Breast Cancer Research and Treatment

, Volume 167, Issue 2, pp 547–554 | Cite as

Monosomy 17 in potentially curable HER2-amplified breast cancer: prognostic and predictive impact

  • David B. Page
  • Hannah Wen
  • Edi Brogi
  • Dana Dure
  • Dara Ross
  • Kateri J. Spinelli
  • Sujata Patil
  • Larry Norton
  • Clifford Hudis
  • Heather L. McArthur



HER2 copy number by fluorescence in situ hybridization (FISH) is typically reported relative to the centromere enumeration probe 17 (CEP17). HER2/CEP17 ratio could be impacted by alterations in the number of chromosome 17 copies. Monosomy of chromosome 17 (m17) is found in ~ 1900 cases of early-stage HER2-positive breast cancer annually in the United States; however, the efficacy of HER2-directed trastuzumab therapy in these patients is not well characterized. Here, we retrospectively identified HER2-amplified, stage I–III breast cancers with m17 and characterized the impact of trastuzumab treatment.


From January 1, 2000 to June 1, 2011, we identified 99 women with HER2-amplified m17 breast cancers, as defined by a CEP17 signal of < 1.5 per nucleus and a HER2/CEP17 ratio of ≥ 2.0.


Most HER2-amplified m17 patients were treated with trastuzumab plus chemotherapy (51%, n = 50), whereas 31% (n = 31) received chemotherapy alone and 18% (n = 18) received no chemotherapy. The 4-year overall survival (OS) was superior with trastuzumab compared to chemotherapy alone or no chemotherapy (100 vs. 93 vs. 81%, respectively; p = 0.005). OS was not influenced by estrogen/progesterone-receptor (ER/PR) status, tumor stage, or degree of FISH positivity. A proportion of patients who would be considered HER2-negative by standard immunohistochemistry staging criteria (0–1+) were HER2 amplified by FISH.


In the largest series reported to date, patients with HER2-amplified m17 cancers treated with trastuzumab have outcomes comparable to patients from the large phase III adjuvant trastuzumab trials who were HER2-positive, supporting the critical role of HER2-directed therapy in this patient population.


Monosomy 17 Aneusomy 17 HER2 Trastuzumab CEP17 Polysomy 17 HER2-amplified FISH Chromosome 17 



This study was supported in part by a National Institute of Health/National Cancer Institute P30CA008748 Institutional grant awarded to Memorial Sloan Kettering Cancer Center.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Bartlett JM, Going JJ, Mallon EA et al (2001) Evaluating HER2 amplification and overexpression in breast cancer. J Pathol 195:422–428CrossRefPubMedGoogle Scholar
  2. 2.
    Bartlett J, Mallon E, Cooke T (2003) The clinical evaluation of HER-2 status: which test to use? J Pathol 199:411–417CrossRefPubMedGoogle Scholar
  3. 3.
    Hudis CA (2007) Trastuzumab–mechanism of action and use in clinical practice. N Engl J Med 357:39–51CrossRefPubMedGoogle Scholar
  4. 4.
    Slamon D, Eiermann W, Robert N et al (2011) Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 365:1273–1283CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Perez EA, Reinholz MM, Hillman DW et al (2010) HER2 and chromosome 17 effect on patient outcome in the N9831 adjuvant trastuzumab trial. J Clin Oncol 28:4307–4315CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Siegel R, Naishadham D, Jemal A (2013) Cancer statistics, 2013. CA Cancer J Clin 63:11–30CrossRefPubMedGoogle Scholar
  7. 7.
    Risio M, Casorzo L, Redana S, Montemurro F (2005) HER2 gene-amplified breast cancers with monosomy of chromosome 17 are poorly responsive to trastuzumab-based treatment. Oncol Rep 13:305–309PubMedGoogle Scholar
  8. 8.
    Bieche I, Tomasetto C, Regnier CH, Moog-Lutz C, Rio MC, Lidereau R (1996) Two distinct amplified regions at 17q11-q21 involved in human primary breast cancer. Can Res 56:3886–3890Google Scholar
  9. 9.
    Engstrom MJ, Ytterhus B, Vatten LJ, Opdahl S, Bofin AM (2014) TOP2A gene copy number change in breast cancer. J Clin Pathol 67:420–425CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Press MF, Sauter G, Buyse M et al (2011) Alteration of topoisomerase II-alpha gene in human breast cancer: association with responsiveness to anthracycline-based chemotherapy. J Clin Oncol 29:859–867CrossRefPubMedGoogle Scholar
  11. 11.
    Reinholz MM, Bruzek AK, Visscher DW et al (2009) Breast cancer and aneusomy 17: implications for carcinogenesis and therapeutic response. Lancet Oncol 10:267–277CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Ma Y, Lespagnard L, Durbecq V et al (2005) Polysomy 17 in HER-2/neu status elaboration in breast cancer: effect on daily practice. Clin Cancer Res 11:4393–4399CrossRefPubMedGoogle Scholar
  13. 13.
    Perez EA, Suman VJ, Davidson NE et al (2006) HER2 testing by local, central, and reference laboratories in specimens from the North Central Cancer Treatment Group N9831 intergroup adjuvant trial. J Clin Oncol 24:3032–3038CrossRefPubMedGoogle Scholar
  14. 14.
    Wolff AC, Hammond ME, 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 31:3997–4013CrossRefPubMedGoogle Scholar
  15. 15.
    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 138:99–108CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Hudis CA, Barlow WE, Costantino JP et al (2007) Proposal for standardized definitions for efficacy end points in adjuvant breast cancer trials: the STEEP system. J Clin Oncol 25:2127–2132CrossRefPubMedGoogle Scholar
  17. 17.
    NCCN Clinical Practice Guidelines in Oncology (2015) Breast Cancer, Version 3.2015. Accessed 24 July 2015
  18. 18.
    Greenlee RT, Goodman MT, Lynch CF, Platz CE, Havener LA, Howe HL (2010) The occurrence of rare cancers in U.S. adults, 1995–2004. Public Health Rep 125:28–43CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Verma S, Miles D, Gianni L et al (2012) Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 367:1783–1791CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Hurvitz SA, Dirix L, Kocsis J et al (2013) Phase II randomized study of trastuzumab emtansine versus trastuzumab plus docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol 31:1157–1163CrossRefPubMedGoogle Scholar
  21. 21.
    Frontline T-DM1 Results Disappointing in Phase III MARIANNE Trial (2014) Accessed 27 July 27 2015
  22. 22.
    Trial identifier NCT01853748 Accessed 27 July 2015
  23. 23.
    Mertens F, Johansson B, Mitelman F (1994) Isochromosomes in neoplasia. Genes Chromosom Cancer 10:221–230CrossRefPubMedGoogle Scholar
  24. 24.
    Pandrangi SL, Raju Bagadi SA, Sinha NK et al (2014) Establishment and characterization of two primary breast cancer cell lines from young Indian breast cancer patients: mutation analysis. Cancer Cell Int 14:14CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Tse CH, Hwang HC, Goldstein LC et al (2011) 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 29:4168–4174CrossRefPubMedGoogle Scholar
  26. 26.
    Watters AD, Going JJ, Cooke TG et al (2003) Chromosome 17 aneusomy is associated with poor prognostic factors in invasive breast carcinoma. Breast Cancer Res Treat 77:109–114CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • David B. Page
    • 1
  • Hannah Wen
    • 2
  • Edi Brogi
    • 2
  • Dana Dure
    • 2
  • Dara Ross
    • 2
  • Kateri J. Spinelli
    • 1
  • Sujata Patil
    • 2
  • Larry Norton
    • 2
  • Clifford Hudis
    • 2
  • Heather L. McArthur
    • 3
  1. 1.Providence Cancer CenterEarle A. Chiles Research InstitutePortlandUSA
  2. 2.Memorial Sloan Kettering Cancer CenterNew YorkUSA
  3. 3.Cedars-Sinai Medical CenterLos AngelesUSA

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