Using pretreatment biopsies of oestrogen receptor-negative (ER−) breast tumours, Farmer et al. have shown that a stromal gene signature can predict resistance to neoadjuvant chemotherapy.
Pretreatment biopsies were taken from 63 patients enrolled in the randomized Phase III European Organisation for Research and Treatment of Cancer (EORTC) 10994 trial; these patients were from the treatment arm that received 5-fluorouracil, epirubicin and cyclophosphamide (FEC) prior to surgery. The majority (84.1%) of tumours had ductal histology; 6.3% were lobular and 9.5% were not assessable. Conventional techniques were unable to predict the response of these patients to FEC, so the authors developed a new strategy examining clusters of coexpressed genes related to nine specific cell types and biological processes: stroma, T cells, B cells, adipocytes, luminal–basal cells, apocrine cells, proliferation, hypoxia and interferon signaling. A representative gene for each process or cell type was chosen, and the model was fitted using an external data set comprising 581 tumour samples from the Netherlands Cancer Institute (NKI) and Erasmus Medical Center (EMC). The authors chose 50 genes with the strongest association to each of the 9 representative genes in the NKI-EMC data set. They then averaged the expression data from the EORTC data set for the 50 genes to generate a metagene, comprising a single value, for each of the 9 processes or cell types.
