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Impact of the updated 2018 ASCO/CAP guidelines on HER2 FISH testing in invasive breast cancer: a retrospective study of HER2 fish results of 2233 cases

  • Zhi-Hua Liu
  • Kun Wang
  • Dan-Yi Lin
  • Jie Xu
  • Jie Chen
  • Xiao-Yu Long
  • Yan Ge
  • Xin-Lan Luo
  • Ke-Ping Zhang
  • Yan-Hui Liu
  • Fang-Ping XuEmail author
Preclinical study
  • 57 Downloads

Abstract

Objectives

Human epidermal growth factor receptor 2 (HER2, ERBB2) is a valuable prognostic and predictive biomarker in breast cancer. Accurate assessment of HER2 status is essential in selecting the patients with invasive breast cancer who will likely response to HER2-targeted therapies. Some major modifications in the diagnostic recommendation for fluorescence in situ hybridization (FISH) have been made in the updated 2018 American Society of Clinical Oncology (ASCO)/College of American Pathologist (CAP) guideline. According to the revised guideline, concomitant IHC assays are required to arrive at the most accurate HER2 status designation after HER2 FISH equivocal results; however, little is known about its influence on the clinical practice of pathologist. The purpose of this study was to evaluate the impact of the revised 2018 ASCO/CAP guidelines on the HER2 status designation.

Methods

We retrospectively reviewed the HER2 FISH testing results from 2233 cases of invasive breast cancer between January 2014 and December 2017. Concomitant immunohistochemistry (IHC) were performed on the same tissue blocks that were used for the FISH testing.

Results

Compared to the 2013 guidelines, the HER2 status in 183 (8.2%) cases were re-defined when reassessed by the 2018 guidelines. Among these 183 cases, 175 equivocal cases according to the 2013 guideline were re-defined as HER2 negative (n = 173) or HER2 positive (n = 2). Eight previously classified as HER2 positive cases were converted to negative in the 2018 scheme, all of which were with HER2 IHC scores of 1+ or 2+. The number of cases in the negative category was 1705 according to the 2018 guidelines as opposed to 1524 by the 2013 guidelines.

Conclusions

The updated 2018 ASCO/CAP guidelines eliminated the FISH equivocal category, which can be attributed to reflex HER2 IHC, and partly ease the dilemma for clinical practice. Reflex IHC for FISH equivocal cases is of prime importance; furthermore, HER2 FISH results were converted from positivity to negativity based on the concomitant IHC results in a small percentage of cases. In all, implementation of the 2018 ASCO/CAP guidelines provides much clearer instructions and recommendations for the HER2 status designation, and thus reduces the risk of misdiagnosis.

Keywords

Breast cancer HER2 Immunohistochemistry Fluorescence in situ hybridization ASCO/CAP guidelines 

Abbreviations

HER2

Human epidermal growth factor 2

IHC

Immunohistochemistry

FISH

Fluorescence in situ hybridization

ASCO

American Society of Clinical Oncology

CAP

College of American Pathologists

Notes

Acknowledgements

We thank Hui–Hui Jiang for outstanding technical support and Zhi Li for constructive comments on the manuscript.

Funding

This study is supported by a grant from National Clinical Key Subject Construction Project Fund of China, and grant from Guangdong Medical Science and Technology Research Fund (No. A2016086).

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

All procedures performed involving human participants were in accordance with the ethical standards of the Institutional Review Board of Guangdong General Hospital, Guangdong Academy of Medical Sciences and with the 1964 Helsinki declaration and its later amendments.

Informed consent

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

References

  1. 1.
    McPherson K, Steel CM, Dixon JM (2000) ABC of breast diseases. Breast cancer-epidemiology, risk factors, and genetics. BMJ 321:624–628CrossRefGoogle Scholar
  2. 2.
    Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, van de Vijver M, Wheeler TM, Hayes DF, American Society of Clinical Oncology/College of American P (2007) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med 131:18–43.  https://doi.org/10.1043/1543-2165(2007)131%5B18:ASOCCO%5D2.0.CO;2 Google Scholar
  3. 3.
    Adamczyk A, Kruczak A, Harazin-Lechowska A, Ambicka A, Grela-Wojewoda A, Domagala-Haduch M, Janecka-Widla A, Majchrzyk K, Cichocka A, Rys J, Niemiec J (2018) Relationship between HER2 gene status and selected potential biological features related to trastuzumab resistance and its influence on survival of breast cancer patients undergoing trastuzumab adjuvant treatment. Onco Targets Ther 11:4525–4535.  https://doi.org/10.2147/OTT.S166983 CrossRefGoogle Scholar
  4. 4.
    Cooke T, Reeves J, Lannigan A, Stanton P (2001) The value of the human epidermal growth factor receptor-2 (HER2) as a prognostic marker. Eur J Cancer 37(Suppl 1):S3–S10CrossRefGoogle Scholar
  5. 5.
    Curigliano G, Viale G, Bagnardi V, Fumagalli L, Locatelli M, Rotmensz N, Ghisini R, Colleoni M, Munzone E, Veronesi P, Zurrida S, Nole F, Goldhirsch A (2009) Clinical relevance of HER2 overexpression/amplification in patients with small tumor size and node-negative breast cancer. J Clin Oncol 27:5693–5699.  https://doi.org/10.1200/JCO.2009.22.0962 CrossRefGoogle Scholar
  6. 6.
    Press MF, Bernstein L, Thomas PA, Meisner LF, Zhou JY, Ma Y, Hung G, Robinson RA, Harris C, El-Naggar A, Slamon DJ, Phillips RN, Ross JS, Wolman SR, Flom KJ (1997) HER-2/neu gene amplification characterized by fluorescence in situ hybridization: poor prognosis in node-negative breast carcinomas. J Clin Oncol 15:2894–2904.  https://doi.org/10.1200/JCO.1997.15.8.2894 CrossRefGoogle Scholar
  7. 7.
    Rosen PP, Lesser ML, Arroyo CD, Cranor M, Borgen P, Norton L (1995) Immunohistochemical detection of HER2/neu in patients with axillary lymph node negative breast carcinoma. A study of epidemiologic risk factors, histologic features, and prognosis. Cancer 75:1320–1326CrossRefGoogle Scholar
  8. 8.
    Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177–182CrossRefGoogle Scholar
  9. 9.
    Dang C, Iyengar N, Datko F, D’Andrea G, Theodoulou M, Dickler M, Goldfarb S, Lake D, Fasano J, Fornier M, Gilewski T, Modi S, Gajria D, Moynahan ME, Hamilton N, Patil S, Jochelson M, Norton L, Baselga J, Hudis C (2015) Phase II study of paclitaxel given once per week along with trastuzumab and pertuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol 33:442–447.  https://doi.org/10.1200/JCO.2014.57.1745 CrossRefGoogle Scholar
  10. 10.
    Frenel JS, Bourbouloux E, Berton-Rigaud D, Sadot-Lebouvier S, Zanetti A, Campone M (2009) Lapatinib in metastatic breast cancer. Womens Health (Lond) 5:603–612.  https://doi.org/10.2217/whe.09.54 CrossRefGoogle Scholar
  11. 11.
    Ji G, Zhang C, Guan S, Yao X (2018) Erlotinib for Progressive Brain and Leptomeningeal Metastases From HER2-positive Breast Cancer After Treatment Failure With Trastuzumab and Lapatinib: Experience and Review of Literature. Clin Breast Cancer.  https://doi.org/10.1016/j.clbc.2018.07.022 Google Scholar
  12. 12.
    Rastogi P (2010) Targeting alternative pathways in HER2-positive breast cancer. Oncology (Williston Park) 24:415–416Google Scholar
  13. 13.
    Schoffski P, Cresta S, Mayer IA, Wildiers H, Damian S, Gendreau S, Rooney I, Morrissey KM, Spoerke JM, Ng VW, Singel SM, Winer E (2018) A phase Ib study of pictilisib (GDC-0941) in combination with paclitaxel, with and without bevacizumab or trastuzumab, and with letrozole in advanced breast cancer. Breast Cancer Res 20:109.  https://doi.org/10.1186/s13058-018-1015-x CrossRefGoogle Scholar
  14. 14.
    Urruticoechea A, Rizwanullah M, Im SA, Ruiz ACS, Lang I, Tomasello G, Douthwaite H, Badovinac Crnjevic T, Heeson S, Eng-Wong J, Munoz M (2017) Randomized Phase III Trial of Trastuzumab Plus Capecitabine With or Without Pertuzumab in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer Who Experienced Disease Progression During or After Trastuzumab-Based Therapy. J Clin Oncol 35:3030–3038.  https://doi.org/10.1200/JCO.2016.70.6267 CrossRefGoogle Scholar
  15. 15.
    Pathmanathan N, Bilous AM (2012) HER2 testing in breast cancer: an overview of current techniques and recent developments. Pathology 44:587–595.  https://doi.org/10.1097/PAT.0b013e328359cf9a CrossRefGoogle Scholar
  16. 16.
    Tubbs RR, Hicks DG, Cook J, Downs-Kelly E, Pettay J, Hartke MB, Hood L, Neelon R, Myles J, Budd GT, Moore HC, Andresen S, Crowe JP (2007) Fluorescence in situ hybridization (FISH) as primary methodology for the assessment of HER2 Status in adenocarcinoma of the breast: a single institution experience. Diagn Mol Pathol 16:207–210.  https://doi.org/10.1097/PDM.0b013e318064c72a CrossRefGoogle Scholar
  17. 17.
    Ramakrishna N, Temin S, Chandarlapaty S, Crews JR, Davidson NE, Esteva FJ, Giordano SH, Gonzalez-Angulo AM, Kirshner JJ, Krop I, Levinson J, Modi S, Patt DA, Perez EA, Perlmutter J, Winer EP, Lin NU (2014) Recommendations on disease management for patients with advanced human epidermal growth factor receptor 2-positive breast cancer and brain metastases: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 32:2100–2108.  https://doi.org/10.1200/JCO.2013.54.0955 CrossRefGoogle Scholar
  18. 18.
    Wolff AC, Hammond MEH, Allison KH, Harvey BE, Mangu PB, Bartlett JMS, Bilous M, Ellis IO, Fitzgibbons P, Hanna W, Jenkins RB, Press MF, Spears PA, Vance GH, Viale G, McShane LM, Dowsett M (2018) Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. J Clin Oncol 36:2105–2122.  https://doi.org/10.1200/JCO.2018.77.8738 CrossRefGoogle Scholar
  19. 19.
    Liu YH, Xu FP, Rao JY, Zhuang HG, Luo XL, Li L, Luo DL, Zhang F, Xu J (2009) Justification of the change from 10 to 30% for the immunohistochemical HER2 Scoring criterion in breast cancer. Am J Clin Pathol 132:74–79.  https://doi.org/10.1309/AJCPG3LCVKPNFJ6R CrossRefGoogle Scholar
  20. 20.
    Xu FP, Wang K, Xu J, Chen J, Zhang YF, Wu HM, Zhang MH, Long XX, Luo XL, Zhang KP, Lin DY, Liu YH (2017) Impact of repeat HER2 testing after initial equivocal HER2 FISH results using 2013 ASCO/CAP guidelines. Breast Cancer Res Treat 166:757–764.  https://doi.org/10.1007/s10549-017-4479-y CrossRefGoogle Scholar
  21. 21.
    Bartlett JM, Munro AF, Dunn JA, McConkey C, Jordan S, Twelves CJ, Cameron DA, Thomas J, Campbell FM, Rea DW, Provenzano E, Caldas C, Pharoah P, Hiller L, Earl H, Poole CJ (2010) Predictive markers of anthracycline benefit: a prospectively planned analysis of the UK National Epirubicin Adjuvant Trial (NEAT/BR9601). Lancet Oncol 11:266–274.  https://doi.org/10.1016/S1470-2045(10)70006-1 CrossRefGoogle Scholar
  22. 22.
    Gaiser T, Ruschoff J, Moll R (2012) [In situ hybridization in clinical pathology. Significance of polysomy 17 for HER2 determination and genetic tumor heterogeneity in breast cancer]. Pathologe 33(Suppl 2):307–310.  https://doi.org/10.1007/s00292-012-1663-z CrossRefGoogle Scholar
  23. 23.
    Hofmann M, Stoss O, Gaiser T, Kneitz H, Heinmoller P, Gutjahr T, Kaufmann M, Henkel T, Ruschoff J (2008) Central HER2 IHC and FISH analysis in a trastuzumab (Herceptin) phase II monotherapy study: assessment of test sensitivity and impact of chromosome 17 polysomy. J Clin Pathol 61:89–94.  https://doi.org/10.1136/jcp.2006.043562 CrossRefGoogle Scholar
  24. 24.
    Dent S, Verma S, Latreille J, Rayson D, Clemons M, Mackey J, Verma S, Lemieux J, Provencher L, Chia S, Wang B, Pritchard K (2009) The role of HER2-targeted therapies in women with HER2-overexpressing metastatic breast cancer. Curr Oncol 16:25–35CrossRefGoogle Scholar
  25. 25.
    Ellis IO, Dowsett M, Bartlett J, Walker R, Cooke T, Gullick W, Gusterson B, Mallon E, Lee PB (2000) Recommendations for HER2 testing in the UK. J Clin Pathol 53:890–892CrossRefGoogle Scholar
  26. 26.
    Furrer D, Jacob S, Caron C, Sanschagrin F, Provencher L, Diorio C (2017) Concordance of HER2 immunohistochemistry and fluorescence in situ hybridization using tissue microarray in breast cancer. Anticancer Res 37:3323–3329.  https://doi.org/10.21873/anticanres.11701 Google Scholar
  27. 27.
    Hyeon J, Cho SY, Hong ME, Kang SY, Do I, Im YH, Cho EY (2017) NanoString nCounter(R) approach in breast cancer: a comparative analysis with quantitative real-time polymerase chain reaction, in situ hybridization, and immunohistochemistry. J Breast Cancer 20:286–296.  https://doi.org/10.4048/jbc.2017.20.3.286 CrossRefGoogle Scholar
  28. 28.
    Varga Z, Noske A, Ramach C, Padberg B, Moch H (2013) Assessment of HER2 status in breast cancer: overall positivity rate and accuracy by fluorescence in situ hybridization and immunohistochemistry in a single institution over 12 years: a quality control study. BMC Cancer 13:615.  https://doi.org/10.1186/1471-2407-13-615 CrossRefGoogle Scholar
  29. 29.
    Jimenez RE, Wallis T, Tabasczka P, Visscher DW (2000) Determination of Her-2/Neu status in breast carcinoma: comparative analysis of immunohistochemistry and fluorescent in situ hybridization. Mod Pathol 13:37–45.  https://doi.org/10.1038/modpathol.3880007 CrossRefGoogle Scholar
  30. 30.
    Hanna WM, Ruschoff J, Bilous M, Coudry RA, Dowsett M, Osamura RY, Penault-Llorca F, van de Vijver M, Viale G (2014) HER2 in situ hybridization in breast cancer: clinical implications of polysomy 17 and genetic heterogeneity. Mod Pathol 27:4–18.  https://doi.org/10.1038/modpathol.2013.103 CrossRefGoogle Scholar
  31. 31.
    Marchio C, Lambros MB, Gugliotta P, Di Cantogno LV, Botta C, Pasini B, Tan DS, Mackay A, Fenwick K, Tamber N, Bussolati G, Ashworth A, Reis-Filho JS, Sapino A (2009) Does chromosome 17 centromere copy number predict polysomy in breast cancer? A fluorescence in situ hybridization and microarray-based CGH analysis. J Pathol 219:16–24.  https://doi.org/10.1002/path.2574 CrossRefGoogle Scholar
  32. 32.
    Singh K, Tantravahi U, Lomme MM, Pasquariello T, Steinhoff M, Sung CJ (2016) Updated 2013 College of American Pathologists/American Society of Clinical Oncology (CAP/ASCO) guideline recommendations for human epidermal growth factor receptor 2 (HER2) fluorescent in situ hybridization (FISH) testing increase HER2 positive and HER2 equivocal breast cancer cases; retrospective study of HER2 FISH results of 836 invasive breast cancers. Breast Cancer Res Treat 157:405–411.  https://doi.org/10.1007/s10549-016-3824-x CrossRefGoogle Scholar
  33. 33.
    Vanden Bempt I, Van Loo P, Drijkoningen M, Neven P, Smeets A, Christiaens MR, Paridaens R, De Wolf-Peeters C (2008) Polysomy 17 in breast cancer: clinicopathologic significance and impact on HER-2 testing. J Clin Oncol 26:4869–4874.  https://doi.org/10.1200/JCO.2007.13.4296 CrossRefGoogle Scholar
  34. 34.
    Persons DL, Tubbs RR, Cooley LD, Dewald GW, Dowling PK, Du E, Mascarello JT, Rao KW, Wilson KS, Wolff DJ, Habegger-Vance G (2006) HER-2 fluorescence in situ hybridization: results from the survey program of the College of American Pathologists. Arch Pathol Lab Med 130:325–331.  https://doi.org/10.1043/1543-2165(2006)130%5B325:HFISHR%5D2.0.CO;2 Google Scholar
  35. 35.
    Press MF, Sauter G, Buyse M, Fourmanoir H, Quinaux E, Tsao-Wei DD, Eiermann W, Robert N, Pienkowski T, Crown J, Martin M, Valero V, Mackey JR, Bee V, Ma Y, Villalobos I, Campeau A, Mirlacher M, Lindsay MA, Slamon DJ (2016) HER2 gene amplification testing by fluorescent in situ hybridization (FISH): comparison of the ASCO-College of american pathologists guidelines With FISH scores used for enrollment in breast cancer International Research Group Clinical Trials. J Clin Oncol 34:3518–3528.  https://doi.org/10.1200/JCO.2016.66.6693 CrossRefGoogle Scholar
  36. 36.
    Koudelakova V, Trojanec R, Vrbkova J, Donevska S, Bouchalova K, Kolar Z, Varanasi L, Hajduch M (2016) Frequency of chromosome 17 polysomy in relation to CEP17 copy number in a large breast cancer cohort. Genes Chromosom Cancer 55(5):409–417.  https://doi.org/10.1002/gcc.22337 CrossRefGoogle Scholar
  37. 37.
    Xu B, Shen J, Guo W, Zhao W, Zhuang Y, Wang L (2018) Impact of the 2018 ASCO/CAP HER2 guidelines update for HER2 testing by FISH in breast cancer. Pathol Res Pract.  https://doi.org/10.1016/j.prp.2018.10.035 Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Zhi-Hua Liu
    • 1
  • Kun Wang
    • 2
  • Dan-Yi Lin
    • 1
  • Jie Xu
    • 1
  • Jie Chen
    • 1
  • Xiao-Yu Long
    • 1
  • Yan Ge
    • 1
  • Xin-Lan Luo
    • 1
  • Ke-Ping Zhang
    • 1
  • Yan-Hui Liu
    • 1
  • Fang-Ping Xu
    • 1
    Email author
  1. 1.Department of Pathology and Laboratory Medicine, Guangdong General HospitalGuangdong Academy of Medical SciencesGuangzhouPeople’s Republic of China
  2. 2.Department of Breast Cancer, Cancer Center, Guangdong General HospitalGuangdong Academy of Medical SciencesGuangzhouPeople’s Republic of China

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