Serum molecular signatures of weight change during early breast cancer chemotherapy.
OBJECTIVE
Weight gain in women receiving chemotherapy for breast cancer is associated with a higher risk of recurrence but its mechanisms are poorly understood.


METHODS
To investigate this, we assessed the metabolic, cytokine, and appetite-related peptide alterations during adjuvant chemotherapy for early breast cancer in postmenopausal women, and correlated these with body mass measurements. Specifically, we performed global metabolic profiling using (1)H-nuclear magnetic resonance spectroscopy of sequential sera, examined ghrelin immunoreactivity, RIAs for GLP-1 and peptide YY, and electrochemiluminescent cytokine analyses (tumor necrosis factor-alpha and interleukin-6) on sequential samples.


RESULTS
In those who gained >1.5 kg, several metabolite levels were positively associated with weight gain, specifically lactate, which was 63.5% greater in patients with increased body weight during chemotherapy compared with those with no weight gain (P < 0.01; the prespecified primary end point). A strong correlation (r = 0.7, P < 0.001) was detected between the rate of weight change and serum lactate levels, and on average, lactate levels exhibited the greatest metabolic response to chemotherapy, increasing by up to 75%. Normalized levels of peptide YY were also observed to be elevated in patients not gaining weight posttreatment (+30% compared with -7% for the weight gain group; P < 10(-4)). Baseline lactate, alanine, and body fat were all prognostic for weight gain (area under the receiver operator characteristic curves, >0.77; P < 0.05). No associations were observed between any other parameter and weight gain, including cytokine levels.


CONCLUSIONS
Metabonomics identifies excess energy expenditure pathways perturbed during chemotherapy for breast cancer, and establishes a significant association between serum lactate, body fat, and substantive weight gain during chemotherapy.
Keun
Hector C
HC
Department of Biomolecular Medicine, Imperial College, London, United Kingdom. h.keun@imperial.ac.uk
Sidhu
Jasmin
J
Pchejetski
Dmitry
D
Lewis
Jacqueline S
JS
Marconell
Helena
H
Patterson
Michael
M
Bloom
Steven R
SR
Amber
Vian
V
Coombes
R Charles
RC
Stebbing
Justin
J
D015415:Biomarkers / Q000032:analysis*; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D007773:Lactates / Q000097:blood; D019894:Peptide YY / Q000097:blood; D017698:Postmenopause; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015430:Weight Gain
D015415:Biomarkers; D015850:Interleukin-6; D007773:Lactates; D014409:Tumor Necrosis Factor-alpha; D019894:Peptide YY; D052216:Glucagon-Like Peptide 1