Prospective early response imaging biomarker for neoadjuvant breast cancer chemotherapy.
OBJECTIVE
The American Cancer Society estimates that in 2006, 212,920 women will be diagnosed with breast cancer and that 40,970 women will die from the disease. The development of more efficacious chemotherapies has improved outcomes, but the rapid assessment of clinical benefit from these agents remains challenging. In breast cancer patients receiving neoadjuvant chemotherapy, treatment response is traditionally assessed by physical examination and volumetric-based measurements, which are subjective and require macroscopic changes in tumor morphology. In this study, we evaluate the feasibility of using diffusion magnetic resonance imaging (MRI) as a reliable and quantitative measure for the early assessment of response in a breast cancer model.


METHODS
Mice implanted with human breast cancer (MX-1) were treated with cyclophosphamide and evaluated using diffusion MRI and growth kinetics. Histologic analyses using terminal nucleotidyl transferase-mediated nick end labeling and H&E were done on tumor samples for correlation with imaging results.


RESULTS
Cyclophosphamide treatment resulted in a significant reduction in tumor volumes compared with controls. The mean apparent diffusion change for treated tumors at days 4 and 7 posttreatment was 44 +/- 5% and 94 +/- 7%, respectively, which was statistically greater (P < 0.05) than the control tumors at the same time intervals. The median time-to-progression for control and treated groups was 11 and 32 days, respectively (P < 0.05).


CONCLUSIONS
Diffusion MRI was shown to detect early changes in the tumor microenvironment, which correlated with standard measures of tumor response as well as overall outcome. Moreover, these findings show the feasibility of using diffusion MRI for assessing treatment response of a breast tumor model in a neoadjuvant setting.
Lee
Kuei C
KC
Department of Radiology, Center for Molecular Imaging, University of Michigan Medical School, Biomedical Sciences Research Building, 109 Zina Pitcher Place, Ann Arbor, MI 48109, USA.
Moffat
Bradford A
BA
Schott
Anne F
AF
Layman
Rachel
R
Ellingworth
Steven
S
Juliar
Rebecca
R
Khan
Amjad P
AP
Helvie
Mark
M
Meyer
Charles R
CR
Chenevert
Thomas L
TL
Rehemtulla
Alnawaz
A
Ross
Brian D
BD
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000628:therapy*; D003520:Cyclophosphamide / Q000494:pharmacology; D004058:Diffusion; D018450:Disease Progression; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D015674:Mammary Neoplasms, Animal / Q000175:diagnosis / Q000628:therapy; D051379:Mice; D009368:Neoplasm Transplantation; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D003520:Cyclophosphamide