Quantitative HER2 and p95HER2 levels in primary breast cancers and matched brain metastases

Duchnowska, Renata; Sperinde, Jeff; Chenna, Ahmed; Huang, Weidong; Weidler, Jodi; Winslow, John; Haddad, Mojgan; Paquet, Agnès; Yang, Lie; Trojanowski, Tomasz; Mandat, Tomasz; Kowalczyk, Anna; Czartoryska-Arłukowicz, Bogumiła; Radecka, Barbara; B, Jarosz; Staszkiewicz, Rafał; Kalinka, Ewa; Chudzik, Małgorzata; Biernat, Wojciech; Jassem, Jacek

doi:10.1093/neuonc/nov012

Cited by 21 publications

(29 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We postulate that the neuregulin‐rich brain microenvironment also contributes to therapeutic resistance in BMs. HER2 and HER3 are induced in BMs from breast and lung cancers and our data suggest that this is an adaptive response to paracrine ligands (see supplementary material, Figure S13), since most BMs lacked expression of NRG RNA. Neuregulin‐1 mediates resistance to cisplatin therapy in mouse models of non‐small cell lung cancer and this may also be relevant in BMs, which are essentially treatment‐refractory manifestations of cancer arising in a neuregulin‐rich microenvironment.…”

Section: Discussionmentioning

confidence: 77%

“…There is a growing body of literature implicating the ERBB /HER pathway activation in development of BMs . Therefore, taking a candidate approach, we analysed mutation, copy‐number and expression of key ERBB /HER pathway members (Figure A; see also supplementary material, Figures S5, S6, S9, S10).…”

Section: Resultsmentioning

confidence: 99%

“…The ERBB/HER pathway has also been implicated in BM development, particularly the tyrosine kinase receptors EGFR, HER2 and HER3 [7,29,[32][33][34][35]. These receptors engage in ligand-induced dimerization, activating downstream signalling through the PI3K-AKT, PLCγ-PKC, STAT and Ras-MAPK pathways.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Integrated genomic and transcriptomic analysis of human brain metastases identifies alterations of potential clinical significance

Saunus

Quinn

Patch

et al. 2015

The Journal of Pathology

105

103

View full text Add to dashboard Cite

Treatment options for patients with brain metastases (BMs) have limited efficacy and the mortality rate is virtually 100%. Targeted therapy is critically under-utilized, and our understanding of mechanisms underpinning metastatic outgrowth in the brain is limited. To address these deficiencies, we investigated the genomic and transcriptomic landscapes of 36 BMs from breast, lung, melanoma and oesophageal cancers, using DNA copy-number analysis and exome-and RNA-sequencing. The key findings were as follows.

show abstract

Section: Discussionmentioning

confidence: 77%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Integrated genomic and transcriptomic analysis of human brain metastases identifies alterations of potential clinical significance

Saunus

Quinn

Patch

et al. 2015

The Journal of Pathology

105

103

View full text Add to dashboard Cite

show abstract

“…Evidence shows that several primary breast cancers, originally negative for HER2, were HER2 positive after metastasizing to the brain (6).Quantitative analysis of matched primary and BCBM tumors for HER2 and truncated HER2 (p95HER2) showed that there was a 2.1 fold increase in HER2 and a 1.5 fold increase in p95HER2 expression from the primary breast tumor to the brain metastasis (111). Additionally, CTCs from BCBM patients were assessed for HER2 expression by antibody based analysis and RT-PCR.…”

Section: Correlative Studiesmentioning

confidence: 99%

EGFR and HER2 signaling in breast cancer brain metastasis

et al. 2016

View full text Add to dashboard Cite

Breast cancer occurs in approximately 1 in 8 women and 1 in 37 women with breast cancer succumbed to the disease. Over the past decades, new diagnostic tools and treatments have substantially improved the prognosis of women with local diseases. However, women with metastatic disease still have a dismal prognosis without effective treatments. Among different molecular subtypes of breast cancer, the HER2-enriched and basal-like subtypes typically have higher rates of metastasis to the brain. Basal-like metastatic breast tumors frequently express EGFR. Consequently, HER2-and EGFR-targeted therapies are being used in the clinic and/or evaluated in clinical trials for treating breast cancer patients with brain metastases. In this review, we will first provide an overview of the HER2 and EGFR signaling pathways. The roles that EGFR and HER2 play in breast cancer metastasis to the brain will then be discussed. Finally, we will summarize the preclinical and clinical effects of EGFR-and HER2-targeted therapies on breast cancer metastasis.

show abstract

“…Quantitative analysis of matched primary and BCBM tumors for HER2 and truncated HER2 (p95HER2) showed that there was a 2.1 fold increase in HER2 and a 1.5 fold increase in p95HER2 expression from the primary breast tumor to the brain metastasis (111). Additionally, CTCs from BCBM patients were assessed for HER2 expression by antibody based analysis and RT-PCR.…”

Section: Role Of Her2 In Breast Cancer Brain Metastasismentioning

confidence: 99%

EGFR and HER2 signaling in breast cancer brain metastasis

et al. 2016

View full text Add to dashboard Cite

Breast cancer occurs in approximately 1 in 8 women and 1 in 37 women with breast cancer succumbed to the disease. Over the past decades, new diagnostic tools and treatments have substantially improved the prognosis of women with local diseases. However, women with metastatic disease still have a dismal prognosis without effective treatments. Among different molecular subtypes of breast cancer, the HER2-enriched and basal-like subtypes typically have higher rates of metastasis to the brain. Basal-like metastatic breast tumors frequently express EGFR. Consequently, HER2- and EGFR-targeted therapies are being used in the clinic and/or evaluated in clinical trials for treating breast cancer patients with brain metastases. In this review, we will first provide an overview of the HER2 and EGFR signaling pathways. The roles that EGFR and HER2 play in breast cancer metastasis to the brain will then be discussed. Finally, we will summarize the preclinical and clinical effects of EGFR- and HER2-targeted therapies on breast cancer metastasis.

show abstract

Quantitative HER2 and p95HER2 levels in primary breast cancers and matched brain metastases

Abstract: This is the first study of quantitative p95 and HER2 expression in matched PBC and BM. BM of breast cancer shows significant increases in expression of both biomarkers compared with matched PBC. These data provide a rationale for future correlative studies on p95 and HER2 levels in BM.

Cited by 21 publications

References 48 publications

Integrated genomic and transcriptomic analysis of human brain metastases identifies alterations of potential clinical significance

Integrated genomic and transcriptomic analysis of human brain metastases identifies alterations of potential clinical significance

EGFR and HER2 signaling in breast cancer brain metastasis

EGFR and HER2 signaling in breast cancer brain metastasis

Contact Info

Product

Resources

About