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Neoadjuvant Palbociclib Treatment Impacts Cell Cycle Progression of DCIS
Rohith Battina1, Candace Mainor2, Marcel O Schmidt1
1Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA.
Abstract:
Background. 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 in DCIS between diagnostic biopsy and surgical resection of the lesion. Methods. A dual-arm study was conducted involving 17 participants with DCIS who were given either 100 mg of 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. RNA-seq analysis comparing the diagnostic biopsy and surgical specimens showed significant downregulation of cellular proliferation pathways after treatment. A cellular deconvolution analysis demonstrated a non-significant trend of a treatment-induced decrease in the abundance of mature luminal epithelial cells. Conclusions. Short-term palbociclib monotherapy before surgical resection was safe and well tolerated in participants. Tissue analysis showed a significant reduction in proliferation markers and the downregulation of cell cycle progression genes within DCIS. These results support further investigation of palbociclib in patients with DCIS. Trial registration. ClinicalTrials.gov NCT03535506.
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