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09.08.2018 | Original Article | Ausgabe 5/2018

Virchows Archiv 5/2018

Activating human epidermal growth factor receptor 2 (HER2) gene mutation in bone metastases from breast cancer

Zeitschrift:
Virchows Archiv > Ausgabe 5/2018
Autoren:
Matthias Christgen, Stephan Bartels, Angelina Luft, Sascha Persing, Daniel Henkel, Ulrich Lehmann, Hans Kreipe
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s00428-018-2414-1) contains supplementary material, which is available to authorized users.
Matthias Christgen and Stephan Bartels contributed equally to this work.

Abstract

In addition to amplification, point mutations of the human epidermal growth factor receptor 2 (HER2) gene (ERBB2) have been shown to activate the corresponding signaling pathway in breast cancer. The prevalence of ERBB2/HER2 mutation in bone metastasis of breast cancer and the associated phenotype are not known. In this study, bone metastases from breast cancer patients (n = 231) were analyzed for ERBB2/HER2 mutation. In 7 patients (3%; median age 70 years, range 50–83 years), gain-of-function mutations of ERBB2/HER2 were detected. The most frequent mutation was p.L755S (71%). In 29% of mutated cases, p.V777L was found. Lobular breast cancer was present in 71% of mutated cases (n = 5) and in 49% of all samples (n = 231; p = 0.275). Mutation frequency was 4.4% in the lobular subgroup and 17.4% in the pleomorphic subtype of lobular cancer (n = 23), respectively. All but one mutated lobular cancers were of the pleomorphic subtype (p = 0.006). Mutated cancers belonged either to the luminal (n = 4) or to the triple-negative types (n = 3). With regard to protein expression and gene amplification, HER2 was negative in all mutated cases. Among the 14% of metastatic luminal cancers with estrogen receptor gene (ESR1) mutation, conveying resistance against aromatase inhibitors, no concomitant ERBB2/HER2 mutation occurred. We conclude that activating HER2 mutation is present in about 3% of bone metastases from breast cancers, with significantly higher rates in the pleomorphic subtype of lobular cancer. Since mutated cases appear to be HER2-negative by conventional testing, the opportunity for specific anti-HER2 therapy may be missed.

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Zusatzmaterial
ESM 1 (DOCX 15 kb)
428_2018_2414_MOESM1_ESM.docx
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