Association of PI3K Pathway Mutations with Early Positron-Emission Tomography/CT Imaging Response after Radioembolization for Breast Cancer Liver Metastases: Results of a Single-Center Retrospective Pilot Study

J Vasc Interv Radiol. 2018 Sep;29(9):1226-1235. doi: 10.1016/j.jvir.2018.04.018. Epub 2018 Aug 3.

Abstract

Purpose: To describe imaging response and survival after radioembolization for metastatic breast cancer and to delineate genetic predictors of imaging responses and outcomes.

Materials and methods: This retrospective study included 31 women (average age, 52 y) with liver metastasis from invasive ductal carcinoma who underwent resin and glass radioembolization (average cumulative dose, 2.0 GBq ± 1.8) between January 2011 and September 2017 after receiving ≥ 3 lines of chemotherapy. Twenty-four underwent genetic profiling with MSK-IMPACT or Sequenom; 26 had positron-emission tomography (PET)/CT imaging before and after treatment. Survival after the first radioembolization and 2-4-month PET/CT imaging response were assessed. Laboratory and imaging features were assessed to determine variables predictive of outcomes. Unpaired Student t tests and Fisher exact tests were used to compare responders and nonresponders categorized by changes in fluorodeoxyglucose avidity. Kaplan-Meier survival analysis was used to determine the impact of predictors on survival after radioembolization.

Results: Median survival after radioembolization was 11 months (range, 1-49 mo). Most patients (18 of 26; 69%) had complete or partial response based on changes in fluorodeoxyglucose avidity. Imaging response was associated with longer survival (P = .005). Whereas 100% of patients with PI3K pathway mutations showed an imaging response, only 45% of wild-type patients showed a response (P = .01). Median survival did not differ between PI3K pathway wild-type (10.9 mo) and mutant (undefined) patients (P = .50).

Conclusions: These preliminary data suggest that genomic profiling may predict which patients with metastatic breast cancer benefit most from radioembolization. PI3K pathway mutations are associated with improved imaging response, which is associated with longer survival.

MeSH terms

  • Adult
  • Breast Neoplasms / diagnostic imaging*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Clinical Decision-Making
  • DNA Mutational Analysis
  • Embolization, Therapeutic / adverse effects
  • Embolization, Therapeutic / methods*
  • Female
  • Gene Expression Profiling
  • Humans
  • Liver Neoplasms / diagnostic imaging*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / secondary
  • Liver Neoplasms / surgery*
  • Middle Aged
  • Mutation*
  • New York City
  • Patient Selection
  • Phosphatidylinositol 3-Kinases / genetics*
  • Pilot Projects
  • Positron Emission Tomography Computed Tomography*
  • Precision Medicine
  • Predictive Value of Tests
  • Preliminary Data
  • Radiopharmaceuticals / administration & dosage*
  • Radiopharmaceuticals / adverse effects
  • Retrospective Studies
  • Risk Factors
  • Signal Transduction / genetics
  • Time Factors
  • Treatment Outcome

Substances

  • Radiopharmaceuticals
  • Phosphatidylinositol 3-Kinases