Journal Article
. 2018 Sep;173(1).
doi: 10.1007/s10549-018-4964-y.

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

Hiroji Iwata 1 Norikazu Masuda 2 Yutaka Yamamoto 3 Tomomi Fujisawa 4 Tatsuya Toyama 5 Masahiro Kashiwaba 6 Shoichiro Ohtani 7 Naruto Taira 8 Takehiko Sakai 9 Yoshie Hasegawa 10 Rikiya Nakamura 11 Hiromitsu Akabane 12 Yukiko Shibahara 13 Hironobu Sasano 13 Takuhiro Yamaguchi 13 Kentaro Sakamaki 14 Helen Bailey 15 Diana B Cherbavaz 15 Debbie M Jakubowski 15 Naoko Sugiyama 15 Calvin Chao 15 Yasuo Ohashi 16 
Affiliations
  • PMID: 30242578
  •     36 References
  •     10 citations

Abstract

Purpose: The 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.

Methods: NEOS is a phase 3 clinical trial of hormonal therapy ± adjuvant 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 tumors ≥ 2 cm 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 RS ≥ 31. 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.

Results: Of 295 TransNEOS patients (median age 63 years; median tumor size 25 mm; 66% grade 1), 53.2% had RS < 18, 28.5% had RS18-30, and 18.3% had RS ≥ 31. Clinical response rates were 54% (RS < 18), 42% (RS18-30), and 22% (RS ≥ 31). A higher proportion of patients with RS < 18 had clinical responses (p < 0.001 vs. RS ≥ 31). 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. RS ≥ 31, p = 0.010).

Conclusion: The Recurrence Score test is validated to predict clinical response to neoadjuvant letrozole in postmenopausal patients with ER+, HER2-negative, clinically node-negative breast cancer.

Keywords: Breast cancer; Hormonal therapy; Neoadjuvant; Oncotype DX; Recurrence score.

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