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William J. Gradishar, MD, FACP, FASCO
William J. Gradishar, MD, FACP, FASCO
Posted: Monday, April 22, 2024
The NEOLETEXE trial, a phase II study, enrolled 102 postmenopausal patients with locally advanced breast cancer, focusing on comparing letrozole and exemestane, aromatase inhibitors used in managing estrogen receptor (ER)-positive breast cancer. The study, conducted by Vessela N. Kristensen, PhD, of University of Oslo, Institute of Clinical Medicine, and colleagues aimed to assess the evolutionary trajectories of cancer and immune cells during treatment, employing single-cell DNA and RNA sequencing at baseline, crossover, and after treatment. These findings, which were presented at the American Association for Cancer Research (AACR) Annual Meeting 2024 (Abstract LB394/11), may shed light on the underlying factors contributing to the sensitivity and resistance to aromatase inhibitors.
Using the Mission Bio Tapestri Platform, the study investigators designed a custom panel for single-cell DNA sequencing, validating 81% of clusters defined by whole-exome sequencing. Single-nucleus analysis enabled identification of mutations and copy number variations, revealing clonal development during treatment. Furthermore, single-cell RNA analysis distinguished between normal and malignant epithelial cells. The study examined immune cell types, including CD4, CD8, natural killer cells, and macrophages, to delineate their differentiation trajectories through RNA velocity and diffusion pseudotime.
The findings yielded a detailed map of diverse clones and cell types present in NEOLETEXE trial tumor biopsies, providing insights into therapy’s impact on cancer and immune cell evolution. Of note, the study elucidated factors contributing to sensitivity and resistance to aromatase inhibitors, which the authors noted are crucial for optimizing treatment strategies in patients with ER-positive breast cancer.
Overall, the NEOLETEXE trial’s single-cell analyses offer a comprehensive understanding of tumor and immune cell dynamics during neoadjuvant aromatase inhibitors therapy. This high-resolution view highlights the complexity of tumor evolution and immune responses, informing future clinical decisions in ER-positive breast cancer management.
Disclosure: The study authors reported no conflicts of interest.
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