ABSTRACT
OBJECTIVE: This retrospective study aimed to explore the clinical efficacy of palbociclib with endocrine therapy (ET) in women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer in real-world practice. PATIENTS AND METHODS: This retrospective study analyzed the medical records of patients to determine treatment outcomes. Progression-free survival (PFS) curves were generated using log-rank tests with the Kaplan-Meier method. Treatment outcomes in Chinese patients were compared with those in patients from the USA, Argentina, Canada, and Europe in the IRIS study. RESULTS: In total, 69 patients were included in this study. The median PFS was 12.8 months (95% confidence interval: 10.1-15.5). A longer PFS was observed for patients with bone-only metastases, no liver metastases, no previous palliative chemotherapy, no previous palliative ET, and ET sensitivity. The overall response rate was 10.1%, and the clinical benefit rate was 78.3%. Nineteen patients (27.5%) received a reduced dose of palbociclib according to the decision of their physicians. Dose reduction did not affect the clinical efficacy of the combined treatment. Compared with those in the IRIS study, Chinese patients receiving palbociclib-based treatment were younger, and they had fewer bone-only metastases and more visceral and liver metastases. The clinical benefit rate and overall response rate for Chinese patients were lower than those observed for the patients in the IRIS study. CONCLUSIONS: ET combined with palbociclib treatment was effective and well-tolerated in HR+/HER2- metastatic breast cancer patients in the real-world setting. Earlier use of palbociclib-ET was associated with more clinical benefits in HR+/HER2- metastatic breast cancer.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Asian People , Breast Neoplasms/drug therapy , Adult , Age Factors , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/pathology , Cohort Studies , Dose-Response Relationship, Drug , Female , Humans , Middle Aged , Piperazines/administration & dosage , Progression-Free Survival , Pyridines/administration & dosage , Receptor, ErbB-2/metabolism , Retrospective Studies , Treatment OutcomeABSTRACT
PNRC (Proline-rich Nuclear Receptor Coactivator) is a novel coactivator for multiple nuclear receptors. PNRC was previously identified using bovine SF-1 (steroidogenic factor 1) as the bait in a yeast two-hybrid screening of a human mammary gland cDNA expression library. To understand the molecular mechanisms that regulate the expression of human PNRC gene, in this study, functional analysis of the 5' flanking region of the human PNRC gene revealed that the -123/+27 region is the minimal promoter of the human PNRC gene. Gel shift and ChIP analyses demonstrated the specific binding of RFX1 (Regulatory Factor X) protein to the human PNRC promoter region. In co-transfection experiments RFX1 was shown to repress promoter activity of PNRC gene in a dose-dependent manner. These results indicate that r RFX1 specifically bind to promoter region and negatively regulate the transcription of the human PNRC gene.
