Validation of the 21-gene test as a predictor of clinical response to neoadjuvant hormonal therapy for ER+, HER2-negative breast cancer: the TransNEOS study

PurposeThe Recurrence Score test is validated to predict benefit of adjuvant chemotherapy. TransNEOS, a translational study of New Primary Endocrine-therapy Origination Study (NEOS), evaluated whether Recurrence Score results can predict clinical response to neoadjuvant letrozole.MethodsNEOS is a phase 3 clinical trial of hormonal therapyadjuvant chemotherapy for postmenopausal patients with ER+, HER2-negative, clinically node-negative breast cancer, after six months of neoadjuvant letrozole and breast surgery. TransNEOS patients had tumors2cm and archived core-biopsy samples taken before neoadjuvant letrozole and subsequently sent for Recurrence Score testing. The primary endpoint was to evaluate clinical (complete or partial) response to neoadjuvant letrozole for RS<18 versus RS31. Secondary endpoints included evaluation of clinical response and rate of breast-conserving surgery (BCS) by continuous Recurrence Score result, ESR1 and PGR single-gene scores, and ER gene-group score.ResultsOf 295 TransNEOS patients (median age 63years; median tumor size 25mm; 66% grade 1), 53.2% had RS<18, 28.5% had RS18-30, and 18.3% had RS31. Clinical response rates were 54% (RS<18), 42% (RS18-30), and 22% (RS31). A higher proportion of patients with RS<18 had clinical responses (p<0.001 vs. RS31). In multivariable analyses, continuous Recurrence Score result (p<0.001), ESR1 score (p=0.049), PGR score (p<0.001), and ER gene-group score (p<0.001) were associated with clinical response. Recurrence Score group was significantly associated with rate of BCS after neoadjuvant treatment (RS<18 vs. RS31, p=0.010).ConclusionThe Recurrence Score test is validated to predict clinical response to neoadjuvant letrozole in postmenopausal patients with ER+, HER2-negative, clinically node-negative breast cancer.