Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 3/2017

01-12-2017 | Preclinical study

Impact of repeat HER2 testing after initial equivocal HER2 FISH results using 2013 ASCO/CAP guidelines

Authors: Fang-Ping Xu, Kun Wang, Jie Xu, Jie Chen, Yi-Fang Zhang, Hong-Mei Wu, Ming-Hui Zhang, Xiao-Xu Long, Xin-Lan Luo, Ke-Ping Zhang, Dan-Yi Lin, Yan-Hui Liu

Published in: Breast Cancer Research and Treatment | Issue 3/2017

Login to get access

Abstract

Purpose

The updated 2013 American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing have made some major changes in HER2 fluorescence in situ hybridization (FISH) interpretation criteria with additional FISH equivocal cases. Repeat HER2 testing is recommended after initial HER2 FISH equivocal results; however, little is known about its impact on final HER2 status. The aim of this study is to investigate whether reflex test clarifies HER2 status, and to characterize clinicopathological features of the newly defined HER2 equivocal group.

Methods

A total of 886 consecutive cases of primary invasive breast cancer conducted with dual-probe HER2 FISH testing between November 2013 and December 2015 were reviewed. HER2 immunohistochemistry (IHC) and FISH testing were performed on a different tissue block or a new specimen after initial HER2 FISH equivocal results.

Results

Compared to 2007 guideline, 85 (9.6%) cases changed their category by using 2013 guideline. The major change of the 85 cases is that 57 (6.4%) cases in HER2 FISH-negative category changed to equivocal, and the equivocal category cases increased from 36 to 67. HER2 FISH equivocal was significantly associated with HER2 IHC equivocal (2+) and chromosome 17 polysomy (P < 0.01). Repeat testing by IHC and FISH clarified HER2 status in 33 and 42% of HER2 equivocal cases, respectively. Overall 32 (48%) initial HER2 equivocal cases stayed HER2 equivocal after repeat FISH and or IHC testing. These tumors were ER/PR+, with high KI-67 index.

Conclusion

New guidelines classify more HER2 FISH equivocal cases. Repeat HER2 testing clarifies HER2 status in about 50% of initial HER2 FISH equivocal cases. In addition, HER2 equivocal cases merit further study as there is limited information about prognosis and optimal treatment strategy for this population.
Literature
1.
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(4785):177–182CrossRefPubMed
2.
Burstein HJ (2005) The distinctive nature of HER-2-positive breast cancer. N Engl J Med 353:1652–1654CrossRefPubMed
3.
Perez EA, Romond EH, Suman VJ, Jeong JH, Davidson NE, Geyer CE Jr, Martino S, Mamounas EP, Kaufman PA, Wolmark N (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 29:3366–3373CrossRefPubMedPubMedCentral
4.
Gianni L, Dafni U, Gelber RD, Azambuja E, Muehlbauer S, Goldhirsch A, Untch M, Smith I, Baselga J, Jackisch C, Cameron D, Mano M, Pedrini JL, Veronesi A, Mendiola C, Pluzanska A, Semiglazov V, Vrdoljak E, Eckart MJ, Shen Z, Skiadopoulos G, Procter M, Pritchard KI, Piccart-Gebhart MJ, Bell R, Herceptin Adjuvant (HERA) Trial Study Team (2011) Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial. Lancet Oncol 12(3):236–244CrossRefPubMed
5.
Yaziji H, Goldstein LC, Barry TS, Werling R, Hwang H, Ellis GK, Gralow JR, Livingston RB, Gown AM (2004) HER-2 testing in breast cancer using parallel tissue-based methods. JAMA 291(16):1972–1977CrossRefPubMed
6.
Sapino A, Goia M, Recupero D, Marchio` C (2013) Current challenges for HER2 testing in diagnostic pathology: state of the art and controversial issues. Front Oncol 3:129CrossRefPubMedPubMedCentral
7.
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(4):207–210CrossRefPubMed
8.
Lidgren M, Wilking N, Jo¨nsson B, Rehnberg C (2008) Cost effectiveness of HER2 testing and trastuzumab therapy for metastatic breast cancer. Acta Oncol 47(6):1018–1028CrossRefPubMed
9.
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 Pathologists (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(1):118–145CrossRefPubMed
10.
Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, Allred DC, Bartlett JM, Bilous M, Fitzgibbons P, Hanna W, Jenkins RB, Mangu PB, Paik S, Perez EA, Press MF, Spears PA, Vance GH, Viale G, Hayes DF, American Society of Clinical Oncology; College of American Pathologists (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(31):3997–4013CrossRefPubMed
11.
Long TH, Lawce H, Durum C, Moore SR, Olson SB, Gatter K, Troxell ML (2015) The new equivocal: changes to HER2 FISH results when applying the 2013 ASCO/CAP guidelines. Am J Clin Pathol 144(2):253–262CrossRefPubMed
12.
Sapino A, Maletta F, Verdun di Cantogno L, Macrì L, Botta C, Gugliotta P, Scalzo MS, Annaratone L, Balmativola D, Pietribiasi F, Bernardi P, Arisio R, Viberti L, Guzzetti S, Orlassino R, Ercolani C, Mottolese M, Viale G, Marchiò C (2014) Gene status in HER2 equivocal breast carcinomas: impact of distinct recommendations and contribution of a polymerase chain reaction-based method. Oncologist 19(11):1118–1126CrossRefPubMedPubMedCentral
13.
Espinet B, Puiggros AM, Corominas JM, Iglesias M, Rodriguez-Rivera M, Melero MC, Albanell J, Tusquets I, Servitja S, Serrano S, Salido M (2015) Increase in equivocal in situ hybridization results in ASCO/CAP guidelines for HER2 testing in invasive breast cancer: comparison with the 2007 criteria (Abstract). Mod Pathol 28:43A
14.
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(3):405–411CrossRefPubMed
15.
Muller KE, Marotti JD, Memoli VA, Wells WA, Tafe LJ (2015) Impact of the 2013 ASCO/CAP HER2 guideline updates at an academic medical center that performs primary HER2 FISH testing: increase in equivocal results and utility of reflex immunohistochemistry. Am J Clin Pathol 144(2):247–252CrossRefPubMed
16.
Qian XL, Wen HY, Yang YL, Gu F, Guo XJ, Liu FF, Zhang L, Zhang XM, Fu L (2016) Assessment of dual-probe Her-2 fluorescent in situ hybridization in breast cancer by the 2013 ASCO/CAP guidelines produces more equivocal results than that by the 2007 ASCO/CAP guidelines. Breast Cancer Res Treat 159(1):31–39CrossRefPubMedPubMedCentral
17.
Tchrakian N, Flanagan L, Harford J, Gannon JM, Quinn CM (2016) New ASCO/CAP guideline recommendations for HER2 testing increase the proportion of reflex in situ hybridization tests and of HER2 positive breast cancers. Virchows Arch 468(2):207–211CrossRefPubMed
18.
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 Immunohistochemistry HER-2 scoring criterion in breast cancer. Am J Clin Pathol 132(1):74–79CrossRefPubMed
19.
Lim TH, Lim AS, Thike AA, Tien SL, Tan PH (2016) Implications of the Updated 2013 American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations on human epidermal growth factor receptor 2 gene testing using immunohistochemistry and fluorescence in situ hybridization for breast cancer. Arch Pathol Lab Med 140(2):140–147CrossRefPubMed
20.
Bethune GC, Veldhuijzen van Zanten D, MacIntosh RF, Rayson D, Younis T, Thompson K, Barnes PJ (2015) Impact of the 2013 American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing of invasive breast carcinoma: a focus on tumours assessed as ‘equivocal’ for HER2 gene amplification by fluorescence in situ hybridization. Histopathology 67(6):880–887CrossRefPubMed
21.
Hanna WM, Rüschoff 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(1):4–18CrossRefPubMed
22.
Stoss OC, Scheel A, Nagelmeier I, Schildhaus HU, Henkel T, Viale G, Jasani B, Untch M, Rüschoff J (2015) Impact of updated HER2 testing guidelines in breast cancer–re-evaluation of HERA trial fluorescence in situ hybridization data. Mod Pathol 28(12):1528–1534CrossRefPubMed
23.
Fan YS, Casas CE, Peng J, Watkins M, Fan L, Chapman J, Ikpatt OF, Gomez C, Zhao W, Reis IM (2016) HER2 FISH classification of equivocal HER2 IHC breast cancers with use of the 2013 ASCO/CAP practice guideline. Breast Cancer Res Treat 155(3):457–462CrossRefPubMed
24.
Ji H, Xuan Q, Nanding A, Zhang H, Zhang Q (2015) The clinicopathologic and prognostic value of altered chromosome 17 centromere copy number in HER2 fish equivocal breast carcinomas. PLoS ONE 10(7):e0132824CrossRefPubMedPubMedCentral
25.
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 Chromosomes Cancer 55(5):409–417CrossRefPubMed
26.
Shah MV, Wiktor AE, Meyer RG, Tenner KS, Ballman KV, Green SJ, Sukov WR, Ketterling RP, Perez EA, Jenkins RB (2016) Change in Pattern of HER2 Fluorescent in Situ Hybridization (FISH) results in breast cancers submitted for Fish testing: experience of a reference laboratory using US Food and Drug Administration Criteria and American Society of Clinical Oncology and College of American Pathologists Guidelines. J Clin Oncol 34:3502–3510CrossRefPubMed
27.
Striebel JM, Bhargava R, Horbinski C, Surti U, Dabbs DJ (2008) The equivocally amplified HER2 FISH result on breast core biopsy: indications for further sampling do affect patient management. Am J Clin Pathol 129(3):383–390CrossRefPubMed
28.
Jang MH, Kim EJ, Kim HJ, Chung YR, Park SY (2015) Assessment of HER2 status in invasive breast cancers with increased centromere 17 copy number. Breast Cancer Res Treat 153(1):67–77CrossRefPubMed
29.
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 34:3518–3528CrossRefPubMedPubMedCentral
30.
Perez EA, Reinholz MM, Hillman DW, Tenner KS, Schroeder MJ, Davidson NE, Martino S, Sledge GW, Harris LN, Gralow JR, Dueck AC, Ketterling RP, Ingle JN, Lingle WL, Kaufman PA, Visscher DW, Jenkins RB (2010) HER2 and chromosome 17 effect on patient outcome in the N9831 adjuvant trastuzumab trial. J Clin Oncol 28(28):4307–4315CrossRefPubMedPubMedCentral
Metadata
Title
Impact of repeat HER2 testing after initial equivocal HER2 FISH results using 2013 ASCO/CAP guidelines
Authors
Fang-Ping Xu
Kun Wang
Jie Xu
Jie Chen
Yi-Fang Zhang
Hong-Mei Wu
Ming-Hui Zhang
Xiao-Xu Long
Xin-Lan Luo
Ke-Ping Zhang
Dan-Yi Lin
Yan-Hui Liu
Publication date
01-12-2017
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2017
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-017-4479-y

Other articles of this Issue 3/2017

Breast Cancer Research and Treatment 3/2017 Go to the issue

Epidemiology

Increased risk of arterial thromboembolism in older men with breast cancer

Epidemiology

Survival and level of care among breast cancer patients with brain metastases treated with whole brain radiotherapy

Erratum

Erratum to: Utilization of bioimpedance spectroscopy in the prevention of chronic breast cancer-related lymphedema

Epidemiology

Clinical pattern of primary systemic therapy and outcomes of estrogen receptor-positive, HER2-negative metastatic breast cancer: a review of a single institution

Clinical trial

Utilization of bioimpedance spectroscopy in the prevention of chronic breast cancer-related lymphedema

Preclinical study

BRCA1-mimetic compound NSC35446.HCl inhibits IKKB expression by reducing estrogen receptor-α occupancy in the IKKB promoter and inhibits NF-κB activity in antiestrogen-resistant human breast cancer cells
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits