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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
Epidemiology

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

Keywords

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

Notes

Acknowledgements

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.

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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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