Changes in blood flow and metabolism in locally advanced breast cancer treated with neoadjuvant chemotherapy.
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 performed serial measurements of blood flow and glucose metabolism in LABC patients over the course of neoadjuvant chemotherapy and compared measurements with response.


METHODS
Thirty-five patients with newly diagnosed LABC underwent (18)F-FDG and (15)O-water PET imaging before therapy and after 2 mo of chemotherapy. Tumor metabolism was estimated from graphical analysis of dynamic (18)F-FDG studies and was expressed as the metabolic rate of (18)F-FDG (MRFDG). Blood flow was estimated from dynamic images after bolus (15)O-water injection using a 1-compartment model. Metabolism and blood flow data were analyzed with and without partial-volume corrections to account for changes in tumor size over the course of therapy. Changes in tumor blood flow and metabolism were compared with response to chemotherapy and with patient survival.


RESULTS
For all patients, the mean MRFDG after 2 mo of chemotherapy decreased by 54% and the mean blood flow by 21%. Responders showed a greater decline in MRFDG than did nonresponders; however, the difference was of borderline significance (P = 0.05) after correction for partial-volume effects. Patients who responded had a decline in tumor blood flow, whereas nonresponders had an average increase (-32% vs. +48%, P < 0.005); the difference between responders and nonresponders remained significant after partial-volume correction (P < 0.01). There was also a statistically significant association between the pathologic degree of response and the percentage change in blood flow at 2 mo with and without partial-volume correction; this was not the case for MRFDG. The change in blood flow after 2 mo of therapy predicted disease-free and overall survival.


CONCLUSIONS
Although both resistant and responsive LABC tumors have an average decline in MRFDG over the course of chemotherapy, resistant tumors have an average increase in blood flow. Patients whose tumors fail to have a decline in blood flow after 2 mo of therapy have poorer disease-free and overall survival. Further investigations are needed to elucidate the tumor biology underlying these findings.
Mankoff
David A
DA
Division of Nuclear Medicine, University of Washington, Seattle, Washington 98195, USA. dam@u.washington.edu
Dunnwald
Lisa K
LK
Gralow
Julie R
JR
Ellis
Georgiana K
GK
Schubert
Erin K
EK
Tseng
Jeffrey
J
Lawton
Thomas J
TJ
Linden
Hannah M
HM
Livingston
Robert B
RB
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000098:blood supply* / Q000188:drug therapy / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008875:Middle Aged; D012039:Regional Blood Flow; D014055:Tomography, Emission-Computed
D019788:Fluorodeoxyglucose F18