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Breast Cancer Research and Treatment

, Volume 165, Issue 3, pp 573–583 | Cite as

Reducing chemotherapy use in clinically high-risk, genomically low-risk pN0 and pN1 early breast cancer patients: five-year data from the prospective, randomised phase 3 West German Study Group (WSG) PlanB trial

  • Ulrike Nitz
  • Oleg Gluz
  • Matthias Christgen
  • Ronald E. Kates
  • Michael Clemens
  • Wolfram Malter
  • Benno Nuding
  • Bahriye Aktas
  • Sherko Kuemmel
  • Toralf Reimer
  • Andrea Stefek
  • Fatemeh Lorenz-Salehi
  • Petra Krabisch
  • Marianne Just
  • Doris Augustin
  • Cornelia Liedtke
  • Calvin Chao
  • Steven Shak
  • Rachel Wuerstlein
  • Hans H. Kreipe
  • Nadia Harbeck
Clinical trial

Abstract

Background

The prospective phase 3 PlanB trial used the Oncotype DX® Recurrence Score® (RS) to define a genomically low-risk subset of clinically high-risk pN0-1 early breast cancer (EBC) patients for treatment with adjuvant endocrine therapy (ET) alone. Here, we report five-year data evaluating the prognostic value of RS, Ki-67, and other traditional clinicopathological parameters.

Methods

A central tumour bank was prospectively established within PlanB. Following an early amendment, hormone receptor (HR)+ , pN0-1 RS ≤ 11 patients were recommended to omit chemotherapy. Patients with RS ≥ 12, pN2-3, or HR-negative/HER2-negative disease were randomised to anthracycline-containing or anthracycline-free chemotherapy. Primary endpoint: disease-free survival (DFS). PlanB Clinicaltrials.gov identifier: NCT01049425.

Findings

From 2009 to 2011, PlanB enrolled 3198 patients (central tumour bank, n = 3073) with the median age of 56 years, 41.1% pN+, and 32.5% grade 3 EBC. Chemotherapy was omitted in 348/404 (86.1%) eligible RS ≤ 11 patients. After 55 months of median follow-up, five-year DFS in ET-treated RS ≤ 11 patients was 94% (in both pN0 and pN1) versus 94% (RS 12–25) and 84% (RS > 25) in chemotherapy-treated patients (p < 0.001); five-year overall survival (OS) was 99 versus 97% and 93%, respectively (p < 0.001). Nodal status, central/local grade, tumour size, continuous Ki-67, progesterone receptor (PR), IHC4, and RS were univariate prognostic factors for DFS. In a multivariate analysis including all univariate prognostic markers, only pN2-3, central and local grade 3, tumour size >2 cm, and RS, but not IHC4 or Ki-67 were independent adverse factors. If RS was excluded, IHC4 or both Ki-67 and PR entered the model. The impact of RS was particularly pronounced in patients with intermediate Ki-67 (>10%, <40%) tumours.

Interpretation

The excellent five-year outcomes in clinically high-risk, genomically low-risk (RS ≤ 11) pN0-1 patients without adjuvant chemotherapy support using RS with standardised pathology for treatment decisions in HR+ HER2-negative EBC. Ki-67 has the potential to support patient selection for genomic testing.

Keywords

Genomic signature Oncotype DX Breast cancer Ki-67 IHC4 

Notes

Acknowledgements

The study was supported by Genomic Health Inc, Sanofi Aventis, and Amgen. Medical editing support was provided by Avital Bareket-Samish, PhD, and funded by Genomic Health Inc. We thank all the study centres, patients, and pathologists for providing study materials. We also thank the teams of the WSG, Palleos, and central pathology lab at the MHH for their work.

Funding

Genomic Health Inc, Sanofi Aventis, and Amgen.

Compliance with ethical standards

Conflict of interest

HK received honoraria from Roche, Genomic Health, Novartis, and Astra-Zeneca. The West German Study group provided grant for central pathology work (to HK). RW received honoraria from Roche, Celgene, Novartis, Genomic Health, Amgen, MSD, Pfizer, and Pierre Fabre. NH received honoraria from Genomic Health, Nanostring and, Agendia. OG received honoraria from Genomic Health, Nanostring, and Roche. UN (as a representative of the WSG) received grants from Genomic Health, Sanofi Aventis, and Amgen for the conduct of the trial and received honoraria from Genomic Health, Agendia, Nanostring, Amgen, and Sanofi Aventis. CL and SK received honoraria from Genomic Health. All the other authors (TR, MJ, MC, MC) have declared that they have no conflict of interest. SS is an employee and a shareholder of Genomic Health (SS patent rights assigned to Genomic Health). CC is an employee of Genomic Health. All the other authors had nothing to disclose.

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Ulrike Nitz
    • 1
    • 2
  • Oleg Gluz
    • 1
    • 2
  • Matthias Christgen
    • 3
  • Ronald E. Kates
    • 1
  • Michael Clemens
    • 4
  • Wolfram Malter
    • 5
  • Benno Nuding
    • 6
  • Bahriye Aktas
    • 7
  • Sherko Kuemmel
    • 8
  • Toralf Reimer
    • 9
  • Andrea Stefek
    • 10
  • Fatemeh Lorenz-Salehi
    • 11
  • Petra Krabisch
    • 12
  • Marianne Just
    • 13
  • Doris Augustin
    • 14
  • Cornelia Liedtke
    • 1
    • 15
  • Calvin Chao
    • 16
  • Steven Shak
    • 16
  • Rachel Wuerstlein
    • 1
    • 17
  • Hans H. Kreipe
    • 3
  • Nadia Harbeck
    • 1
    • 17
  1. 1.West German Study GroupMoenchengladbachGermany
  2. 2.Ev. Hospital BethesdaBreast Center NiederrheinMoenchengladbachGermany
  3. 3.Institute of PathologyMedical School HannoverHannoverGermany
  4. 4.Department of OncologyClinics Mutterhaus der BorromäerinnenTrierGermany
  5. 5.Department of Gynecology and ObstetricsBreast Center, University Clinics CologneCologneGermany
  6. 6.Department of Gynecology and ObstetricsEvangelical HospitalBergisch GladbachGermany
  7. 7.Department of Gynecology and ObstetricsUniversity Clinics EssenEssenGermany
  8. 8.Clinics Essen-MitteBreast CentreEssenGermany
  9. 9.Department of Gynecology and ObstetricsClinics SuedstadtRostockGermany
  10. 10.Johanniter Clinics StendalBreast Center AltmarkStendalGermany
  11. 11.Department of GynecologyDr. Horst-Schmidt ClinicsWiesbadenGermany
  12. 12.Klinikum ChemnitzFlemmingstraße 2ChemnitzGermany
  13. 13.Oncological PracticeBielefeldGermany
  14. 14.Breast Centre OstbayernDeggendorfGermany
  15. 15.Department of Gynecology and ObstetricsUniversity Hospital Schleswig–Holstein Campus LuebeckLuebeckGermany
  16. 16.Genomic Health, Inc.Redwood CityUSA
  17. 17.Department of Gynecology and ObstetricsBreast Center, University of Munich (LMU) and CCCLMUMunichGermany

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