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

  • Epidemiology
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Breast Cancer Research and Treatment Aims and scope Submit manuscript

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.

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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.

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Authors and Affiliations

  1. Providence Cancer Center, Earle A. Chiles Research Institute, 4805 NE Glisan St., Suite 6N40, Portland, OR, 97213, USA

    David B. Page & Kateri J. Spinelli

  2. Memorial Sloan Kettering Cancer Center, 300 E 66th Street, New York, NY, 10065, USA

    Hannah Wen, Edi Brogi, Dana Dure, Dara Ross, Sujata Patil, Larry Norton & Clifford Hudis

  3. Cedars-Sinai Medical Center, 8700 Beverly Blvd, AC 1042B, Los Angeles, CA, 90048, USA

    Heather L. McArthur

Authors
  1. David B. Page
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  2. Hannah Wen
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  3. Edi Brogi
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  4. Dana Dure
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  5. Dara Ross
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  6. Kateri J. Spinelli
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  7. Sujata Patil
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  8. Larry Norton
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  9. Clifford Hudis
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  10. Heather L. McArthur
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Correspondence to David B. Page or Heather L. McArthur.

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The authors declare that they have no conflict of interest.

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David B. Page and Hannah Wen are co-first authors.

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Page, D.B., Wen, H., Brogi, E. et al. Monosomy 17 in potentially curable HER2-amplified breast cancer: prognostic and predictive impact. Breast Cancer Res Treat 167, 547–554 (2018). https://doi.org/10.1007/s10549-017-4520-1

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  • DOI: https://doi.org/10.1007/s10549-017-4520-1

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