Single Cell Rna Sequencing In Patients With Aggressive Subtypes Of Breast Cancer
Posted Date: Sep 21, 2020
- Investigator: Jun-Lin Guan
- Specialties: Breast Cancer, Surgical Oncology
- Type of Study: Observational/Survey
Breast cancer has a heterogeneous disease presentation, from more indolent hormone receptor (HR) + cancers with 5 year survival rates 89-92% to aggressive clinical and biological subtypes including inflammatory breast cancer, HER2+/HR- breast cancer 83% and triple negative breast cancer (TNBC) 77%. While upfront surgical resection has remained standard of care for the more indolent phenotypes, neoadjuvant chemotherapy (NAC) has become increasingly utilized for more aggressive presentations. One reason for this is due to the excellent response rates seen with NAC, with pathologic complete response (pCR) rates of ~55% in HER2+ patients and 54-60% in TNBC patients. Pathologic complete response has been demonstrated as a surrogate for improved clinical response, with one study demonstrating patients with TNBC who achieved pCR demonstrating no significant difference in OS compared to more indolent non-TNBC subtypes. While these response rates represent a step forward, ~40% of patients who fail to achieve a pCR may demonstrate selection phenotypes resistant to both chemotherapy and immune system surveillance. Analysis of tumor expression profiles using single cellular techniques could represent a novel understanding for targeted treatment. Gene expression profiles investigated with bulk analysis techniques average the expression profiles of a biodiverse tumor microenvironment (TME). Bulk analysis combines the expression profiles of both various “cell types” (including malignant cells, cancer stem cells, immune cells and stromal cells) and different “cell states” (ie. cellular division, cellular stress response). A novel approach to studying this expression intra-tumor heterogeneity (eITH) utilized single cell RNA sequencing (scRNA-seq). Analysis utilizing scRNA-seq has demonstrated a conserved pattern of malignant cells in patients with melanoma , head and neck cancer and even TNBC. Further research has utilized TNBC in human models to demonstrated selection for drug resistant and immune system avoidance following neoadjuvant chemotherapy. The Guan laboratory in the Department of Cancer Biology has utilized breast cancer mouse models with scRNA-seq analysis to evaluate the hierarchical cellular composition of these tumor models. Our study aims to comprehensively evaluate the eITH of tumor samples for aggressive human cancer models utilizing scRNA-seq, focusing on those patients receiving NAC.
Patients With High Risk Breast Lesions Noted On Screening Mammography Or Dominant Lesions Found On Exam Concerning For Breast Cancer. Patients Who Are Treatment Naive Will Be Preferentially Collected. Tissue Will Be Collected At The Time Of Core Needle Biopsy And Again At The Time Of Surgical Resection In Selected Patients.
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