A subset of breast cancer patients (14% of our data set) neoadjuvantly treated with epirubicin-based chemotherapy experience complete remission associated with prolonged survival. Based on massively parallel transcriptome analysis, we describe for the first time early in situ effects of epirubicin-based chemotherapy in a neoadjuvant setting. We took jet-needle biopsies from 22 individual tumors immediately before and 24 h after the first cycle of chemotherapy. Clontech's 1.2 human cancer complementary DNA arrays were used. Jet-needle biopsies (30 mm3) yielded sufficient material (20–60 μg total RNA) for gene expression profiling. Of 1,185 genes selected for the array 30–50% were expressed. The most prominent early effect of chemotherapy was an upregulation of the cyclin kinase inhibitor WAF1, an important regulator of the G1–S transition in 82% of the tumors (average induction 2.8-fold; range 1.5- to 7-fold). Of the other cyclin kinase inhibitors, only p16-INK4A and p57-KIP2 were upregulated in a small subset of tumors. We observed a moderate chemotherapy-induced upregulation of various DNA repair enzymes. This group included XPC, an initiator of global genome nucleotide excision repair; endonuclease III homologue 1 (HNTH1) and DNA-damage-inducible transcript 3 (DDIT3, GADD153). Preliminary supervised cluster analysis seems to be encouraging for response prediction. Jet-needle technology is appropriate for in situ response monitoring in neoadjuvantly treated breast cancer patients. Chemotherapy-induced effects on cell-cycle control and DNA repair could be demonstrated as early as 24 hrs after the onset of therapy.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bojar, H., Prisack, H., Modlich, O. et al. In situ monitoring of early effects of epirubicin-based neoadjuvant chemotherapy in breast cancer by cDNA array technology. Nat Genet 27 (Suppl 4), 44 (2001). https://doi.org/10.1038/87012
Issue Date:
DOI: https://doi.org/10.1038/87012