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Differential molecular pathways expression in HER2 positive early breast cancer according to hormone receptor status

  • Claudia OmariniEmail author
  • Stefania Bettelli
  • Cecilia Caprera
  • Samantha Manfredini
  • Monica Barbolini
  • Luca Moscetti
  • Chrystel Isca
  • Angela Toss
  • Elena Barbieri
  • Laura Cortesi
  • Shaniko Kaleci
  • Antonino Maiorana
  • Giovanni Tazzioli
  • Stefano Cascinu
  • Federico Piacentini
Original Article – Cancer Research
  • 57 Downloads

Abstract

Purpose

Hormone receptors (HR) status in HER2 + breast cancer (BC) is a recognized stratification factor with relevant clinical implication. According to HR expression, HER2 + BC show different clinical characteristics, treatment sensitivity and prognosis. The interaction between HR and HER2 pathways remains incompletely understood.

Methods

Thirty-four HER2 + BC were included: 18 tumors with HER2+/HR + and 16 with HER2+/HR−. The expression of 770 genes and 13 molecular pathways were evaluated using Nanostring PanCancer Pathway panel performed on FFPE BC biopsies.

Results

Gene expression analysis identified 127 genes with significantly different expression between the two cohorts. 83% of these genes were overexpressed in HER2+/HR− cohort. Globally, 23% of them belonged to PI3K pathway (41 genes), 15% to Trascriptional regulation (26 genes) and 12% to MAPK (22 genes). Regarding pathway expression, PI3K, MAPK and NOTCH were significantly differently expressed between the two groups (p = 0.003, p = 0.0018 and p = 0.02, respectively), all of them were overexpressed in HER2+/HR− tumors.

Conclusions

According to HR status, HER2 + tumors express different pathways profiles: the overexpression of PI3K, MAPK and NOTCH pathways in HER2+/HR− group could justify different survival outcomes and treatment sensitivity. The identification of tumor driver pathways may be a useful instrument for individualized pathway-directed therapies. Further clinical implications are warranted.

Keywords

HER2 positive Trastuzumab PI3K MAPK Molecular pathways 

Notes

Funding

This study was funded by Progetto Ricerca Finalizzata 2009 (RF 2009-1472600).

Compliance with ethical standards

Conflict of interest

No potential conflicts of interest were declared.

Ethics approval and consent to participate

The Ethical Committee of Azienda Ospedaliero Universitaria Policlinico di Modena approved this study (protocol number: CE 267/15). All patients signed a written, informed consent.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Claudia Omarini
    • 1
    Email author return OK on get
  • Stefania Bettelli
    • 2
  • Cecilia Caprera
    • 2
  • Samantha Manfredini
    • 2
  • Monica Barbolini
    • 1
  • Luca Moscetti
    • 1
  • Chrystel Isca
    • 1
  • Angela Toss
    • 1
  • Elena Barbieri
    • 1
  • Laura Cortesi
    • 1
  • Shaniko Kaleci
    • 2
  • Antonino Maiorana
    • 2
  • Giovanni Tazzioli
    • 3
  • Stefano Cascinu
    • 1
  • Federico Piacentini
    • 1
  1. 1.Division of Medical Oncology, Department of Medical and Surgical Sciences for Children and AdultsUniversity Hospital of ModenaModenaItaly
  2. 2.Division of Pathological Anatomy, Department of Diagnostic, Clinical Medicine and Public HealthUniversity Hospital of ModenaModenaItaly
  3. 3.Oncologic Breast Surgery Unit, Department of Medical and Surgical Sciences for Children and AdultsUniversity Hospital of ModenaModenaItaly

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