GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE324nnn/GSE324721/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE324721GEOGSEfalseNeoadjuvant Palbociclib Treatment Impacts Cell Cycle Progression of DCISBackground. Ductal carcinoma in situ (DCIS) is a non-invasive disease of the breast. This study assessed the impact of the CDK4/6 inhibitor, Palbociclib, on halting cell cycle progression of DCIS between diagnostic biopsy and surgical resection of the lesion. Methods. A dual-arm study was conducted involving 15 patients with DCIS who were given either 100mg palbociclib PO daily for twelve days or no treatment before surgery. FFPE tissues from the diagnostic biopsy and from surgical specimens were analyzed to assess changes due to treatment. Results. Palbociclib treatment significantly reduced Ki67 staining in surgical tissues. Also, RNA-seq analysis comparing the diagnostic biopsy and surgical specimens showed significant downregulation of cellular proliferation pathways after treatment. A cellular deconvolution analysis revealed a treatment-induced decrease in the abundance of mature luminal epithelial cells. Conclusion. We found that short-term treatment with palbociclib before surgical resection was safe and well tolerated in patients. Tissue analysis showed a significant reduction in proliferation markers and downregulation of cell cycle progression genes within DCIS. These results indicate that palbociclib may be effective in the neoadjuvant setting of early stage breast cancer. Trial registration. ClinicalTrials.gov NCT035355062026/09/02GSE324721GSM9583516GSM9583505GSM9583517GSM9583506GSM9583503GSM9583514GSM9583504GSM9583515GSM9583509GSM9583507GSM9583518GSM9583519GSM9583508GSM9583497GSM9583498GSM9583496GSM9583501GSM9583512GSM9583513GSM9583502GSM9583510GSM9583499GSM9583500GSM958351134284324721Homo sapiens[42649946]