Prognostic and predictive value of estrogen receptor 1 expression in completely resected non-small cell lung cancer

Adjuvant chemotherapy (ACT) leads to a modest improvement in survival among patients with completely resected non-small cell lung cancer (NSCLC) but molecular predictors are still rare. Publicly available gene microarray, clinical and follow-up data from two different studies on early-stage NSCLC were used to determine the expression of estrogen receptor 1 (ESR1). Expression values were calculated against clinical and survival data in a training set (n = 138) and a test set (subpopulation from the adjuvant JBR.10 study) allowing the determination of the prognostic effect of ESR1 in the observational arm as well as the predictive effect of ESR1 regarding ACT. Data were well balanced in terms of ESR1 expression. ESR1 high expression was of significant positive prognostic value in the training set and this could be confirmed in the test set cohort (hazard ratio for overall survival 0.248, 95% confidence interval: 0.088-0.701; p = 0.008). Additionally, ESR1 low tumors showed a benefit from ACT in terms of 5-year survival (33.3% observation arm and 77.8% ACT arm; p = 0.003), whereas patients with ESR1 high tumors did not have any benefit from ACT (test of interaction p = 0.024). ESR1 is an independent positive prognostic factor for survival in early-stage NSCLC patients. Patients with ESR1 high tumors did not benefit from ACT. What's new? While non-small cell lung cancer (NSCLC) patients are at a high risk of tumor relapse in spite of curative resection and also adjuvant chemotherapy, some remain relapse-free even with no adjuvant chemotherapy. Prognostic and predictive markers are therefore of utmost importance for an adequate therapeutic strategy. The authors show for the first time that estrogen receptor 1 (ESR1) expression in NSCLC is of prognostic value and might be predictive of the benefit of adjuvant chemotherapy. If the results are confirmed, ESR1 expression could help stratify NSCLC patients into different prognostic groups and inform decision-making regarding the use of adjuvant chemotherapy.