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Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment
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Comprehensive Analysis Identifies Variability in PI3K Pathway Alterations in Triple-Negative Breast Cancer Subtypes

Reva K Basho1, Li Zhao2, Jason B White2

  • 1Ellison Institute of Technology, Los Angeles, CA.

JCO Precision Oncology
|March 14, 2024
PubMed
Abstract

Insights

Alterations in the PI3K pathway are common in triple-negative breast cancer (TNBC) and impact treatment response. These genetic changes, particularly in M and LAR subtypes, may guide targeted therapy development for improved outcomes.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Triple-negative breast cancer (TNBC) exhibits frequent alterations in the PI3K pathway.
  • Mesenchymal (M) and Luminal Androgen Receptor (LAR) TNBC subtypes show a higher incidence of PI3K pathway alterations.
  • The specific impact of these alterations across diverse TNBC subtypes remains unclear.

Purpose of the Study:

  • To investigate the incidence of PI3K pathway alterations across distinct TNBC subtypes.
  • To correlate PI3K pathway alterations with pathologic response to neoadjuvant therapy (NAT) in TNBC patients.
  • To understand the clinical significance of PI3K pathway alterations in TNBC subtypes.

Main Methods:

  • Evaluated pretreatment tumor samples from 177 operable TNBC patients on a NAT clinical trial.
  • Classified tumors into seven TNBC subtypes using Pietenpol criteria.
  • Analyzed 32 PI3K pathway-activating genes for alterations (mutations, PTEN loss) via whole-exome sequencing, RNA sequencing, and immunohistochemistry.

Main Results:

  • Significant differences in PI3K pathway alteration incidence were observed across TNBC subtypes (P < .01).
  • LAR (81%), BL2 (79%), and M (62%) subtypes had the highest alteration rates.
  • PIK3CA mutation correlated with pathologic complete response (pCR) in the LAR subtype (P = .02).

Conclusions:

  • PI3K pathway alterations influence neoadjuvant therapy response in TNBC.
  • Targeted therapies hold promise for improving outcomes, especially in M and LAR TNBC patients.
  • Further research into PI3K pathway-targeted agents is warranted for specific TNBC subtypes.

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