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

摘要

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 RS18 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 RS18, 28.5 had RS18-30, and 18.3 had RS31. Clinical response rates were 54 (RS18), 42 (RS18-30), and 22 (RS31). A higher proportion of patients with RS18 had clinical responses (p0.001 vs. RS31). In multivariable analyses, continuous Recurrence Score result (p0.001), ESR1 score (p=0.049), PGR score (p0.001), and ER gene-group score (p0.001) were associated with clinical response. Recurrence Score group was significantly associated with rate of BCS after neoadjuvant treatment (RS18 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.