Imaging tumor hypoxia with BOLD MRI in primary breast cancer.

Abstract

e13526 Background: Blood oxygenation level dependent (BOLD) MRI provides a noninvasive means of assessing in vivo tumor oxygenation by relying on endogenous deoxyhemoglobin as a contrast agent. Higher apparent relaxation rates (R2*) represent a more hypoxic environment. However BOLD MRI is underexplored in breast cancer (BC) and histologic correlates and chemotherapy response in relation to R2* are unknown. Methods: 83 pts with primary BC were selected to undergo dynamic contrast enhanced (DCE) and BOLD MRI before and after 2 cycles of neoadjuvant chemotherapy (NAC). Pts with diffusely infiltrating, invasive lobular (ILC) or necrotic tumors were excluded due to confounding R2* values. DCE MRI T1 and T2w parameters (Ktrans, ve, kep, IAUGC60, relative blood flow (rBF) and volume (rBV), MTT) and R2* were derived. Relationships between baseline characteristics (grade, size, ER/PR/HER2), imaging parameters and R2* were examined; continuous variables using Spearman's rank correlation (ρ) and discrete variables with the Mann-Whitney U test. Baseline R2* and R2* changes with NAC were correlated with final pathologic response using paired t-testing. Results: 31 pts (median age 44; T2-4, N0-1, M0) were available for baseline and 27 for response assessment. 12 did not undergo both MRIs, 1 had only nodal disease visible, images for 2 were not analyzable and another 4 did not undergo second MRIs. 37 had either ILC, ill-defined and/or necrotic tumors. 15 pts received anthracycline based and 12 docetaxel NAC. Baseline R2* did not correlate with histologic parameters, size, or response. Inverse correlations were observed between rBF/rBV and R2* (p=−0.48, p=0.013; p=−0.44, p=0.024) which disappeared with NAC (p=−0.28, p=0.196; p=−0.31, p=0.155). R2* increases were observed with NAC (34.8 s-1 vs. -31.1 s-1, p=0.006) with larger increases correlating with final pathologic response (36.5 s-1 vs. 31.7 s-1, p=0.025). Conclusions: The relationship between R2* and rBV/BF confirms that R2* in treatment naÏve BC relates to blood rather than tumor oxygenation. However with the loss of this relationship after NAC, R2* becomes a marker of tumor hypoxia. The R2* increases seen with NAC suggest that tumors become hypoxic with NAC particularly in responders. BOLD MRI may help select pts suitable for hypoxia modifying agents. No significant financial relationships to disclose.