Immediate Gene Expression Changes After the First Course of Neoadjuvant Chemotherapy in Patients with Primary Breast Cancer Disease

Abstract

Purpose: Our goal was to identify genes undergoing expressional changes shortly after the beginning of neoadjuvant chemotherapy for primary breast cancer.Experimental Design: The biopsies were taken from patients with primary breast cancer prior to any treatment and 24 hours after the beginning of the neoadjuvant chemotherapy. Expression analyses from matched pair samples representing 25 patients were carried out with Clontech filter arrays. A subcohort of those 25 paired samples were additionally analyzed with the Affymetrix GeneChip platform. All of the transcripts from both platforms were queried for expressional changes.Results: Performing hierarchical cluster analysis, we clustered pre-and posttreatment samples from individual patients more closely to each other than the samples taken from different patients. This reflects the rather low number of transcripts responding directly to the drugs used. Although transcriptional drug response occurring during therapy differed between individual patients, two genes (p21 WAF1/CIP1 and MIC-1) were up-regulated in posttreatment samples. This could be validated by semiquantitative and real-time reverse transcription-PCR. Partial leastdiscriminant analysis based on approximately 25 genes independently identified by either Clontech or Affymetrix platforms could clearly discriminate pre-and posttreatment samples. However, correlation of certain gene expression levels as well as of differential patterns and clusters as determined by a different platform was not always satisfying.Conclusions: This study has demonstrated the potential of monitoring posttreatment changes in gene expression as a measure of the pharmacodynamics of drugs. As a clinical laboratory model, it can be useful to identify patients with sensitive and reactive tumors and to help for optimized choice for sequential therapy and obviously improve relapsefree and overall survival.

Enriched variations in TEKT4 and breast cancer resistance to paclitaxel

“…Although NCT is effective in reducing the size of the primary tumour before surgery, residual disease after NCT is common and is associated with a higher risk of metastatic recurrence compared with patients achieving pathologic complete remission 12 . The altered gene-expression profiles of breast cancer under NCT have been described [13][14][15] . Recent studies using nextgeneration sequencing to analyse residual breast cancer after NCT identified diverse pathway activation in drug-resistant tumour cells 16 .…”

Prostate-derived factor—a novel inhibitor of drug-induced cell death in colon cancer cells

“…Consistent with our findings, PDF overexpression is involved in resistance to cisplatin (22) as well as in docetaxel and mitoxantrone resistance (23). In addition, PDF was reported as one of two genes consistently up-regulated in biopsies from breast cancer patients after treatment with epirubicin/cyclophosphamide and epirubicin/Taxol (46).…”

Analysis of gene expression identifies PLAB as a mediator of the apoptotic activity of fenretinide in human ovarian cancer cells

“…Therefore, the role of the observed PLAB upmodulation in 4-HPR activity cannot be ruled out. Interestingly, PLAB induction in humans has been observed following neoadiuvant therapy in breast cancer biopsies and also in that case, the correlation with response to therapy was not known (Modlich et al, 2004).…”