Divisional role of quantitative HER2 testing in breast cancer
Purchase on Springer.com
$39.95 / €34.95 / £29.95*
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.
Human epidermal growth factor receptor 2 (HER2) is amplified in human breast cancers in which therapy targeted to HER2 significantly improves patient outcome. We re-visited the use of real-time quantitative polymerase chain reaction (qPCR)-based assays using formalin-fixed paraffin-embedded (FFPE) tissues as alternative methods and investigated their particular clinical relevance.
DNA and RNA were isolated from FFPE specimens and HER2 status was assessed by qPCR in 249 consecutive patients with primary breast cancer. Concordance with results forg immunohistochemistry (IHC) and in situ hybridization (ISH), clinical characteristics and survival was assessed.
HER2 gene copy number had a stronger correlation with clinicopathological characteristics and excellent concordance with IHC/ISH results (Sensitivity: 96.7 %; concordance: 99.2 %). HER2 gene expression showed inadequate sensitivity, rendering it unsuitable to determine HER2 status (Sensitivity: 46.7 %; concordance: 92.1 %), but lower HER2 gene expression, leading to the classification of many cases as “false negative”, contributed to a prediction of better prognosis within the HER2-amplified subpopulation.
Quantitative HER2 assessments are suggested to have evolved their accuracy in this decade, which can be a potential alternative for HER2 diagnosis in line with the in situ method, while HER2 gene expression levels could provide additional information regarding prognosis or therapeutic strategy within a HER2-amplified subpopulation.
- Slamon D, Eiermann W, Robert N, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011;365(14):1273–83. CrossRef
- Smith I, Procter M, Gelber RD, et al. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet. 2007;369(9555):29–36. CrossRef
- Goldhirsch A, Wood WC, Coates AS, et al. Strategies for subtypes–dealing with the diversity of breast cancer: highlights of the St Gallen International expert consensus on the primary therapy of early breast cancer 2011. Ann Oncol. 2011;22(8):1736–47. CrossRef
- Kato N, Itoh H, Serizawa A, et al. Evaluation of HER2 gene amplification in invasive breast cancer using a dual-color chromogenic in situ hybridization (dual CISH). Pathol Int. 2010;60(7):510–5. CrossRef
- Middleton LP, Price KM, Puig P, et al. Implementation of American Society of Clinical Oncology/College of American Pathologists HER2 Guideline Recommendations in a tertiary care facility increases HER2 immunohistochemistry and fluorescence in situ hybridization concordance and decreases the number of inconclusive cases. Arch Pathol Lab Med. 2009;133(5):775–80.
- Hammond ME, Hayes DF, Dowsett M, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. Arch Pathol Lab Med. 2010;134(6):907–22.
- Kulka J, Tokes AM, Kaposi-Novak P, et al. Detection of HER-2/neu gene amplification in breast carcinomas using quantitative real-time PCR—a comparison with immunohistochemical and FISH results. Pathol Oncol Res. 2006;12(4):197–204. CrossRef
- Bofin AM, Ytterhus B, Martin C, et al. Detection and quantitation of HER-2 gene amplification and protein expression in breast carcinoma. Am J Clin Pathol. 2004;122(1):110–9. CrossRef
- Gjerdrum LM, Abrahamsen HN, Villegas B, et al. The influence of immunohistochemistry on mRNA recovery from microdissected frozen and formalin-fixed, paraffin-embedded sections. Diagn Mol Pathol. 2004;13(4):224–33. CrossRef
- Ntoulia M, Kaklamanis L, Valavanis C, et al. HER-2 DNA quantification of paraffin-embedded breast carcinomas with LightCycler real-time PCR in comparison to immunohistochemistry and chromogenic in situ hybridization. Clin Biochem. 2006;39(9):942–6. CrossRef
- Nistor A, Watson PH, Pettigrew N, et al. Real-time PCR complements immunohistochemistry in the determination of HER-2/neu status in breast cancer. BMC Clin Pathol. 2006;6:2. CrossRef
- Susini T, Bussani C, Marini G, et al. Preoperative assessment of HER-2/neu status in breast carcinoma: the role of quantitative real-time PCR on core-biopsy specimens. Gynecol Oncol. 2010;116(2):234–9. CrossRef
- Baehner FL, Achacoso N, Maddala T, et al. Human epidermal growth factor receptor 2 assessment in a case-control study: comparison of fluorescence in situ hybridization and quantitative reverse transcription polymerase chain reaction performed by central laboratories. J Clin Oncol. 2010;28(28):4300–6. CrossRef
- Dabbs DJ, Klein ME, Mohsin SK, et al. High false-negative rate of HER2 quantitative reverse transcription polymerase chain reaction of the Oncotype DX test: an independent quality assurance study. J Clin Oncol. 2011;29(32):4279–85. CrossRef
- Ibusuki M, Fu P, Yamamoto S et al. Establishment of a standardized gene-expression analysis system using formalin-fixed, paraffin-embedded, breast cancer specimens. Breast Cancer. 2013;20(2):159–66
- McShane LM, Altman DG, Sauerbrei W, et al. REporting recommendations for tumor MARKer prognostic studies (REMARK). Nat Clin Pract Urol. 2005;2(8):416–22. CrossRef
- Iwase H, Yamamoto Y, Kawasoe T, Ibusuki M. Advantage of sentinel lymph node biopsy before neoadjuvant chemotherapy in breast cancer treatment. Surg Today. 2009;39(5):374–80. CrossRef
- Goldhirsch A, Glick JH, Gelber RD, et al. Meeting highlights: International Consensus Panel on the treatment of primary breast cancer. Seventh International Conference on adjuvant therapy of primary breast cancer. J Clin Oncol. 2001;19(18):3817–27.
- Goldhirsch A, Wood WC, Gelber RD, et al. Meeting highlights: updated international expert consensus on the primary therapy of early breast cancer. J Clin Oncol. 2003;21(17):3357–65. CrossRef
- Goldhirsch A, Glick JH, Gelber RD, et al. Meeting highlights: International expert consensus on the primary therapy of early breast cancer 2005. Ann Oncol. 2005;16(10):1569–83. CrossRef
- Goldhirsch A, Wood WC, Gelber RD, et al. Progress and promise: highlights of the international expert consensus on the primary therapy of early breast cancer 2007. Ann Oncol. 2007;18(7):1133–44. CrossRef
- Slamon DJ, Clark GM, Wong SG, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235(4785):177–82. CrossRef
- Rhodes A, Sarson J, Assam EE, et al. The reliability of rabbit monoclonal antibodies in the immunohistochemical assessment of estrogen receptors, progesterone receptors, and HER2 in human breast carcinomas. Am J Clin Pathol. 2010;134(4):621–32. CrossRef
- Tse CH, Hwang HC, Goldstein LC, et al. Determining true HER2 gene status in breast cancers with polysomy by using alternative chromosome 17 reference genes: implications for anti-HER2 targeted therapy. J Clin Oncol. 2011;29(31):4168–74. CrossRef
- Lehmann-Che J, Amira-Bouhidel F, Turpin E, et al. Immunohistochemical and molecular analyses of HER2 status in breast cancers are highly concordant and complementary approaches. Br J Cancer. 2011;104(11):1739–46. CrossRef
- Bergqvist J, Ohd JF, Smeds J, et al. Quantitative real-time PCR analysis and microarray-based RNA expression of HER2 in relation to outcome. Ann Oncol. 2007;18(5):845–50. CrossRef
- Dowsett M, Procter M, McCaskill-Stevens W, et al. Disease-free survival according to degree of HER2 amplification for patients treated with adjuvant chemotherapy with or without 1 year of trastuzumab: the HERA Trial. J Clin Oncol. 2009;27(18):2962–9. CrossRef
- Joensuu H, Sperinde J, Leinonen M, et al. Very high quantitative tumor HER2 content and outcome in early breast cancer. Ann Oncol. 2011;22(9):2007–13. CrossRef
- Allouche A, Nolens G, Tancredi A, et al. The combined immunodetection of AP-2alpha and YY1 transcription factors is associated with ERBB2 gene overexpression in primary breast tumors. Breast Cancer Res. 2008;10(1):R9. CrossRef
- Epis MR, Giles KM, Barker A, et al. miR-331-3p regulates ERBB-2 expression and androgen receptor signaling in prostate cancer. J Biol Chem. 2009;284(37):24696–704. CrossRef
- Jan CI, Yu CC, Hung MC, et al. Tid1, CHIP and ErbB2 interactions and their prognostic implications for breast cancer patients. J Pathol. 2011;225(3):424–37. CrossRef
- Roepstorff K, Grovdal L, Grandal M, et al. Endocytic downregulation of ErbB receptors: mechanisms and relevance in cancer. Histochem Cell Biol. 2008;129(5):563–78. CrossRef
- Divisional role of quantitative HER2 testing in breast cancer
- Print ISSN
- Online ISSN
- Springer Japan
- Additional Links
- Breast cancer
- Human epidermal growth factor 2
- Real-time quantitative PCR
- Gene copy number
- Gene expression analysis
- Industry Sectors
- Author Affiliations
- 1. The Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo Kumamoto, Kumamoto, 860-8556, Japan
- 2. Department of General Surgery First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, People’s Republic of China
- 3. Department of Surgical Pathology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo Kumamoto, Kumamoto, 860-8556, Japan