Monosomy 17 in potentially curable HER2-amplified breast cancer: Prognostic and predictive impact Journal Article


Authors: Page, D. B.; Wen, H.; Brogi, E.; Dure, D.; Ross, D.; Spinelli, K. J.; Patil, S.; Norton, L.; Hudis, C.; McArthur, H. L.
Article Title: Monosomy 17 in potentially curable HER2-amplified breast cancer: Prognostic and predictive impact
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. © 2017, Springer Science+Business Media, LLC.
Keywords: immunohistochemistry; cancer chemotherapy; major clinical study; overall survival; drug efficacy; cancer staging; breast cancer; epidermal growth factor receptor 2; retrospective study; prediction; fluorescence in situ hybridization; gene dosage; estrogen receptor; progesterone receptor; trastuzumab; anthracycline; fish; chromosome 17; her2; monosomy; cancer prognosis; human epidermal growth factor receptor 2 positive breast cancer; human; female; priority journal; article; polysomy 17; monosomy 17; aneusomy 17; cep17; her2-amplified
Journal Title: Breast Cancer Research and Treatment
Volume: 167
Issue: 2
ISSN: 0167-6806
Publisher: Springer  
Date Published: 2018-01-01
Start Page: 547
End Page: 554
Language: English
DOI: 10.1007/s10549-017-4520-1
PROVIDER: scopus
PUBMED: 28986743
DOI/URL:
Notes: Article -- Export Date: 1 March 2018 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Sujata Patil
    386 Patil
  2. Clifford Hudis
    846 Hudis
  3. Larry Norton
    576 Norton
  4. Yong Hannah Wen
    118 Wen
  5. Edi Brogi
    305 Brogi
  6. Dara Stacy Ross
    43 Ross
  7. Dana C Dure
    3 Dure