Breast Cancer Biomarker Predicts Disease Progression

Researchers have identified a biomarker on breast cancer cells that is indicative of the severity of the disease and may forecast the outcome of chemotherapy.

The biomarker is the transcription factor signal transducer and activator of transcription-5 (Stat5). Stat proteins are a direct link from the receptor to the nucleus. Inactive Stat proteins in the cytoplasm are recruited directly to the receptor on cytokine stimulation, which leads to phosphorylation and dimerization. Then the activated Stat dimers travel to the nucleus, where they bind to specific sequences in the promoters of target genes and mediate gene transcription. Stat5 has been theorized to be the physiologic substrate of the insulin receptor. In knockout mice lacking Stat5, no hematopoietic development was impaired; however, Stat5 alpha-deficient female mice failed to lactate due to impairment of mammary development. Stat5 has been shown to be the essential mediator of prolactin induced milk protein gene activation.

Investigators at Georgetown University Medical Center (Washington, DC, USA) measured Stat 5 levels in three large groups of tissues from patients with breast cancer and from normal controls. Immunohistochemical analyses were performed on specimens from over 1,100 patients, giving the study a solid statistical basis.

The authors reported in the June 1, 2004, issue of the Journal of Clinical Oncology that Stat5 activation, but not Stat5 protein expression, was gradually lost during cancer progression, with detectable activation in 100% of healthy breast specimens compared with less than 20% of node-positive breast cancers and metastases. Stat5 activation in tumors was associated with favorable prognosis. Stat5 activation remained an independent prognostic marker after adjusting for patient age, tumor size, histologic grade, estrogen receptor, progesterone receptor, and Her2/neu status. Moreover, the assay for Stat5 is simple, inexpensive, and can be rapidly adapted to routine analysis in pathology laboratories using standard procedures.

"Detection of the Stat5 marker in early stage breast cancer may lead to improved individualized therapy,” said senior author Dr. Hallgeir Rui, associate professor of oncology at Georgetown University. "This may include more careful follow-up and more aggressive treatment of patients at higher risk of breast cancer recurrence, and reduced treatment in patients with excellent prognosis.”



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