Level of HER2/neu amplification in primary tumours and metastases in HER2-positive breast cancer and survival after trastuzumab therapy.

Giuseppe Gullo, Daniela Bettio, Monica Zuradelli, Giovanna Masci, Laura Giordano, Claudia Bareggi, Maurizio Tomirotti, Piermario Salvini, Letterio Runza, Nicla La Verde, Armando Santoro

Oncology Department, St Vincent's University Hospital, Merrion Road, Dublin, Ireland. g.gullo@svuh.ie

Breast (Edinburgh, Scotland) 2013 Apr

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The level of HER2/neu amplification may vary widely in breast cancers with HER2/neu alteration. The clinical significance of this phenomenon is still unclear. This study was aimed to explore the level of HER2/neu amplification in primary tumours and metastases in HER2-positive metastatic breast cancer (MBC) and its potential impact on survival after a trastuzumab-containing therapy. We retrospectively identified MBC patients treated with a trastuzumab-containing therapy and performed dual-colour FISH on tumour samples from either primary tumour and/or metastasis in a central laboratory. We retrieved 110 tumour samples from 91 patients and included 79 tumour samples (primary = 56; metastasis = 23) from 63 patients in the final analysis. We found higher level of HER2/neu amplification in the metastases than in the primary tumours (median HER2/CEP17 ratio: 10.5 vs. 7.0, respectively). In 69% of patients (n = 16) with two tumour samples, the level of HER2/neu amplification was higher in the metastasis than in the paired primary tumour (median HER2/CEP17 ratio: 10.9 vs. 8.3, respectively, p = 0.004). The incremental gain in level of HER2/neu amplification was associated with significantly shorter OS after trastuzumab-containing therapy (p = 0.023, HR 1.014, CI95%: 1.002-1.025). The level of HER2/neu amplification tends to increase from the primary tumour to the paired metastases in a significant proportion of patients with HER2-positive MBC. This phenomenon, although still not completely understood, could lead to a shorter OS after trastuzumab therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

Citation

Giuseppe Gullo, Daniela Bettio, Monica Zuradelli, Giovanna Masci, Laura Giordano, Claudia Bareggi, Maurizio Tomirotti, Piermario Salvini, Letterio Runza, Nicla La Verde, Armando Santoro. Level of HER2/neu amplification in primary tumours and metastases in HER2-positive breast cancer and survival after trastuzumab therapy. Breast (Edinburgh, Scotland). 2013 Apr;22(2):190-3