Breast Reference Set Application: Chris Li-FHCRC (2013)

Abbreviated Name
Breast Ref Set App: Li (2013)
Lead Investigator
Li, Christopher — Fred Hutchinson Cancer Center
Coordinating Investigator
Zheng, Yingye — Fred Hutchinson Cancer Center
Involved Investigators

Abstract

No abstract availalbe.

Aims

Targeted LC-MS/MS: Electro-spray ionization (ESI) will be performed and MS acquisition will be performed in multiple reaction monitoring (MRM) mode following identical procedures used in past studies (21). An Agilent 6410 triple quad MS system equipped with an Agilent 1200 UPLC system will be utilized. Each MS acquisition for the serum samples (0.050 mL each) will target the 11-marker panel of metabolites, each of which has a 13C or D-labeled internal standard to provide for reliable quantitation of the absolute metabolite concentrations in blood. Appropriate separation conditions for positive and negative mode detection will be performed (21, 33). Data Analysis Plan: Welch’s t-tests will be performed to determine if observed differences in etabolite signal intensities between invasive cancer cases and benign disease without atypia controls reach statistical significance (p<0.05, corrected using the false discovery rate method). ROC curves will be generated for individual candidate markers to assess sensitivity and specificity at all possible marker cut-point levels.

Analytic Method

Targeted LC-MS/MS: Electro-spray ionization (ESI) will be performed and MS acquisition will be performed in multiple reaction monitoring (MRM) mode following identical procedures used in past studies (21). An Agilent 6410 triple quad MS system equipped with an Agilent 1200 UPLC system will be utilized. Each MS acquisition for the serum samples (0.050 mL each) will target the 11-marker panel of metabolites, each of which has a 13C or D-labeled internal standard to provide for reliable quantitation of the absolute metabolite concentrations in blood. Appropriate separation conditions for positive and negative mode detection will be performed (21, 33).

Outcome

This application proposes to use Reference Set #1. We request access to serum samples collected at the time of breast biopsy from subjects with IC (n=30) or benign disease without atypia (n=30). Statistical power: With 30 BC cases and 30 normal controls, a 25% difference in mean metabolite levels can be detected between groups with 80% power and α=0.05, assuming coefficients of variation of 30%, consistent with our past studies. These sample sizes appear sufficient to enable detection of changes similar in magnitude to those previously reported in pre-clinical (BC recurrence) specimens (20).

Publications

  • No publications available at this time for this protocol.

Biomarkers

Data Collections

  • No data collections available at this time for this protocol.
 Team Project
Start Date
Jan 8 2014
Estimated Finish Date
Feb 28 2014
Finish Date
Feb 28 2014
Protocol ID
383
Protocol Type
Reference Set
Fields of Research
  • Metabolomics
Collaborative Group
Breast and Gynecologic Cancers Research Group
Cancer Types
  • Malignant neoplasm of breast

Associated Forms