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Clinical Trial
. 2019 Jan;173(1):123-133.
doi: 10.1007/s10549-018-4964-y. Epub 2018 Sep 21.

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
Clinical Trial

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 et al. Breast Cancer Res Treat. 2019 Jan.

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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Conflict of interest statement

Conflict of interest

Hiroji Iwata: Remuneration: AstraZeneca, Chugai, Daiichi-Sankyo, Eisai, Genomic Health, Novartis, Pfizer, Taiho. Consultant/advisory role: AstraZeneca, Chugai, Daiichi-Sankyo, Kyowa Hakko Kirin, Lilly, Novartis, Pfizer. Funding: AstraZeneca, Bayer, Chugai, Daiichi-Sankyo, Eisai, GSK, Kyowa Hakko Kirin, Lily, MSD, Novartis, Pfizer. Other: CSPOR BC organizing committee member. Norikazu Masuda: Remuneration: AstraZeneca, Chugai, Pfizer, Takeda. Funding to institution: AstraZeneca, Chugai, Daiichi-Sankyo, Kyowa Hakko Kirin, Lilly, MSD, Novartis, Pfizer. Yutaka Yamamoto: Remuneration: AstraZeneca, Chugai, Daiichi-Sankyo, Eisai, Genomic Health, Kyowa Hakko Kirin, Novartis, Pfizer, Taiho, Takeda. Funding: AstraZeneca, Chugai, Novartis, Taiho. Tatsuya Toyama: Remuneration: AstraZeneca, Chugai, Daiichi-Sankyo, Eisai, Ono Pharmaceutical, Taiho, Takeda. Funding: AstraZeneca, Chugai, Daiichi-Sankyo, Eisai, Kyowa Hakko Kirin, Nippon Kiyaku, Novartis, Pfizer, Taiho, Takeda. Masahiro Kashiwaba: Remuneration: AstraZeneca, Chugai, Kyowa Hakko Kirin, Novartis, Pfizer. Shoichiro Ohtani: Remuneration: Chugai, Eisai. Tomomi Fujisawa, Naruto Taira, Takehiko Sakai, Yoshie Hasegawa, Rikiya Nakamura, Hiromitsu Akabane, Yukiko Shibahara, and Hironobu Sasano: None. Takuhiro Yamaguchi: Remuneration: Daiichi-Sankyo. Consulting or advisory role: CAC Croit Corporation, Chugai, Daiichi-Sankyo, Japan Tobacco, Kowa Company, Ono Pharmaceutical, Tsumura & Co. Funding: A2 Healthcare Corporation, AC Medical Inc., CAC Croit Corporation, Daiichi-Sankyo, FMD K&L Japan K.K., Japan Media Corporation, Japan Tobacco Inc., Kyowa Hakko Kirin, Luminary Medical K.K., Medidata Solutions, Inc., Ono Pharmaceutical. Kentaro Sakamaki: Remuneration: Chugai, Novartis, Taiho. Travel expenses: Genomic Health. Helen Bailey: Employment and stock ownership: Genomic Health. Diana B. Cherbavaz: Stock ownership: Genomic Health. Debbie M. Jakubowski: Employment and stock ownership: Genomic Health. Naoko Sugiyama: Employment and stock ownership: Genomic Health. Calvin Chao: Employment and stock ownership: Genomic Health. Yasuo Ohashi: Remuneration: Daiichi-Sankyo, Eisai, Public Health Research Foundation, Sanofi. Research grant: Eisai. Consultant/advisory role: Chugai, Kowa, Taiho. Travel expenses: Takeda, Yakult Honsha. Other: Shionogi, Statcom.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was reviewed and approved by each institution’s review board and/or ethics committee.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Figures

Fig. 1
Fig. 1
REMARK diagram
Fig. 2
Fig. 2
Percent clinical response to neoadjuvant letrozole by Recurrence Score Group (N = 295); CR complete response, PD progressive disease, PR partial response, RS Recurrence Score, SD stable disease
See this image and copyright information in PMC

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