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ABSTRACT: Blood Flow and Metabolism in Locally Advanced Breast
Cancer: Relationship to Response to Therapy
Locally advanced breast cancer (LABC) is commonly treated with
neoadjuvant chemotherapy followed by definitive surgery. The
factors influencing the response of LABC to presurgical chemotherapy
are incompletely understood.
To characterize in vivo tumor biology
in patients with LABC, we measured pretherapy blood flow and
glucose metabolism in LABC, compared measurements with clinical
and pathologic parameters, and examined blood flow and response
to subsequent neoadjuvant chemotherapy.
Methods: Thirty-seven
patients with newly diagnosed LABC underwent 18F-FDG and 15O-water
PET imaging. Thirty-one of these patients underwent neoadjuvant
chemotherapy, and response was evaluated by serial measurements
of tumor size and pathologic examination after definitive surgery
after chemotherapy.
Tumor metabolism was estimated from graphic
analysis of dynamic 18F-FDG studies and was expressed as the
metabolic rate of 18F-FDG (MRFDG). Blood flow was estimated from
dynamic images after bolus 15O-water injection using a 1-compartment
model. Tumor blood flow and metabolism were compared with clinical
and pathologic parameters and with response to chemotherapy.
Results: Both blood flow and metabolism were significantly higher
in tumor than in normal breast.
Tumor blood flow and metabolism
were correlated but highly variable. There were weak associations
of metabolism with patient age and tumor grade and of blood flow
with estrogen receptor status. There was a statistically significant
trend for patients with a high MRFDG to have a poorer response
to therapy (P = 0.001). Response was not significantly correlated
with any other parameters.
A low ratio of MRFDG to blood flow
was the best predictor of macroscopic complete response (CR)
(P = 0.02 vs. non-CR). Preliminary analysis of patient follow-up
showed the ratio of MRFDG to blood flow to also be predictive
of disease-free survival.
Conclusion: Despite uniformly large
tumor size, blood flow and metabolism in LABC are highly variable.
High glucose metabolism predicts a poor response to neoadjuvant
chemotherapy, and low MRFDG relative to blood flow is a predictor
of CR.
Further work is needed to elucidate the biologic mechanisms
underlying these findings.
[04/12/2002; Journal of Nuclear Medicine]
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