Frequency of mesenchymal‐epithelial transition factor gene (<i>MET</i>) and the catalytic subunit of phosphoinositide‐3‐kinase (<i>PIK3CA</i>) copy number elevation and correlation with outcome in patients with early stage breast cancer

González-Angulo, Ana M.; Chen, Huiqin; Karuturi, Meghan Sri; Chávez-MacGregor, Mariana; Tsavachidis, Spyrus; Meric‐Bernstam, Funda; Anh, Kim; Hortobágyi, Gabriel N.; Thompson, Patricia A.; Mills, Gordon B.; Bondy, Melissa L.; Blumenschein, George R.

doi:10.1002/cncr.27608

Cited by 53 publications

(51 citation statements)

References 33 publications

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“…In agreement with other studies, increased MET copy number was shown to be inversely correlated with ER status [9, 20]. It was thereby inversely correlated with the luminal A subtype, the least aggressive of the breast cancer subtypes, indicating that Met is more prominent in more aggressive subtypes.…”

Section: Discussionsupporting

confidence: 91%

“…It is unclear what is causing this overexpression, a common cause is known to be gene amplification. Previous studies have failed to find MET amplification in breast cancer [20, 21]; the present study showed MET amplification in only 8% of the tumours of two cohorts, and amplification did not correlate with protein expression. Although protein expression did not correlate with poor prognosis, increased MET copy number tended in both cohorts to be indicative of a shortened distant and loco-regional recurrence-free survival.…”

Section: Discussioncontrasting

confidence: 87%

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Met and its ligand HGF are associated with clinical outcome in breast cancer

et al. 2016

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Few biomarkers exist to predict radiotherapy response in breast cancer. In vitro studies suggest a role for Met and its ligand HGF. To study this suggested role, MET and HGF gene copy numbers were determined by droplet digital PCR in tumours from 205 pre-menopausal and 184 post-menopausal patients, both cohorts randomised to receive either chemo- or radiotherapy. MET amplification was found in 8% of the patients in both cohorts and HGF amplification in 7% and 6% of the patients in the pre- and post-menopausal cohort, respectively. Met, phosphorylated Met (pMet), and HGF protein expression was determined by immunohistochemistry in the pre-menopausal cohort. Met, pMet, and HGF was expressed in 33%, 53%, and 49% of the tumours, respectively. MET amplification was associated with increased risk of distant recurrence for patients receiving chemotherapy. For the pre-menopausal patients, expression of cytoplasmic pMet and HGF significantly predicted benefit from radiotherapy in terms of loco-regional recurrence. Similar trends were seen for MET and HGF copy gain. In the post-menopausal cohort, no significant association of benefit from radiotherapy with neither genes nor proteins was found. The present results do not support that inhibition of Met prior to radiotherapy would be favourable for pre-menopausal breast cancer, as previously suggested.

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Section: Discussionsupporting

confidence: 91%

Section: Discussioncontrasting

confidence: 87%

Met and its ligand HGF are associated with clinical outcome in breast cancer

et al. 2016

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“…Li et al . also showed a negative outcome for patients with tumors harboring PIK3CA mutations[3, 12]. In contrast, Maruyama et al ., Perez-Tenorio et al , and Kalinsky et al .…”

Section: Introductionmentioning

confidence: 99%

Characterization of breast cancers with PI3K mutations in an academic practice setting using SNaPshot profiling

Abramson

Lloyd

Ballinger

et al. 2014

Breast Cancer Res Treat

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Purpose Mutations in the PIK3CA gene are common in breast cancer and represent a clinically useful therapeutic target. Several larger, population-based studies have shown a positive prognostic significance associated with these mutations. This study aims to further identify characteristics of patients harboring PIK3CA mutations while evaluating the clinical impact of genomic testing for these mutations. Methods Tumors from 312 patients at Vanderbilt-Ingram Cancer Center were analyzed for PIK3CA mutations using a multiplex screening assay (SNaPshot). Mutation rates, receptor status, histopathologic characteristics, and time to recurrence were assessed. The number of patients participating in clinical trials, specifically trials relating to the PIK3CA mutation, was examined. Statistically significant differences between wild type and mutated tumors were determined using the Wilcoxon, Pearson, and Fischer exact tests. Results The PIK3CA mutation was found in 25% of tumors tested. Patients with PIK3CA mutations were significantly more likely to express hormone receptors, be of lower combined histological grade, and have a reduced time to recurrence. Patients found to have a PIK3CA mutation were significantly more likely to enter a PIK3CA specific clinical trial. Conclusions In addition to confirming previously established positive prognostic characteristics of tumors harboring PIK3CA mutations, this study demonstrates the feasibility and utility of mutation profiling in a clinical setting. PIK3CA mutation testing impacted treatment and resulted in more patients entering mutation specific clinical trials.

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“…In both cohorts, MET and HGF were significantly correlated with each other (p<0.01). MET amplification has not been reported to be common in breast cancer, in the present study only 8% was found (Paper I) [138,139]. However, copy gain has been reported for MET in 27% HER2-positive metastatic breast cancer cases, as in the pre-and post-menopausal patients here, unrelated to subtype [140].…”

Section: Genes Of Interest In Breast Cancer Tumourscontrasting

confidence: 58%

“…Met and EGFR are reported to be involved in aggressive disease [138,153,156,[158][159][160]. An aggressive disease is indicated if the tumour is ER-negative, HER2-positive or triple-negative, and highly proliferative (as measured by NHG or S-phase fraction).…”

Section: Genes and Proteins In Relation To Clinicopathological Characmentioning

confidence: 99%

The receptor tyrosine kinase Met and the protein tyrosinephosphatase PTPN2 in breast cancer

Veenstra¹

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This thesis aimed to explore possible prognostic and predictive biomarkers in different subtypes and study their role in breast cancer. To this aid, breast cancer tumours of pre-and post-menopausal patients enrolled in two cohorts were analysed for gene copy numbers and expression of proteins involved in cell proliferation. Gene copy numbers of receptor tyrosine kinases MET and EGFR, Met's ligand HGF, and protein tyrosine phosphatase PTPN2 were determined by droplet digital PCR or quantitative PCR in both cohorts. Met, phosphorylated Met (pMet), HGF, and PTPN2 protein expression levels were analysed with immunohistochemical staining in the pre-menopausal cohort. Moreover, the role of the aforementioned proteins was investigated in breast cancer cell lines.Amplification of MET, HGF, and EGFR in breast tissues was found to be low (5-8%). These three genes, all located on chromosome 7, were found to be strongly correlated with each other and to be associated with shortened distant recurrence-free survival. High protein expression of Met, pMet, and HGF was found in 33%, 53%, and 49% of the breast tumours. MET and EGFR were found to be more often amplified in TNBC disease, correlating with worse survival.Moreover, stromal expression of HGF was associated with shorter survival in TNBC. EGF stimulation in TNBC cell line MDA-MB-468 led to inhibited cell

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Frequency of mesenchymal‐epithelial transition factor gene (MET) and the catalytic subunit of phosphoinositide‐3‐kinase (PIK3CA) copy number elevation and correlation with outcome in patients with early stage breast cancer

Cited by 53 publications

References 33 publications

Met and its ligand HGF are associated with clinical outcome in breast cancer

Met and its ligand HGF are associated with clinical outcome in breast cancer

Characterization of breast cancers with PI3K mutations in an academic practice setting using SNaPshot profiling

The receptor tyrosine kinase Met and the protein tyrosinephosphatase PTPN2 in breast cancer

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