Skip to main content
SpringerLink
Log in
Book cover

Encyclopedia of Pathology pp 1–11Cite as

HER2 in Breast Cancer

  • Living reference work entry
  • First Online:

Part of the book series: Encyclopedia of Pathology ((EP))

Synonyms

ERBB2

Definition

HER2, whose official name is “erb-b2 receptor tyrosine kinase 2,” is a tyrosine kinase receptor belonging to the human epidermal growth factor receptor family. It represents the second member of this family (and therefore called HER2), and it is an orphan receptor, meaning that no specific ligands are known for this receptor.

Features

About 15% of all invasive breast carcinomas present HER2 overexpression and/or HER2 gene amplification, thus identifying a subset of breast carcinomas that can be treated in a targeted fashion. It has been shown that HER2-positive breast carcinomas are often poorly differentiated and of no special types (NST) (Invasive Carcinoma NST).

Ductal carcinoma in situ (DCIS) of high nuclear grade with comedonecrosis (Ductal Carcinoma In Situ) is frequently HER2-positive and may be associated with an invasive carcinoma. However, HER2 overexpression in DCIS is not considered for anti-HER2 therapy. Cells of Paget disease of the nipple (Paget...

This is a preview of subscription content, log in via an institution.

References and Further Reading

  • Arriola, E., Marchio, C., Tan, D. S., Drury, S. C., Lambros, M. B., Natrajan, R., Rodriguez-Pinilla, S. M., Mackay, A., Tamber, N., Fenwick, K., Jones, C., Dowsett, M., Ashworth, A., & Reis-Filho, J. S. (2008). Genomic analysis of the HER2/TOP2A amplicon in breast cancer and breast cancer cell lines. Laboratory Investigation, 88, 491–503.

    Article  CAS  Google Scholar 

  • Ballard, M., Jalikis, F., Krings, G., Schmidt, R. A., Chen, Y. Y., Rendi, M. H., Dintzis, S. M., Jensen, K. C., West, R. B., Sibley, R. K., Troxell, M. L., & Allison, K. H. (2017). ‘Non-classical’ HER2 FISH results in breast cancer: A multi-institutional study. Modern Pathology, 30, 227–235.

    Article  CAS  Google Scholar 

  • Bose, R., Kavuri, S. M., Searleman, A. C., Shen, W., Shen, D., Koboldt, D. C., Monsey, J., Goel, N., Aronson, A. B., Li, S., Ma, C. X., Ding, L., Mardis, E. R., & Ellis, M. J. (2013). Activating HER2 mutations in HER2 gene amplification negative breast cancer. Cancer Discovery, 3, 224–237.

    Article  CAS  Google Scholar 

  • Ciriello, G., Gatza, M. L., Beck, A. H., Wilkerson, M. D., Rhie, S. K., Pastore, A., Zhang, H., McLellan, M., Yau, C., Kandoth, C., Bowlby, R., Shen, H., Hayat, S., Fieldhouse, R., Lester, S. C., Tse, G. M., Factor, R. E., Collins, L. C., Allison, K. H., Chen, Y. Y., Jensen, K., Johnson, N. B., Oesterreich, S., Mills, G. B., Cherniack, A. D., Robertson, G., Benz, C., Sander, C., Laird, P. W., Hoadley, K. A., King, T. A., Network, T. R., & Perou, C. M. (2015). Comprehensive molecular portraits of invasive lobular breast cancer. Cell, 163, 506–519.

    Article  CAS  Google Scholar 

  • Cocco, E., Javier Carmona, F., Razavi, P., Won, H. H., Cai, Y., Rossi, V., Chan, C., Cownie, J., Soong, J., Toska, E., Shifman, S. G., Sarotto, I., Savas, P., Wick, M. J., Papadopoulos, K. P., Moriarty, A., Cutler, R. E., Jr., Avogadri-Connors, F., Lalani, A. S., Bryce, R. P., Chandarlapaty, S., Hyman, D. M., Solit, D. B., Boni, V., Loi, S., Baselga, J., Berger, M. F., Montemurro, F., & Scaltriti, M. (2018). Neratinib is effective in breast tumors bearing both amplification and mutation of ERBB2 (HER2). Science Signaling, 11, pii: eaat9773.

    Article  Google Scholar 

  • Curtis, C., Shah, S. P., Chin, S. F., Turashvili, G., Rueda, O. M., Dunning, M. J., Speed, D., Lynch, A. G., Samarajiwa, S., Yuan, Y., Graf, S., Ha, G., Haffari, G., Bashashati, A., Russell, R., McKinney, S., METABRIC Group, Langerod, A., Green, A., Provenzano, E., Wishart, G., Pinder, S., Watson, P., Markowetz, F., Murphy, L., Ellis, I., Purushotham, A., Borresen-Dale, A. L., Brenton, J. D., Tavare, S., Caldas, C., & Aparicio, S. (2012). The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature, 486, 346–352.

    Article  CAS  Google Scholar 

  • Ercolani, C., Marchio, C., Di Benedetto, A., Fabi, A., Perracchio, L., Vici, P., Sperati, F., Buglioni, S., Arena, V., Pescarmona, E., Sapino, A., Terrenato, I., & Mottolese, M. (2017). Breast carcinomas with low amplified/equivocal HER2 by Ish: Potential supporting role of multiplex ligation-dependent probe amplification. Journal of Experimental & Clinical Cancer Research, 36, 143.

    Article  Google Scholar 

  • Fang, Y., Jiang, Y., Wang, X., Yang, X., Gao, Y., & Wang, J. (2014). Somatic mutations of the HER2 in metastatic breast cancer. Tumour Biology, 35, 11851–11854.

    Article  CAS  Google Scholar 

  • Fehrenbacher, L., Cecchini, R., Geyer, C., Rastogi, P., Costantino, J., Atkins, J., Polikoff, J., Boileau, J.-F., Provencher, L., Stokoe, C., Moore, T., Robidoux, A., Borges, V., Albain, K., Swain, S., Paik, S., Mamounas, E., & Wolmark, N. (2018). Abstract GS1-02: NSABP B-47 (NRG oncology): Phase III randomized trial comparing adjuvant chemotherapy with adriamycin (A) and cyclophosphamide (C) → weekly paclitaxel (WP), or docetaxel (T) and C with or without a year of trastuzumab (H) in women with node-positive or high-risk node-negative invasive breast cancer (IBC) expressing HER2 staining intensity of IHC 1+ or 2+ with negative FISH (HER2-Low IBC). Cancer Research, 78(4 Supplement), GS1-02-GS01-02.

    Article  Google Scholar 

  • Hyman, D. M., Piha-Paul, S. A., Won, H., Rodon, J., Saura, C., Shapiro, G. I., Juric, D., Quinn, D. I., Moreno, V., Doger, B., Mayer, I. A., Boni, V., Calvo, E., Loi, S., Lockhart, A. C., Erinjeri, J. P., Scaltriti, M., Ulaner, G. A., Patel, J., Tang, J., Beer, H., Selcuklu, S. D., Hanrahan, A. J., Bouvier, N., Melcer, M., Murali, R., Schram, A. M., Smyth, L. M., Jhaveri, K., Li, B. T., Drilon, A., Harding, J. J., Iyer, G., Taylor, B. S., Berger, M. F., Cutler, R. E., Jr., Xu, F., Butturini, A., Eli, L. D., Mann, G., Farrell, C., Lalani, A. S., Bryce, R. P., Arteaga, C. L., Meric-Bernstam, F., Baselga, J., & Solit, D. B. (2018). HER kinase inhibition in patients with HER2- and HER3-mutant cancers. Nature, 554, 189–194.

    Article  CAS  Google Scholar 

  • Isola, J., Tanner, M., Forsyth, A., Cooke, T. G., Watters, A. D., & Bartlett, J. M. (2004). Interlaboratory comparison of HER-2 oncogene amplification as detected by chromogenic and fluorescence in situ hybridization. Clinical Cancer Research, 10, 4793–4798.

    Article  CAS  Google Scholar 

  • Kancha, R. K., von Bubnoff, N., Bartosch, N., Peschel, C., Engh, R. A., & Duyster, J. (2011). Differential sensitivity of ERBB2 kinase domain mutations towards lapatinib. PLoS One, 6, e26760.

    Article  CAS  Google Scholar 

  • Lee, J. W., Soung, Y. H., Seo, S. H., Kim, S. Y., Park, C. H., Wang, Y. P., Park, K., Nam, S. W., Park, W. S., Kim, S. H., Lee, J. Y., Yoo, N. J., & Lee, S. H. (2006). Somatic mutations of ERBB2 kinase domain in gastric, colorectal, and breast carcinomas. Clinical Cancer Research, 12, 57–61.

    Article  CAS  Google Scholar 

  • Lien, H. C., Chen, Y. L., Juang, Y. L., & Jeng, Y. M. (2015). Frequent alterations of HER2 through mutation, amplification, or overexpression in pleomorphic lobular carcinoma of the breast. Breast Cancer Research and Treatment, 150, 447–455.

    Article  CAS  Google Scholar 

  • Ma, C. X., Bose, R., Gao, F., Freedman, R. A., Telli, M. L., Kimmick, G., Winer, E., Naughton, M., Goetz, M. P., Russell, C., Tripathy, D., Cobleigh, M., Forero, A., Pluard, T. J., Anders, C., Niravath, P. A., Thomas, S., Anderson, J., Bumb, C., Banks, K. C., Lanman, R. B., Bryce, R., Lalani, A. S., Pfeifer, J., Hayes, D. F., Pegram, M., Blackwell, K., Bedard, P. L., Al-Kateb, H., & Ellis, M. J. C. (2017). Neratinib efficacy and circulating tumor DNA detection of HER2 mutations in HER2 nonamplified metastatic breast cancer. Clinical Cancer Research, 23, 5687–5695.

    Article  CAS  Google Scholar 

  • Marchio, C., Lambros, M. B., Gugliotta, P., Di Cantogno, L. V., Botta, C., Pasini, B., Tan, D. S., Mackay, A., Fenwick, K., Tamber, N., Bussolati, G., Ashworth, A., Reis-Filho, J. S., & Sapino, A. (2009). Does chromosome 17 centromere copy number predict polysomy in breast cancer? A fluorescence in situ hybridization and microarray-based CGH analysis. Journal of Pathology, 219, 16–24.

    Article  CAS  Google Scholar 

  • Marchio, C., Dell’Orto, P., Annaratone, L., Geyer, F. C., Venesio, T., Berrino, E., Verdun di Cantogno, L., Garofoli, A., Rangel, N., Casorzo, L., dell’Aglio, C., Gugliotta, P., Trisolini, E., Beano, A., Pietribiasi, F., Orlassino, R., Cassoni, P., Pich, A., Montemurro, F., Mottolese, M., Vincent-Salomon, A., Penault-Llorca, F., Medico, E., Ng, C. K. Y., Viale, G., & Sapino, A. (2018). The dilemma of HER2 double-equivocal breast carcinomas: Genomic profiling and implications for treatment. American Journal of Surgical Pathology, 42, 1190–1200.

    Article  Google Scholar 

  • Moelans, C. B., de Weger, R. A., & van Diest, P. J. (2010). Absence of chromosome 17 polysomy in breast cancer: Analysis by CEP17 chromogenic in situ hybridization and multiplex ligation-dependent probe amplification. Breast Cancer Research and Treatment, 120, 1–7.

    Article  CAS  Google Scholar 

  • Park, Y. H., Shin, H. T., Jung, H. H., Choi, Y. L., Ahn, T., Park, K., Lee, A., Do, I. G., Kim, J. Y., Ahn, J. S., Park, W. Y., & Im, Y. H. (2015). Role of HER2 mutations in refractory metastatic breast cancers: Targeted sequencing results in patients with refractory breast cancer. Oncotarget, 6, 32027–32038.

    PubMed  PubMed Central  Google Scholar 

  • Petrelli, F., Tomasello, G., Barni, S., Lonati, V., Passalacqua, R., & Ghidini, M. (2017). Clinical and pathological characterization of HER2 mutations in human breast cancer: A systematic review of the literature. Breast Cancer Research and Treatment, 166, 339–349.

    Article  CAS  Google Scholar 

  • Press, M. F., Sauter, G., Buyse, M., Fourmanoir, H., Quinaux, E., Tsao-Wei, D. D., Eiermann, W., Robert, N., Pienkowski, T., Crown, J., Martin, M., Valero, V., Mackey, J. R., Bee, V., Ma, Y., Villalobos, I., Campeau, A., Mirlacher, M., Lindsay, M. A., & Slamon, D. J. (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. Journal of Clinical Oncology, 34, 3518–3528.

    Article  CAS  Google Scholar 

  • Ragazzi, M., Bisagni, A., Gasparini, E., Kuhn, E., Bassano, C., Tamagnini, I., Foroni, M., Bortesi, M., Falco, G., Ferrari, G., Braglia, L., Savoldi, L., Bologna, A., Di Cicilia, R., Bisagni, G., & Gardini, G. (2017). Impact of 2013 ASCO/CAP guidelines on HER2 determination of invasive breast cancer: A single institution experience using frontline dual-color FISH. Breast, 34, 65–72.

    Article  CAS  Google Scholar 

  • Rondon-Lagos, M., Verdun Di Cantogno, L., Rangel, N., Mele, T., Ramirez-Clavijo, S. R., Scagliotti, G., Marchio, C., & Sapino, A. (2014). Unraveling the chromosome 17 patterns of FISH in interphase nuclei: An in-depth analysis of the HER2 amplicon and chromosome 17 centromere by karyotyping, FISH and M-FISH in breast cancer cells. BMC Cancer, 14, 922.

    Article  Google Scholar 

  • Ross, J. S., Wang, K., Sheehan, C. E., Boguniewicz, A. B., Otto, G., Downing, S. R., Sun, J., He, J., Curran, J. A., Ali, S., Yelensky, R., Lipson, D., Palmer, G., Miller, V. A., & Stephens, P. J. (2013). Relapsed classic E-cadherin (CDH1)-mutated invasive lobular breast cancer shows a high frequency of HER2 (ERBB2) gene mutations. Clinical Cancer Research, 19, 2668–2676.

    Article  CAS  Google Scholar 

  • Sapino, A., Maletta, F., Verdun di Cantogno, L., Macri, L., Botta, C., Gugliotta, P., Scalzo, M. S., Annaratone, L., Balmativola, D., Pietribiasi, F., Bernardi, P., Arisio, R., Viberti, L., Guzzetti, S., Orlassino, R., Ercolani, C., Mottolese, M., Viale, G., & Marchio, C. (2014). Gene status in HER2 equivocal breast carcinomas: Impact of distinct recommendations and contribution of a polymerase chain reaction-based method. The Oncologist, 19, 1118–1126.

    Article  CAS  Google Scholar 

  • Valent, A., Penault-Llorca, F., Cayre, A., & Kroemer, G. (2013). Change in HER2 (ERBB2) gene status after taxane-based chemotherapy for breast cancer: Polyploidization can lead to diagnostic pitfalls with potential impact for clinical management. Cancer Genetics, 206, 37–41.

    Article  CAS  Google Scholar 

  • Wolff, A. C., Hammond, M. E., Hicks, D. G., Dowsett, M., McShane, L. M., Allison, K. H., Allred, D. C., Bartlett, J. M., Bilous, M., Fitzgibbons, P., Hanna, W., Jenkins, R. B., Mangu, P. B., Paik, S., Perez, E. A., Press, M. F., Spears, P. A., Vance, G. H., Viale, G., Hayes, D. F., 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. Journal of Clinical Oncology, 31, 3997–4013.

    Article  Google Scholar 

  • Wolff, A. C., Hammond, M. E. H., Allison, K. H., Harvey, B. E., Mangu, P. B., Bartlett, J. M. S., Bilous, M., Ellis, I. O., Fitzgibbons, P., Hanna, W., Jenkins, R. B., Press, M. F., Spears, P. A., Vance, G. H., Viale, G., McShane, L. M., & 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. Journal of Clinical Oncology, 36, 2105–2122.

    Article  Google Scholar 

  • Yeh, I. T., Martin, M. A., Robetorye, R. S., Bolla, A. R., McCaskill, C., Shah, R. K., Gorre, M. E., Mohammed, M. S., & Gunn, S. R. (2009). Clinical validation of an array CGH test for HER2 status in breast cancer reveals that polysomy 17 is a rare event. Modern Pathology, 22, 1169–1175.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Sciences, University of Turin, Turin, Italy

    Laura Annaratone & Caterina Marchiò

  2. Pathology Division, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy

    Ivana Sarotto & Caterina Marchiò

Authors
  1. Laura Annaratone
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ivana Sarotto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Caterina Marchiò
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Caterina Marchiò .

Editor information

Editors and Affiliations

  1. NIJMEGEN, The Netherlands

    J.H.J.M. van Krieken

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Annaratone, L., Sarotto, I., Marchiò, C. (2019). HER2 in Breast Cancer. In: van Krieken, J. (eds) Encyclopedia of Pathology. Encyclopedia of Pathology. Springer, Cham. https://doi.org/10.1007/978-3-319-28845-1_4710-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-28845-1_4710-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-28845-1

  • Online ISBN: 978-3-319-28845-1

  • eBook Packages: Springer Reference MedicineReference Module Medicine

Publish with us

Policies and ethics

Search

Navigation