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Several studies have demonstrated that tumor cell-derived RNA is presented in the plasma from breast cancer patients. However, no studies have focused on the detection of plasma erbB2 mRNA in breast cancer. In this study the expression of erbB2 mRNA in the plasma was analyzed in 106 breast cancer patients and 50 healthy subjects by using a nested RT-PCR strategy, and the circulating tumor cells were also detected by using a nested RT-PCR for detection of mammaglobin transcripts in the peripheral blood. Plasma erbB2 mRNA was detectable in 46 (43.3%) breast cancer patients, whereas only 5 normal subjects (10%) were positive in the control group (p = 0.001). The presence of erbB2 mRNA in the plasma was not associated with menopausal status, erbB2 expression in primary tumor tissues, tumor size, histological grade, Ki-67 expression or lymph node involvement, but it exhibited a trend for correlation with increasing tumor stages (p = 0.085), and the presence of erbB2 mRNA in the plasma was significantly associated with negative estrogen receptor (ER) and progesterone receptor (PR) status of the primary tumors (p = 0.031 and 0.026, respectively). Furthermore, in a small subset of 36 breast cancer patients we found the presence of plasma erbB2 mRNA was significantly correlated with the occurrence of circulating tumor cells (p = 0.01). Our study suggests that breast cancer patients with the presence of erbB2 mRNA in the plasma may have a high malignancy or an aggressive phenotype, and frequently detecting plasma erbB2 mRNA may provide a novel approach for monitoring breast cancer progression or response to treatment.