Breast cancer and non-malignant breast data: Quantification by FPT - Signal Processing in MRS with Biomedical Applications - page 309

has been found that choline is often undetected in small tumors that are then
misclassified as benign [116]. Choline also appears in normal breast during
lactation, although in the latter, a lactose resonance at 3.8 ppm is typically
also seen [393]. It should, however, also be pointed out that breast cancer
can coexist with lactation as well as with pregnancy, and these malignancies
are often detected late [396]. Moreover, various authors have used different
cutpoints for total choline concentrations to define malignant versus benign
breast tissue. This renders any attempt at standardization highly precarious.
10.3 Insights for breast cancer diagnostics from in vitro
MRS
As opposed to in vivo MRS breast examinations based mainly upon one com
posite spectral entity (the total choline peak), the high resolution of in vitro
MRS applied to extracted specimens provides a much greater insight into the
metabolic activity of malignant breast tissue. Analysis of excised breast can
cers shows that the composite choline peak contains phosphocholine (PCho),
glycerophosphocholine (GPC), betaine, analogous compounds containing the
ethanolamine head group and taurine, as well as free choline itself [397].
Using tracer kinetics and 13 C NMR and 31 P NMR to examine the biochemi
cal mechanisms underlying the high levels of watersoluble choline metabolites
seen in breast cancer, KatzBrull et al. [397] identified two nonintersecting
pathways: phosphorylation and oxidation of choline, that were augmented
with malignant transformation of mammary cells, with increased synthesis of
phosphocholine and betaine, and suppression of cholinederived ether lipids.
Gribbestad et al. [395] conducted an in vitro proton MRS study in which
they compared fourteen extracts of cancerous breast tissue and one fibroade
noma to noninvolved breast from the same group of patients. We subse
quently performed logistic regression analysis of these data to determine the
sensitivity and specificity of individual metabolite concentrations for identi
fying breast cancer [21, 22, 25]. We found that only lactate showed 100%
diagnostic accuracy both with and without the fibroadenoma. The diagnostic
accuracy of total choline 2 was marginally lower than several of the individual
metabolites, including some of its own constituents. Paired ttest analyses re
vealed a significant difference in all metabolite concentrations when comparing
noninfiltrated and malignant breast tissue (always higher in the latter).
In the study from Ref. [395] glycerophosphocholine, phosphocholine, phos
phoethanolamine, total choline and lactate were elevated, as well, in the fi
2 The composite or total choline peak is comprised of choline (3.21 ppm), phosphocholine
(3.22 ppm) and glycerophosphocholine (3.23 ppm) for in vitro proton MRS.