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Increased PI3K pathway activity is associated with recurrent breast cancer in patients with low and intermediate 21-gene recurrence score

  • 0Department of Pathology, New York University Langone Health and Grossman School of Medicine, New York, New York, USA.
Journal of Clinical Pathology +

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February 21, 2024

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February 21, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Increased PI3K pathway activity, not PIK3CA mutations, may predict recurrence in early-stage breast cancer with low or intermediate 21-gene recurrence scores. This finding aids in identifying high-risk patients for better treatment strategies.

Area Of Science

  • Oncology
  • Molecular Biology
  • Genetics

Background

  • Early-stage breast cancer with low or intermediate 21-gene recurrence scores (RS) presents a challenge for predicting recurrence risk.
  • Identifying molecular drivers of recurrence in this patient group is crucial for personalized treatment.

Purpose Of The Study

  • To investigate the activity of key signaling pathways (ER, AR, PI3K, MAPK) and mutational status in early-stage breast carcinomas.
  • To identify molecular features that predict recurrence in patients with low and intermediate 21-gene RS.

Main Methods

  • Retrospective case-control study of 18 recurrent and 15 non-recurrent breast cancer patients with low/intermediate 21-gene RS.
  • Assessed mRNA expression of ER, AR, PI3K, and MAPK pathways using qPCR.
  • Analyzed tumor mutational landscape via targeted DNA sequencing.

Main Results

  • PI3K pathway activity was significantly higher in recurrent cases (p=0.0014) and predicted recurrence (AUC=0.79).
  • No significant differences in ER, AR, or MAPK pathway activity were observed.
  • PIK3CA mutations were common but not associated with recurrence or PI3K pathway activity; higher Ki67 expression correlated with recurrence (p=0.042).

Conclusions

  • Increased PI3K pathway activity, independent of PIK3CA mutations, may contribute to recurrence in early-stage breast cancer with low/intermediate 21-gene RS.
  • Pathway analysis, particularly PI3K activity, can help identify high-risk patients within this subgroup.

Keywords:

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