A four-gene predictive model of clinical response to aromatase inhibitors in breast cancer by 2 weeks has been generated and validated by researchers at the University of Edinburgh Cancer Research UK Centre in Edinburgh, Scotland, and colleagues, a new study published online ahead of print in the Journal of Clinical Oncology has shown.

Because response rates to neoadjuvant aromatase inhibitors are only 50% to 70% and lower in patients with advanced disease, accurate biomarkers to predict patients who would benefit from adjuvant aromastase inhibitor therapy are needed.

For the study, researchers characterized the molecular response to letrozole and developed a four-gene classifier of clinical response. These four genes are IL6STNGFRAP1ASPMMCM4.

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In a blinded, independent validation data set of patients with breast cancer treated with adjuvant anastrozole, the four-gene predictive model was found to be 91% accurate.

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Results showed that matched 2-week on-treatment biopsies were associated with improved predictive power compared with pretreatment biopsies alone.

The study also demonstrated that the four-gene signature significantly predicted recurrence-free survival (P=0.029) and breast cancer-specific survival (P=0.009).


  1. Turnbull AK, Arthur LM, Renshaw L, et al. Accurate prediction and validation of response to endocrine therapy in breast cancer. J Clin Oncol. 2015. [Epub ahead of print]. doi: 10.1200/JCO.2014.57.8963.