Exploration of serum metabolomic profiles and outcomes in women with metastatic breast cancer: a pilot study.
BACKGROUND
Metabolomics, a global study of metabolites and small molecules, is a novel expanding field. In this pilot study, metabolomics has been applied to serum samples from women with metastatic breast cancer to explore outcomes and response to treatment.


METHODS
Pre-treatment and serial on-treatment serum samples were available from an international clinical trial in which 579 women with metastatic breast cancer were randomized to paclitaxel plus either a targeted anti-HER2 treatment (lapatinib) or placebo. Serum metabolomic profiles were obtained using 600 MHz nuclear magnetic resonance spectroscopy. Profiles were compared with time to progression, overall survival and treatment toxicity.


RESULTS
Pre- and on-treatment serum samples were assessed for over 500 patients. Unbiased metabolomic profiles in the biologically unselected overall trial population did not correlate with outcome or toxicity. In a subgroup of patients with HER2-positive disease treated with paclitaxel plus lapatinib, metabolomic profiles from patients in the upper and lower thirds of the dataset showed significant differences for time to progression (N = 22, predictive accuracy = 89.6%) and overall survival (N = 16, predictive accuracy = 78.0%).


CONCLUSIONS
In metastatic breast cancer, metabolomics may play a role in sub selecting patients with HER2 positive disease with greater sensitivity to paclitaxel plus lapatinib.
Magnetic Resonance Center (CERM), University of Florence, Via L. Sacconi 6, 50019 Sesto Fiorentino, Italy.
Leonardo
L
Tenori
Catherine
C
Oakman
Wederson M
WM
Claudino
Patrizia
P
Bernini
Silvia
S
Cappadona
Stefano
S
Nepi
Laura
L
Biganzoli
Michael C
MC
Arbushites
Claudio
C
Luchinat
Ivano
I
Bertini
Angelo
A
Di Leo
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism*; D017326:Clinical Trials, Phase III as Topic; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077341:Lapatinib; D055442:Metabolome; D055432:Metabolomics; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000627:therapeutic use; D010865:Pilot Projects; D011799:Quinazolines / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
D000077341:Lapatinib; D017239:Paclitaxel; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human