellent disease control, excellent cosmesis, and limited toxicity that can be achieved by treating select patients with early-stage breast cancer with robotic SAPBI.
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IMPLICATIONS/CONCLUSIONS:Tracheal lacerations are rare, but potentially fatal, complications of intubations. Diagnosis of such conditions is difficult, and thus a high level of suspicion must be kept. We present a case and review the literature for factors that indicate high-risk patients.