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Abstract
BackgroundPrecision medicine in breast cancer demands markers sensitive to early treatment response. Aerobic glycolysis (AG) upregulates lactate dehydrogenase A (LDH-A) with elevated lactate production; however, existing approaches for lactate quantification are either invasive or impractical clinically.MethodsThirty female patients (age 39–78 years, 15 grade II and 15 grade III) with invasive ductal carcinoma were enrolled. Lactate concentration was quantified from freshly excised whole tumours with double quantum filtered (DQF) magnetic resonance spectroscopy (MRS), and Nottingham Prognostic Index (NPI), LDH-A and proliferative marker Ki-67 were assessed histologically.ResultsThere was a significantly higher lactate concentration (t = 2.2224, p = 0.0349) in grade III (7.7 ± 2.9 mM) than in grade II (5.5 ± 2.4 mM). Lactate concentration was correlated with NPI (ρ = 0.3618, p = 0.0495), but not with Ki-67 (ρ = 0.3041, p = 0.1023) or tumour size (r = 0.1716, p = 0.3645). Lactate concentration was negatively correlated with LDH-A (ρ = −0.3734, p = 0.0421).ConclusionOur results showed that lactate concentration in whole breast tumour from DQF MRS is sensitive to tumour grades and patient prognosis.
Highlights
Precision medicine in breast cancer demands markers sensitive to early treatment response
Lactate was measurable in all spectra, defined as Cramér-Rao lower bound (CRLB) of the fit below 30%
In this work, we found lactate concentration was significantly higher in grade III breast tumours compared to grade II
Summary
Precision medicine in breast cancer demands markers sensitive to early treatment response. The 10-year survival rate of breast cancer has improved substantially from 40.1 to 78.4% in the last 40 years,[1] primarily resulting from advancement in chemotherapy[2] and targeted endocrine modulation.[3] Non-responding patients are exposed to side effects and possible life threatening complications,[4] and may experience disease progression during treatment and delayed surgery,[5] demanding an early response marker beyond crude tumour size. The accumulation of lactate generates an acidic environment suppressing normal immunological functions while providing fuel to tumour cells, resulting in accelerated local invasion.[8] The inhibition of lactate production induces tumour regression in cancer xenografts, underpinning the role of lactate concentration as a response marker.[9]
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