Background: HER2 positive breast cancer (HER2+ BC) is a heterogeneous disease. Presenting features, patterns of recurrence and survival of HER2+ BC can differ according to hormone receptors (HR) status. The purpose of this study is to highlight different gene profile and molecular pathways between HR+ and HR- metastatic HER2+ BCs. Materials and methods: 34 HER2+ metastatic BC patients were included: 18 patients with HR+/HER2+ and 14 with HR-/HER2+. Data regarding tumor characteristics, treatment information and clinical outcomes were collected. The expression of 770 genes and 13 molecular pathways were evaluated by means of Nanostring PanCancer pathway panel performed on BC formalin-fixed paraffin-embedded tissues from diagnostic core biopsy or surgical resection specimen. Results: Gene expression analysis identified 118 genes with significantly different expression in the two cohorts. All but one of these genes were over-expressed; only the gene CACNG6 was down-regulated in HR+/HER2+ group. In particular, 93 genes were over-expressed in HR-/HER2+ while 24 were overexpressed in HR+/HER2+. Most of these genes encoded growth factors, pro- or anti-inflammatory interleukins and DNA repair factors. 62% of these genes were involved in PI3K, MAPK and RAS pathways (32, 22 and 18, respectively). PI3K, MAPK and NOTCH pathways were differently expressed between HR+/HER2+ and HR-/HER2 + (p = 0.003, p = 0.0018, p = 0.02, respectively). All these three pathways were overexpressed in HR-/HER2+ BC. In particular, all the significantly different expression genes in NOTCH pathways were overexpressed in HR-/HER2+ group. Conclusions: This genome expression analysis identified a gene expression profile able to differentiate HR+ versus HR- HER2+ metastatic BC. The overexpression of PI3K, MAPK and NOTCH pathways in HR-/HER2+ BC could justify its more aggressive behaviour. The validation of this HER2+ BC profile needs further investigation.

Differential gene expression patterns in HER2 positive metastatic breast cancer patients according to hormone receptor status / Omarini, C; Kaleci, S; Guaitoli, G; Bettelli, S; Caprera, Cecilia; Manfredini, S; Caggia, F; Baschieri, Cristina; Moscetti, Luca; Maiorana, A; Cascinu, S; Piacentini, F. - In: ANNALS OF ONCOLOGY. - ISSN 0923-7534. - 28:Issue suppl_6(2017).

Differential gene expression patterns in HER2 positive metastatic breast cancer patients according to hormone receptor status.

C Omarini;S Kaleci;G Guaitoli;S Bettelli;S Manfredini;F Caggia;Baschieri Cristina;A Maiorana;S Cascinu;F Piacentini
2017

Abstract

Background: HER2 positive breast cancer (HER2+ BC) is a heterogeneous disease. Presenting features, patterns of recurrence and survival of HER2+ BC can differ according to hormone receptors (HR) status. The purpose of this study is to highlight different gene profile and molecular pathways between HR+ and HR- metastatic HER2+ BCs. Materials and methods: 34 HER2+ metastatic BC patients were included: 18 patients with HR+/HER2+ and 14 with HR-/HER2+. Data regarding tumor characteristics, treatment information and clinical outcomes were collected. The expression of 770 genes and 13 molecular pathways were evaluated by means of Nanostring PanCancer pathway panel performed on BC formalin-fixed paraffin-embedded tissues from diagnostic core biopsy or surgical resection specimen. Results: Gene expression analysis identified 118 genes with significantly different expression in the two cohorts. All but one of these genes were over-expressed; only the gene CACNG6 was down-regulated in HR+/HER2+ group. In particular, 93 genes were over-expressed in HR-/HER2+ while 24 were overexpressed in HR+/HER2+. Most of these genes encoded growth factors, pro- or anti-inflammatory interleukins and DNA repair factors. 62% of these genes were involved in PI3K, MAPK and RAS pathways (32, 22 and 18, respectively). PI3K, MAPK and NOTCH pathways were differently expressed between HR+/HER2+ and HR-/HER2 + (p = 0.003, p = 0.0018, p = 0.02, respectively). All these three pathways were overexpressed in HR-/HER2+ BC. In particular, all the significantly different expression genes in NOTCH pathways were overexpressed in HR-/HER2+ group. Conclusions: This genome expression analysis identified a gene expression profile able to differentiate HR+ versus HR- HER2+ metastatic BC. The overexpression of PI3K, MAPK and NOTCH pathways in HR-/HER2+ BC could justify its more aggressive behaviour. The validation of this HER2+ BC profile needs further investigation.
28
Omarini, C; Kaleci, S; Guaitoli, G; Bettelli, S; Caprera, Cecilia; Manfredini, S; Caggia, F; Baschieri, Cristina; Moscetti, Luca; Maiorana, A; Cascinu, S; Piacentini, F
Differential gene expression patterns in HER2 positive metastatic breast cancer patients according to hormone receptor status / Omarini, C; Kaleci, S; Guaitoli, G; Bettelli, S; Caprera, Cecilia; Manfredini, S; Caggia, F; Baschieri, Cristina; Moscetti, Luca; Maiorana, A; Cascinu, S; Piacentini, F. - In: ANNALS OF ONCOLOGY. - ISSN 0923-7534. - 28:Issue suppl_6(2017).
File in questo prodotto:
File Dimensione Formato  
Differential gene expression patterns in HER2 positive metastatic breast.pdf

accesso aperto

Tipologia: Versione dell'editore (versione pubblicata)
Dimensione 68.23 kB
Formato Adobe PDF
68.23 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1153017
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? 0
social impact