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A 95-gene signature stratifies recurrence risk of invasive disease in ER-positive, HER2-negative, node-negative breast cancer with intermediate 21-gene signature recurrence scores

  • Epidemiology
  • Published:
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Abstract

Purpose

A subset of patients with intermediate 21-gene signature assay recurrence score may benefit from adjuvant chemoendocrine therapy, but a predictive strategy is needed to identify such patients. The 95-gene signature assay was tested to stratify patients with intermediate RS into high (95GC-H) and low (95GC-L) groups that were associated with invasive recurrence risk.

Methods

Patients with ER-positive, HER2-negative, node-negative breast cancer and RS 11–25 who underwent definitive surgery and adjuvant endocrine therapy without any cytotoxic agents were included. RNA was extracted from archived formalin-fixed, paraffin-embedded samples, and 95-gene signature was calculated.

Results

206 patients had RS of 11–25 (95GC-L, N = 163; 95GC-H, N = 43). In Cox proportional hazards model, 95GC-H was significantly associated with shorter time to recurrence than was 95GC-L (HR 5.94; 95%CI 1.81–19.53; P = 0.005). The correlation between 95-gene signature and 21-gene signature assay scores was not strong (correlation coefficient r = 0.27), which might suggest that 95-gene signature reflects biological characteristics differing from what 21-gene signature shows.

Conclusions

The 95-gene signature stratifies patients with ER-positive, HER2-negative, node-negative invasive breast cancer and intermediate RS of 11–25 into high and low groups that are associated with recurrence risk of invasive disease. Further retrospective analysis in the prospectively accrued TAILORx population is warranted to confirm that 95-gene signature can identify patients who would benefit from adjuvant chemoendocrine therapy.

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Acknowledgements

Editorial assistance was provided by Sunita Patterson and Donald R Norwood of Scientific Publication Services, Research Medical Library, The University of Texas MD Anderson Cancer Center. We also thank Kirk Y. Hirata and Christine Nakamoto of Pathology, The Queen’s Medical Center for collection archival tissue samples.

Funding

This work was supported by the Morgan Welch Inflammatory Breast Cancer Research Program; a Grant from the State of Texas Rare and Aggressive Breast Cancer Research Program; the MD Anderson’s Cancer Center Support Grant from the National Cancer Institute (CA016672).

Author information

Authors and Affiliations

  1. Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA

    Takeo Fujii, Akshara Raghavendra, Arup Kumar Sinha, Jose Rodrigo Espinosa Fernandez, Anjali James, Debu Tripathy & Naoto T. Ueno

  2. Section of Translational Breast Cancer Research, Department of Breast Medical Oncology, Unit 1354, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA

    Takeo Fujii & Naoto T. Ueno

  3. John A. Burns School of Medicine, University of Hawai’i, 651 Ilalo St, Honolulu, HI, 96813, USA

    Takeo Fujii & Jared D. Acoba

  4. University of Hawai’i Cancer Center, 701 Ilalo St, Honolulu, HI, 96813, USA

    Takeo Fujii, Robert Schuetz & Jared D. Acoba

  5. Department of Breast Surgical Oncology, Showa University, 1-5-8 Hatanodai Shinagawa-ku, Tokyo, 142-8666, Japan

    Hiroko Masuda, Yuki Matsunaga & Seigo Nakamura

  6. Division of Hematology and Oncology, Medical College of Wisconsin, 9200 W Wisconsin Ave, Milwaukee, WI, 53226, USA

    Yee Chung Cheng

  7. Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA

    Fei Yang

  8. Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA

    Aysegul A. Sahin

  9. Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita-shi, Osaka, 565-0871, Japan

    Yasuto Naoi & Shinzaburo Noguchi

  10. Sysmex Corporation, 1-5-1, Wakinohama-kaigandori, Chuo-ku, Kobe, Hyogo, 651-0073, Japan

    Keisuke Yamagishi, Tomoko Matsushima & Sachiyo Tada

  11. Anne Arundel Medical Center, Rebecca Fortney Breast Center, 2000 Medical Pkwy, Annapolis, MD, 21401, USA

    Rubie S. Jackson

  12. Hyogo Prefectural Nishinomiya Hospital, 13-9, Rokutanjicho, Nishinomiya, Hyogo, 662-0918, Japan

    Shinzaburo Noguchi

Authors
  1. Takeo Fujii
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  2. Hiroko Masuda
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  3. Yee Chung Cheng
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  4. Fei Yang
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  5. Aysegul A. Sahin
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  6. Yasuto Naoi
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  11. Anjali James
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  14. Robert Schuetz
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  15. Debu Tripathy
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  19. Seigo Nakamura
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  20. Jared D. Acoba
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  21. Naoto T. Ueno
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Corresponding author

Correspondence to Naoto T. Ueno.

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Conflict of interest

K.Y., T.M., and S.T. are employees of Sysmex Corporation (Curebest™ 95GC Breast service provider). Y.N. holds a joint patent on Curebest™ 95GC Breast with Sysmex Corporation, receive research funds from Sysmex and AstraZeneca, and received a lecture fee of 100,000 yen a year from Sysmex Corporation, AstraZeneca and Takeda. S.N. has received honoraria and research grants from Sysmex Corporation and has been an advisor for Sysmex Corporation and holds a joint patent on Curebest™ 95GC Breast with Sysmex. N.T.U. has research grants with Sysmex Corporation and with Genomic Health.

Ethical approval

This retrospective chart review with linked tissue analysis was approved by the central Institutional Review Boards at the five participating institutions in the USA and Japan: The University of Texas MD Anderson Cancer Center (protocol number: PA15-0905), University of Hawai’i Cancer Center (protocol number: RA-2017-021), Medical College of Wisconsin (protocol number: PRO00029366), Anne Arundel Medical Center (protocol number: 1056834), and Showa University (protocol number: 2383). A waiver of informed consent was granted based on the study’s retrospective nature.

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Fujii, T., Masuda, H., Cheng, Y.C. et al. A 95-gene signature stratifies recurrence risk of invasive disease in ER-positive, HER2-negative, node-negative breast cancer with intermediate 21-gene signature recurrence scores. Breast Cancer Res Treat 189, 455–461 (2021). https://doi.org/10.1007/s10549-021-06276-7

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  • DOI: https://doi.org/10.1007/s10549-021-06276-7

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