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Breast Cancer Research and Treatment

, Volume 143, Issue 3, pp 485–492 | Cite as

Central pathology laboratory review of HER2 and ER in early breast cancer: an ALTTO trial [BIG 2-06/NCCTG N063D (Alliance)] ring study

  • Ann E. McCulloughEmail author
  • Patrizia Dell’Orto
  • Monica M. Reinholz
  • Richard D. Gelber
  • Amylou C. Dueck
  • Leila Russo
  • Robert B. Jenkins
  • Stefania Andrighetto
  • Beiyun Chen
  • Christian Jackisch
  • Michael Untch
  • Edith A. Perez
  • Martine J. Piccart-Gebhart
  • Giuseppe Viale
Clinical trial

Abstract

Choice of therapy for breast cancer relies on human epidermal growth factor receptor-2 (HER2) and estrogen receptor α (ER) status. Before randomization in the phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation (ALTTO) trial for HER2-positive disease, HER2 and ER were centrally reviewed by Mayo Clinic (Rochester, MN, and Scottsdale, AZ) for North America and by the European Institute of Oncology (IEO; Milan, Italy) for the rest of world (except China). Discordance rates (local vs. central review) differed between Mayo and IEO. Among locally HER2-positive cases, 5.8 % (Mayo) and 14.5 % (IEO) were centrally HER2 negative. Among locally ER-positive cases, 16.2 % (Mayo) and 4.2 % (IEO) were centrally ER-negative. Among locally ER-negative cases, 3.4 % (Mayo) and 21.4 % (IEO) were centrally ER-positive. We, therefore, performed a ring study to identify features contributing to these differing discordance rates. Mayo and IEO exchanged slides for 25 HER2 and 35 ER locally/centrally discordant cases. Both laboratories performed IHC and FISH for HER2 using the HercepTest® and PathVysion HER2 DNA probe kit/HER2/centromere 17 probe mixture. IHC for ER was tested centrally using the monoclonal ER 1D5 antibody (Mayo) or the DAKO cocktail of ER 1D5 and 2.123 antibodies (IEO). Mayo and IEO confirmed the central HER2-negative result in 100 % of 25 cases. Mayo and IEO confirmed the central ER result in 29 (85 %) of 34 evaluable cases. The five Mayo-negative/IEO-positive cases were ER-positive when retested at Mayo using the DAKO ER cocktail. In this ring study, ALTTO ineligibility did not change when HER2 testing was performed by either IEO or Mayo central laboratories. However, a dual antibody ER assay had fewer false-negative test results than an assay with a single antibody, and there was more discordance between the two ER reagents than has been previously reported. Using even slightly different assay methods yielded different results, even between experienced central laboratories.

Keywords

Breast cancer Estrogen receptor testing HER2 testing Central laboratory review Local versus central laboratory concordance 

Notes

Acknowledgments

This work was supported by NIH/NCI Grant, U24 CA114740 (PI: JC Buckner).

Ethical standards

The ALTTO trial as well as the ring study reported in this manuscript comply with the current laws of the countries in which they were performed.

Conflict of interest

Dr. Richard D. Gelber received research support from GSK. Dr. Christian Jackisch received research support from Roche and GSK. All other authors declare that they have no conflict of interest.

Supplementary material

10549_2013_2827_MOESM1_ESM.docx (50 kb)
Supplementary material 1 (DOCX 50 kb)

References

  1. 1.
    Perez EA, Romond EH, Suman VJ et al (2011) Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: joint analysis of data from NCCTG N9831 and NSABP B-31. J Clin Oncol 29:3366–3373PubMedCrossRefGoogle Scholar
  2. 2.
    Viale G, Regan MM, Maiorano E et al (2007) Prognostic and predictive value of centrally reviewed expression of estrogen and progesterone receptors in a randomized trial comparing letrozole and tamoxifen adjuvant therapy for postmenopausal early breast cancer: BIG 1-98. J Clin Oncol 25:3846–3852PubMedCrossRefGoogle Scholar
  3. 3.
    Wolff AC, Hammond ME, Schwartz JN et al (2007) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 25:118–145PubMedCrossRefGoogle Scholar
  4. 4.
    Hammond ME, Hayes DF, Dowsett M et al (2010) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version). Arch Pathol Lab Med 134:e48–e72PubMedGoogle Scholar
  5. 5.
    Dako product insert for Dako ER/PR pharmDX kit for the Dako Autostainer, edition 10/11Google Scholar
  6. 6.
    Phillips T, Murray G, Wakamiya K et al (2007) Development of standard estrogen and progesterone receptor immunohistochemical assays for selection of patients for antihormonal therapy. Appl Immunohistochem Mol Morphol (AIMM) 15:325–331CrossRefGoogle Scholar
  7. 7.
    Dowsett M, Hanna WM, Kockx M et al (2007) Standardization of HER2 testing: results of an international proficiency-testing ring study. Mod Pathol 20:584–591PubMedCrossRefGoogle Scholar
  8. 8.
    Perez EA, Press MF, Dueck AC et al (2013) Immunohistochemistry and fluorescence in situ hybridization assessment of HER2 in clinical trials of adjuvant therapy for breast cancer (NCCTG N9831, BCIRG 006, and BCIRG 005). Breast Cancer Res Treat 138:99–108PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Wolff AC, Hammond EH, Hicks DG et al (2013) Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline update. J Clin Oncol 31:3997–4013Google Scholar
  10. 10.
    Perez EA, Dueck AC, McCullough AE et al (2012) Predictability of adjuvant trastuzumab benefit in N9831 patients using the ASCO/CAP HER2-positivity criteria. J Natl Cancer Inst 104:159–162PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Ann E. McCullough
    • 1
    Email author
  • Patrizia Dell’Orto
    • 2
  • Monica M. Reinholz
    • 3
  • Richard D. Gelber
    • 4
    • 5
  • Amylou C. Dueck
    • 1
  • Leila Russo
    • 2
  • Robert B. Jenkins
    • 6
  • Stefania Andrighetto
    • 2
  • Beiyun Chen
    • 6
  • Christian Jackisch
    • 7
  • Michael Untch
    • 8
  • Edith A. Perez
    • 9
  • Martine J. Piccart-Gebhart
    • 10
  • Giuseppe Viale
    • 2
  1. 1.Department of Laboratory Medicine and PathologyMayo Clinic ArizonaScottsdaleUSA
  2. 2.European Institute of OncologyUniversity of MilanMilanItaly
  3. 3.Ventana Medical SystemsTucsonUSA
  4. 4.Department of Biostatistics and Computational Biology, Dana-Farber Cancer InstituteMailstop CLSB 11007BostonUSA
  5. 5.Frontier Science and Technology Research FoundationBostonUSA
  6. 6.Mayo ClinicRochesterUSA
  7. 7.Klinikum OffenbachOffenbachGermany
  8. 8.HELIOS Klinikum Berlin BuchBerlinGermany
  9. 9.Mayo ClinicJacksonvilleUSA
  10. 10.Institut Jules BordetUniversité Libre de BruxellesBrusselsBelgium

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