Wang Y et al. (2005) Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet 365: 671–679

Adjuvant systemic therapy is recommended for the prevention of recurrence in most patients with lymph-node-negative breast cancer, but some individuals might not require such aggressive treatment. Wang and colleagues have identified a 'genetic signature' which could help to prevent overtreatment by identifying patients at low risk of distant metastases.

Using microarray technology, Wang et al. analyzed the expression of 22,000 genes in tumor samples from 115 lymph-node-negative breast cancer patients who had not received systemic adjuvant or neoadjuvant therapy. A set of 76 genes was identified, the expression levels of which were correlated with survival free of distant recurrence. Most of these were well-characterized genes and several different functional classes were represented.

Testing the 76-gene profile in an additional 171 patients revealed a sensitivity of 93% and a specificity of 48% for the identification of patients who developed distant metastases within 5 years. The signature remained prognostic when premenopausal and postmenopausal women were analyzed separately, and was also independent of age, tumor size, tumor grade and estrogen-receptor status. Importantly, this also applied to patients with small (10–20 mm) tumors.

On the basis of this analysis, genetic profiling using the 76-gene signature would recommend against unnecessary systemic adjuvant therapy in 48% of low-risk patients. This compares favorably with current guidelines, which result in around 90% of these patients receiving such treatment. If confirmed in further studies, say Wang et al., the genetic signature might rule out needless treatment in a substantial proportion of patients.