Relapsed and De Novo Metastatic HER2-positive Breast Cancer Treated With Trastuzumab: Tumor Genotypes and Clinical Measures Associated With Patient Outcome

Kotoula, Vassiliki; Tsakiri, Kalliopi; Koliou, Georgia-Angeliki; Lazaridis, Georgios; Papadopoulou, Kyriaki; Giannoulatou, Eleni; Tikas, Ioannis; Chatzopoulos, Kyriakos; Bobos, Mattheos; Pentheroudakis, George; Tsolaki, Eleftheria; Batistatou, Anna; Kotsakis, A.; Koutras, Angelos; Linardou, Helena; Razis, Evangelia; Res, Eleni; Pectasides, Dimitrios; Fountzilas, George

doi:10.1016/j.clbc.2018.10.014

Cited by 9 publications

(9 citation statements)

References 54 publications

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“…Based on the aforementioned reports, a higher number of mutations and mutated genes would be expected to associate with a higher TIL density and better survival. We observed such features with the same panel in a previous report by our Group in de novo but not in relapsed metastatic breast cancer (36). The impact of TMB on the outcome of patients with early breast cancer treated with adjuvant chemotherapy, as is the case for the present cohort, may not necessarily be the same as in various metastatic settings and needs to be elucidated.…”

Section: Discussionsupporting

confidence: 80%

Tumor Mutational Patterns and Infiltrating Lymphocyte Density in Young and Elderly Patients With Breast Cancer

Nikolaidi

Kotoula

Koliou

et al. 2020

Cancer Genomics Proteomics

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Background/Aim: Age may pertain to different tumor genotype characteristics which may interfere with treatment efficacy and prognosis. We investigated the distribution and prognostic effect of mutations and tumor infiltrating lymphocyte (stromal TIL density) in young (≤35 years) and elderly (>65 years) early breast cancer patients. Materials and Methods: Paraffin tumor genotypes of all clinical subtypes from 345 patients were examined. Results: A total of 638 mutations were detected in 221 patients (64.1%). Compared to young, elderly patients presented with lower TIL density (p<0.

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Section: Discussionsupporting

confidence: 80%

Tumor Mutational Patterns and Infiltrating Lymphocyte Density in Young and Elderly Patients With Breast Cancer

Nikolaidi

Kotoula

Koliou

et al. 2020

Cancer Genomics Proteomics

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“…Additionally, one recently published study that met the inclusion criteria was included after the initial database searching [29] . Consequently, 43 studies were included in this meta-analysis, consisting of 41 publications [ 8 , 9 , 11 , [13] , [14] , [15] , [16] , [17] , [18] , 20 , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] ]and two abstracts [ 60 , 61 ] ( Fig. 1 ).…”

Section: Resultsmentioning

confidence: 99%

Association of PIK3CA mutation with outcomes in HER2-positive breast cancer treated with anti-HER2 therapy: A meta-analysis and bioinformatic analysis of TCGA‑BRCA data

Chen,

Hu,

Wang

et al. 2023

Translational Oncology

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“…Interestingly, malignant progression of HER2-positive breast cancer is often characterized by aberrant PI3K/AKT activation [1,75,76]. For instance, PI3KCA mutations and a high proliferation rate are unfavourable prognostic factors in relapsed and de novo metastatic HER2-positive breast cancers treated with trastuzumab [77]. In addition, the loss of at least one copy of the PTEN gene is associated with a poor worse outcome in HER2-positive breast cancer, although it is not yet clear whether it is predictive of trastuzumab resistance [78,79].…”

Section: Discussionmentioning

confidence: 99%

DHA Affects Microtubule Dynamics Through Reduction of Phospho-TCTP Levels and Enhances the Antiproliferative Effect of T-DM1 in Trastuzumab-Resistant HER2-Positive Breast Cancer Cell Lines

D’Amico

Krasnowska

Manni³

et al. 2020

Cells

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Trastuzumab emtansine (T-DM1) is an anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugated to the microtubule-targeting agent emtansine (DM1). T-DM1 is an effective agent in the treatment of patients with HER2-positive breast cancer whose disease has progressed on the first-line trastuzumab containing chemotherapy. However, both primary and acquired tumour resistance limit its efficacy. Increased levels of the phosphorylated form of Translationally Controlled Tumour Protein (phospho-TCTP) have been shown to be associated with a poor clinical response to trastuzumab therapy in HER2-positive breast cancer. Here we show that phospho-TCTP is essential for correct mitosis in human mammary epithelial cells. Reduction of phospho-TCTP levels by dihydroartemisinin (DHA) causes mitotic aberration and increases microtubule density in the trastuzumab-resistant breast cancer cells HCC1954 and HCC1569. Combinatorial studies show that T-DM1 when combined with DHA is more effective in killing breast cells compared to the effect induced by any single agent. In an orthotopic breast cancer xenograft model (HCC1954), the growth of the tumour cells resumes after having achieved a complete response to T-DM1 treatment. Conversely, DHA and T-DM1 treatment induces a severe and irreversible cytotoxic effect, even after treatment interruption, thus, improving the long-term efficacy of T-DM1. These results suggest that DHA increases the effect of T-DM1 as poison for microtubules and supports the clinical development of the combination of DHA and T-DM1 for the treatment of aggressive HER2-overexpressing breast cancer.

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Relapsed and De Novo Metastatic HER2-positive Breast Cancer Treated With Trastuzumab: Tumor Genotypes and Clinical Measures Associated With Patient Outcome

Cited by 9 publications

References 54 publications

Tumor Mutational Patterns and Infiltrating Lymphocyte Density in Young and Elderly Patients With Breast Cancer

Tumor Mutational Patterns and Infiltrating Lymphocyte Density in Young and Elderly Patients With Breast Cancer

Association of PIK3CA mutation with outcomes in HER2-positive breast cancer treated with anti-HER2 therapy: A meta-analysis and bioinformatic analysis of TCGA‑BRCA data

DHA Affects Microtubule Dynamics Through Reduction of Phospho-TCTP Levels and Enhances the Antiproliferative Effect of T-DM1 in Trastuzumab-Resistant HER2-Positive Breast Cancer Cell Lines

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