0

10

20

30

40

50

60

E+P+H- E+P+H+ E+P-H- E+P-H+ E-P+H- E-P+H+ E-P-H- E-P-H+

grade 1 grade 2 grade 3

Met

hods

% o

f pati

ents

Estrogen negativeEstrogen positive

ER+ PR+HER2-

double pos.

ER+ PR+HER2+

triple pos.

Hormone receptor @ grade 2

E+P+H- (69) Vs E+P+H+ (19)

Grade 2

Resu

ltsMetabolic phenotype of HER2 +/- grade 2 tumors

Can we identify unknowns?

100 200 m/z%

0

241.1024 M-15

147.

0657

189.

9976

257.1409 M+H

275.1654 Madd

then: CI_GCT

C5H6N2O2

PubChemChemSpiderCSLS DB

5-methyluracil3-methyluracil1-methyluracil…

Met

hods

Conc

lusi

on Metabolomics is mature for discovery research. ~15% CV. More than one platform is needed due to chemical diversity. Databases are essential.

Once new biomarker panels are established, clinical validation could use less sophisticated techniques.

Breast cancer tumors vastly differ metabolically from normal to grade 1-3 Triple negative tumors (ER-,PR-,HER2-) were mostly grade 3.

Metabolomics yields novel hypotheses on clinically relevant questions: Triple negative tumors have dysregulation of several metabolic modules: amino acids, nucleotide, membrane lipids and energy metabolism, plus salicylate and oligosaccharide metabolism.

Note: steady state levels may not change (pyruvate, free fatty acids, glutamine) although metabolic fluxes may be higher (as indicated in endpoint accumulations or products). More mechanistic insights by stable isotope studies.

Conclusion

European Union FP7 Health-2007-2.1.4.1 project 200327NIH R01 ES013932, R01 DK078328, RC2 GM092729, R01 HD058556

Thanks to fiehnlab.ucdavis.edu !Thanks to MetaCancer collaborators , PI Prof Carsten Denkert,

Charite Berlin, Germany