Kotoula, Vassiliki and Tsakiri, Kalliopi and Koliou, Georgia-Angeliki and Lazaridis, Georgios and Papadopoulou, Kyriaki and Giannoulatou, Eleni and Tikas, Ioannis and Christodoulou, Christos and Chatzopoulos, Kyriakos and Bobos, Mattheos and Pentheroudakis, George and Tsolaki, Eleftheria and Batistatou, Anna and Kotsakis, Athanassios and Koutras, Angelos and Linardou, Helena and Razis, Evangelia and Res, Eleni and Pectasides, Dimitrios and Fountzilas, George (2018) Relapsed and De Novo Metastatic HER2-positive Breast Cancer Treated With Trastuzumab: Tumor Genotypes and Clinical Measures Associated With Patient Outcome. Clinical Breast Cancer, ePub. ISSN 1526-8209 (Not OA)
Full text not available from this repository.Abstract
BACKGROUND:
We examined tumor genotype characteristics of human epidermal growth factor receptor 2 (HER2)-positive relapsed (R-) and de novo (dn-) metastatic breast cancer (MBC) in trastuzumab-treated patients who were previously not exposed to this agent.
MATERIALS AND METHODS:
We analyzed genotypes obtained upon deep sequencing from 113 HER2-positive primary tumors from 69 patients with R-MBC and 44 patients with dn-MBC.
RESULTS:
Mutations were observed in 90 (79.6%) tumors, 56 R-MBC and 34 dn-MBC (median number per tumor: 2; mean: 11.2; range: 0-150). The top mutated gene was TP53 (63.7%) followed by PIK3CA (24.8%) and others that were mostly co-mutated with TP53 (eg, 22 of 28 PIK3CA mutated tumors were co-mutated in TP53, 17 of these were R-MBC [P = .041]). dn-MBC had higher CEN17 average copies (P = .048). Tumor mutational burden inversely correlated with average HER2 copies (rho -0.32; P < .001). In all patients, PIK3CA mutations and higher proliferation rate were independent unfavorable prognosticators. In R-MBC, longer disease-free interval between initial diagnosis and relapse conferred lower risk for time-to-progression (P < .001) and death (P = .009); PIK3CA mutations conferred higher risk for death (P = .035). In dn-MBC, surgical removal of the primary tumor before any other therapy was favorable for time-to-progression (P = .002); higher tumor mutational burden was unfavorable for survival (P = .026).
CONCLUSIONS:
Except for the overall unfavorable prognostic effect of PIK3CA mutations in trastuzumab-treated MBC, our exploratory findings indicate that the outcome of patients with R-MBC is related to patient benefit from the preceding adjuvant chemotherapy and provide initial evidence that tumor mutational burden may be related to prognosis in dn-MBC, which is of potential clinical relevance and merits further investigation.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 18 Dec 2018 21:00 |
| Last Modified: | 18 Dec 2018 21:05 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/779 |
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