Frequent alterations of HER2 through mutation, amplification, or overexpression in pleomorphic lobular carcinoma of the breast.

Abstract

Mutations in HER2 gene have been identified in a small subset of breast cancer cases. Identification of HER2 mutation has therapeutic implications for breast cancer, but whether a subgroup of breast cancer with a higher frequency of HER2 mutation exists, remains unknown. We analyzed HER2 mutation and pathologic factors on 73 formalin-fixed, paraffin-embedded samples, including 21 pleomorphic invasive lobular carcinoma (p-ILC) cases, 3 pleomorphic lobular carcinoma in situ (p-LCIS) cases, and 49 classic invasive lobular carcinoma (c-ILC) cases. Mutations were identified through direct sequencing. HER2 overexpression and amplification were determined through immunohistochemistry and fluorescent in situ hybridization. Six mutations were identified, including five in the 24 p-ILC or p-LCIS (p-ILC/p-LCIS) cases (20.8 %) and one in the 49 c-ILC cases (2.0 %), and the difference in frequency was significant (p = 0.013). Eight of the 24 (33.3 %) p-ILC/p-LCIS cases exhibited HER2 amplification or overexpression (amplification/overexpression), which was significantly higher than in the c-ILC cases (1/49, 2 %). Mutation and amplification/overexpression were mutually exclusive. HER2 mutations were identified more frequently in the p-ILC/p-LCIS cases with extensive apocrine change (p = 0.018). Combined HER2 alterations through mutation or amplification/overexpression were more frequently identified in p-ILC/p-LCIS cases without estrogen receptor expression. The high frequency (54.1 %, 13/24) of combined HER2 alterations in the p-ILC/p-LCIS cases suggests a crucial role of HER2 in the pathogenesis of p-ILC/p-LCIS. Because of the reported responsiveness of HER2 mutation to anti-HER2 therapy, p-ILC patients without HER2 amplification/overexpression should receive HER2 mutation analysis to identify this therapeutically relevant target.

• Authors: Huang-Chun Lien, Yu-Ling Chen, Yu-Lin Juang, Yung-Ming Jeng
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 150 Issue 2 Pg. 447-55 (Apr 2015) ISSN: 1573-7217 [Electronic] Netherlands
• PMID: 25773929 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ERBB2 protein, human
• Receptor, ErbB-2

Topics

• Base Sequence
• Breast Neoplasms (genetics, metabolism, pathology)
• Carcinoma, Lobular (genetics, metabolism, pathology)
• DNA Mutational Analysis
• Female
• Gene Amplification
• Gene Expression
• Gene Frequency
• Humans
• Mutation
• Receptor, ErbB-2 (genetics)