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Prognostic Impact of Src, CDKN1B, and JAK2 Expression in Metastatic Breast Cancer Patients Treated with Trastuzumab

Panagiota Economopoulou1, Vassiliki Kotoula2, Georgia-Angeliki Koliou3

  • 1Second Department of Internal Medicine, Attikon University Hospital, 1 Rimini St 12462, Haidari, Athens, Greece.

Translational Oncology
|March 17, 2019
PubMed
Abstract

Insights

Low CDKN1B and JAK2 mRNA expression are unfavorable prognostic factors in metastatic breast cancer patients treated with trastuzumab. These biomarkers may predict trastuzumab resistance, suggesting distinct pathways in de novo and relapsed disease.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biomarker Research

Background:

  • Src, CDKN1B, and JAK2 are key in cell signaling.
  • Their prognostic significance in HER2-positive metastatic breast cancer (MBC) treated with trastuzumab (T) is investigated.

Purpose of the Study:

  • To evaluate the prognostic value of Src, CDKN1B, and JAK2 in HER2-positive MBC patients receiving trastuzumab.
  • To explore their potential role in trastuzumab resistance.

Main Methods:

  • Retrospective analysis of 197 HER2-positive MBC patients treated with T.
  • Assessment of protein expression (ER, PgR, Ki67, HER2, PTEN), EGFR amplification, PI3KCA mutations, and TILs.
  • Quantification of Src, CDKN1B, and JAK2 mRNA expression via RT-qPCR.

Main Results:

  • Low CDKN1B mRNA expression correlated with higher progression risk in HER2-positive patients (HR=1.58).
  • Low Src was linked to longer survival in HER2-negative patients (HR=0.56).
  • Low CDKN1B and JAK2 mRNA expression were unfavorable prognostic factors for progression-free survival in de novo and relapsed MBC, respectively.

Conclusions:

  • Low CDKN1B and JAK2 mRNA expression are unfavorable prognosticators in trastuzumab-treated MBC.
  • CDKN1B and JAK2 may serve as prognostic factors for trastuzumab resistance.
  • Distinct pathways may be involved in trastuzumab resistance in de novo versus relapsed MBC.

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