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21-Gene Recurrence Score for prognosis and prediction of taxane benefit after adjuvant chemotherapy plus endocrine therapy: results from NSABP B-28/NRG Oncology

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Abstract

Background

The 21-gene recurrence score (RS) predicts outcome and benefit from adjuvant chemotherapy benefit in breast cancer patients treated with adjuvant endocrine therapy. In the NSABP B-28 study, we evaluated the 21-gene RS for its prognostic impact and its ability to predict benefit from paclitaxel (P) in node-positive, estrogen receptor-positive (ER+) breast cancer patients treated with adjuvant chemotherapy plus tamoxifen.

Methods

The B-28 trial compared doxorubicin/cyclophosphamide (AC) with AC followed by P in 3060 patients. Tamoxifen for 5 years was also given to patients > 50 years and those < 50 years with ER+ and/or progesterone receptor-positive (PR+) tumors. The present study includes 1065 ER-positive, tamoxifen-treated patients with RS assessment. Median follow-up time was 11.2 years.

Results

In univariate analyses, RS was a significant predictor of outcome. In multivariate analyses, RS remained a significant independent predictor of outcome beyond clinico-pathologic factors, age, and type of surgery (p < 0.001). In the study population (n = 1065), the disease-free survival (DFS) hazard ratio (HR) with adding P to AC was 0.87 (95% CI 0.72–1.05; p = 0.14). RS was not a significant predictor of P benefit: for DFS, HRs for adding P to AC in RS low, intermediate, and high subgroups were 1.01 (95% CI 0.69–1.47; p = 0.99), 0.84 (95% CI 0.62–1.14; p = 0.26), and 0.81 (95% CI 0.60–1.10; p = 0.21), respectively (interaction p = 0.64). Similar findings were observed for the other study endpoints.

Conclusions

RS maintains significant prognostic impact in ER-positive, node-positive patients treated with adjuvant chemotherapy plus tamoxifen. However, RS did not significantly predict benefit from adding paclitaxel to AC chemotherapy. (Trial Registration: PDQ: NSABP-B-28).

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Acknowledgement

Public Health Service Grants U10CA-180868, U10CA-180822, UG1CA-189867, from the National Cancer Institute, Department of Health and Human Services, and from Bristol-Myers Squibb Pharmaceutical Research Institute. The authors thank Barbara C. Good, Ph.D., for editorial assistance with this manuscript.

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Author notes

  1. Deceased: Barry C. Lembersky.

Authors and Affiliations

  1. National Surgical Adjuvant Breast and Bowel Project (NSABP) (NSABP Legacy trials are now a part of the NRG Oncology portfolio), Pittsburgh, PA, USA

    Eleftherios P. Mamounas, Soonmyung Paik, S. Rim Kim, Thomas B. Julian, Barry C. Lembersky, D. Lawrence Wickerham & Norman Wolmark

  2. UF Health Cancer Center at Orlando Health, 1400 S., Orange Avenue, MP 700, Orlando, FL, 32806, USA

    Eleftherios P. Mamounas

  3. NRG Oncology and the University of Pittsburgh, Pittsburgh, PA, USA

    Gong Tang, Qing Liu, Jong-Hyeon Jeong & Joseph P. Costantino

  4. Yonsei University College of Medicine, Seoul, South Korea

    Soonmyung Paik

  5. Genomic Health, Inc, Redwood City, CA, USA

    Frederick L. Baehner, Steven M. Butler, Farid Jamshidian, Diana B. Cherbavaz, Amy P. Sing & Steven Shak

  6. Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA, USA

    Thomas B. Julian, D. Lawrence Wickerham & Norman Wolmark

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  1. Eleftherios P. Mamounas
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Corresponding author

Correspondence to Eleftherios P. Mamounas.

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Conflict of interest

Eleftherios P. Mamounas, MD: GHI, Genentech: Consultant, Speakers’ Bureau; Biotheranostics, GRAIL: Consultant; Roche, Celcuity, Macrogenics: Consultant. Gong Tang, PhD: Consulting from: ExxonMobil Biomedical Science Inc. Frederick L. Baehner, MD: Employee, GHI: Salary and stock. Steven M. Butler, PhD: Prior employee of GHI (Departed Dec, 2014), currently retired. Diana B. Cherbavaz, PhD: GHI Employment and equity. Amy P. Sing, MD: Former employee of GHI, stock ownership. Steven Shak, MD: GHI employee, shareholder. Soonmyung Paik, MD, Qing Liu, Jong-Hyeon Jeong, PhD, Seong-Rim Kim, MD, Farid Jamshidian, PhD, Thomas B. Julian, MD, Barry C. Lembersky, MD, D. Lawrence Wickerham, MD, Joseph P. Costantino, Dr PH, and Norman Wolmark, MD declare that they have no conflict of interest.

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Mamounas, E.P., Tang, G., Paik, S. et al. 21-Gene Recurrence Score for prognosis and prediction of taxane benefit after adjuvant chemotherapy plus endocrine therapy: results from NSABP B-28/NRG Oncology. Breast Cancer Res Treat 168, 69–77 (2018). https://doi.org/10.1007/s10549-017-4550-8

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  • DOI: https://doi.org/10.1007/s10549-017-4550-8

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