Expression profiling to predict postoperative prognosis for estrogen receptor‐negative breast cancers by analysis of 25,344 genes on a cDNA microarray

Estrogen receptor (ER) status is an essential determinant of clinical and biological behavior of human breast cancers. While ER‐positive breast cancers respond well to adjuvant hormone therapy, ER‐negative tumors are generally resistant. To date, no attempts have succeeded in finding molecular markers for classifying ER‐negative breast cancers with respect to postoperative prognosis. To identify a set of prognostic markers for this type of cancer, we used a cDNA microarray consisting of 25,344 human genes to investigate expression profiles of ten primary breast cancers from patients who had died of breast cancer within 5 years after surgery (5y‐D) and 10 from patients who had survived disease‐free for more than 5 years (5y‐S). Sets of genes characterizing each group were identified by Mann‐Whitney and random‐permutation tests. We documented 71 genes with higher expression in the 5y‐D group than in the 5y‐S group, and 15 with higher expression in the 5y‐S group than in the 5y‐D group. Semi‐quantitative RT‐PCR experiments were carried out to confirm the results of the microarray analysis. We established a scoring system for predicting postoperative prognosis of ER‐negative breast cancers on the basis of aberrant gene expression. The list of genes reported here provides valuable information with regard to progression of breast cancer and is a source of possible target molecules for development of novel drugs to treat patients with ER‐negative breast cancers.